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Mo X, Men Z, Gao L, Gao Y, Yao T, Liu Y, Yuan Y, Xue T, Wang F, Wang S, Wang K, Liang X, Feng Y. Immunogenicity persistence after four intramuscular triple-dose or standard-dose hepatitis B vaccine in patients receiving methadone maintenance treatment: A 1-year follow-up study in China. Hum Vaccin Immunother 2025; 21:2447108. [PMID: 39819251 DOI: 10.1080/21645515.2024.2447108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 12/09/2024] [Accepted: 12/22/2024] [Indexed: 01/19/2025] Open
Abstract
CLINICAL TRIAL REGISTRATION ClinicalTrials.gov (NCT03962816).https://clinicaltrials.gov/ct2/show/NCT03962816.
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Affiliation(s)
- Xinyuan Mo
- School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, China
- Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, Shanxi, China
- Key Laboratory of Coal Environmental Pathogenicity and Prevention (Shanxi Medical University) Ministry of Education, Taiyuan, Shanxi, China
| | - Zhaoyue Men
- School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, China
- Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, Shanxi, China
- Key Laboratory of Coal Environmental Pathogenicity and Prevention (Shanxi Medical University) Ministry of Education, Taiyuan, Shanxi, China
| | - Linying Gao
- School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Yizhuo Gao
- School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Tian Yao
- Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, Shanxi, China
- First Hospital/First Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Yuan Liu
- Methadone Maintenance Treatment Clinic, Compulsory Isolation Drug Rehabilitation Center, Taiyuan, Shanxi, China
| | - Yuan Yuan
- Methadone Maintenance Treatment Clinic, 109 hospital, Taiyuan, Shanxi, China
| | - Tongchuan Xue
- Xinghualing District Methadone Maintenance Treatment Clinic, Taiyuan, Shanxi, China
| | - Fuzhen Wang
- Chinese Center for Disease Control and Prevention, Beijing, China
| | - Suping Wang
- School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, China
- Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, Shanxi, China
- Key Laboratory of Coal Environmental Pathogenicity and Prevention (Shanxi Medical University) Ministry of Education, Taiyuan, Shanxi, China
| | - Keke Wang
- First Hospital/First Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Xiaofeng Liang
- Institute of Vaccine Industry, Institute of Disease Control and Prevention, Jinan University, Guangzhou, Guangdong, China
- Chinese Preventive Medicine Association, Beijing, China
| | - Yongliang Feng
- School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, China
- Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, Shanxi, China
- Key Laboratory of Coal Environmental Pathogenicity and Prevention (Shanxi Medical University) Ministry of Education, Taiyuan, Shanxi, China
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Wu Y, Tang G, Wen J, Wan Y, Wang Y, Li L. Serum hepatitis B virus RNA in low-level viremia of chronic hepatitis B: clinical features and association with virological response. Virol J 2025; 22:132. [PMID: 40325459 PMCID: PMC12054217 DOI: 10.1186/s12985-025-02712-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 03/21/2025] [Indexed: 05/07/2025] Open
Abstract
BACKGROUND The role of hepatitis B virus (HBV) RNA in the management of patients with chronic hepatitis B (CHB) experienced with low-level viremia (LLV) remains poorly defined. This study was designed to evaluate the prognostic utility of serum HBV RNA as a biomarker for predicting treatment outcomes in this population. METHODS A retrospective cohort analysis was conducted on 117 pediatric patients with LLV (mean age: 13.14 years; 34% female) treated with continuous entecavir (ConT) or modified regimens (switching to or combining with tenofovir disoproxil fumarate) for ≥ 120 weeks. Virological response was defined as HBV DNA < 10 IU/mL at week 120. RESULTS No significant baseline differences existed between ConT and modified regimen groups. Compared to ConT, modified regimens achieved greater reductions in serum HBV DNA, HBV RNA, and quantitative HBsAg, with higher cumulative undetectable rates at week 120 (HBV DNA: ≥ 80.0%; HBV RNA: ≥ 54.8%; P < 0.05). Notably, qHBsAg levels remained elevated in most patients, with only 3 individuals achieving undetectable levels (< 0.05 IU/mL). Multivariate analysis identified higher HBV RNA levels at week 48 as an independent risk factor for non-virological response (adjusted odds ratio: 5.86; 95% confidence interval: 1.40-24.62; P = 0.016). Although HBV RNA alone was less predictive than HBV DNA (area under the receiver operating characteristic curve [AUC]: 0.76 vs. 0.80; P = 0.459), combining both markers improved prediction accuracy (AUC: 0.82; P < 0.05 vs. single markers). CONCLUSIONS In children with LLV, serum HBV RNA level is an independent risk factor for non-virological response and may serve as a complementary biomarker to HBV DNA for guiding antiviral therapy adjustments.
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Affiliation(s)
- Yongbin Wu
- Department of Laboratory Medicine, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin, China.
| | - Guifang Tang
- Department of Infectious Diseases, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin, China
| | - Jian Wen
- Department of Hematology, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin, China
| | - Ying Wan
- Department of Laboratory Medicine, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin, China
| | - Yufei Wang
- Department of Clinical Diagnosis, Laboratory of Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Ling Li
- School of Basic Medical Science, Southern Medical University, Guangzhou, China
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Yang JL, Yang J, Fang RF, Sai WL, Yao DF, Yao M. Hypoxia upregulates hepatic angiopoietin-2 transcription to promote the progression of hepatocellular carcinoma. World J Hepatol 2024; 16:1480-1492. [DOI: 10.4254/wjh.v16.i12.1480] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Revised: 08/22/2024] [Accepted: 09/13/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND Angiopoietin-2 (Ang-2) level is related to hepatocellular carcinoma (HCC) progression. However, the dynamic expression and regulatory mechanism of Ang-2 remain unclear.
AIM To investigate Ang-2 levels in chronic liver diseases and validate early monitoring value with a dynamic model in hepatocarcinogenesis.
METHODS Sprague-Dawley rats in hepatocarcinogenesis were induced with diet 2-fluorenylacet-amide, and grouped based on liver histopathology by hematoxylin and eosin staining. Differently expressed genes or Ang-2 mRNA in livers were analyzed by whole-genome microarray. Ang-2 levels in chronic liver diseases were detected by an enzyme-linked immunosorbent assay.
RESULTS Clinical observation reveled that the circulating levels of Ang-2 and hypoxia-inducible factor-1α (HIF-1α) in patients with chronic liver diseases were progressively increased from benign to HCC (P < 0.001). Dynamic model validated that the up-regulated Ang-2 in liver and blood was positively correlated with HIF-1α in hepatocarcinogenesis (P < 0.001). Mechanistically, Ang-2 was regulated by HIF-1α. When specific HIF-1α- microRNAs transfected into HCC cells, the cell proliferation significantly inhibited, HIF-1α and Ang-2 down-regulated, and also affected epithelial-mesenchymal transition via increasing E-cadherin to block cell invasion or migration with reducing of snail, twist and vimentin.
CONCLUSION Hypoxia-induced Ang-2 up-regulating expression might serve as a sensitive early monitoring biomarker for hepatocarcinogenesis or HCC metastasis.
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Affiliation(s)
- Jun-Ling Yang
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University and Department of Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Jie Yang
- Department of Biology, Life Science School of Nantong University, Nantong 226009, Jiangsu Province, China
| | - Rong-Fei Fang
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Wen-Li Sai
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University and Department of Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Deng-Fu Yao
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University and Department of Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Min Yao
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University and Department of Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
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Yu YB, Fu XJ, Xu GF, Niu LY, Duan RN, Yao J, Zhao NH. Effects of nocturnal snacks on body composition in patients with liver cirrhosis. World J Hepatol 2024; 16:1458-1467. [DOI: 10.4254/wjh.v16.i12.1458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Revised: 08/10/2024] [Accepted: 08/19/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND Patients with liver cirrhosis are universally malnourished and the nocturnal snacks intervention is the currently recommended nutritional intervention for patients with liver cirrhosis. Body composition is an important indicator for the assessment of nutritional conditions. We investigated the effects of nocturnal snacks (200 kcal/day) for 3 months on body composition in patients with liver cirrhosis.
AIM To investigate the effect of nocturnal snacks on body composition in patients with cirrhosis.
METHODS Seventy patients with liver cirrhosis and 30 healthy controls were enrolled, and differences in body composition were detected using InBody 720, a body composition analyzer. The patients were further randomized into a normal diet group (three meals a day) and nocturnal snacks group (three meals a day + nocturnal snacks). The effect of nocturnal snacks on the body composition of patients with cirrhosis was assessed after 3 months of intervention.
RESULTS Body fat mass (BFM), skeletal muscle mass (SMM), fat free mass, visceral fat area (VFA), and body cell mass (BCM) were significantly lower in the liver cirrhosis patients than in the healthy controls. After 3 months’ intervention, BFM, VFA and BCM were significantly higher in the nocturnal snacks group than in the normal diet group, with no significant differences in total caloric intake and daily activity. However, there was no significant difference in SMM between the nocturnal snacks and normal diet groups.
CONCLUSION Long-term nocturnal snacks may improve body composition indices such as BFM, VFA and BCM in patients with cirrhosis. However, the improvement was minor for SMM.
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Affiliation(s)
- Yong-Bo Yu
- Department of Neurology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan 030032, Shanxi Province, China
| | - Xiu-Juan Fu
- Department of Gastroenterology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan 030032, Shanxi Province, China
| | - Guo-Fen Xu
- Department of Gastroenterology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan 030032, Shanxi Province, China
| | - Ling-Yun Niu
- Department of Gastroenterology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan 030032, Shanxi Province, China
| | - Ruo-Nan Duan
- Department of Nutrition, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan 030032, Shanxi Province, China
| | - Jia Yao
- Department of Gastroenterology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan 030032, Shanxi Province, China
| | - Ning-Hui Zhao
- Department of Gastroenterology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan 030032, Shanxi Province, China
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Li HD, Liu YN, Wu S, Quan XF, Wang XY, Xiang TD, Li SM, Xu L, Wang T, Wang H, Zheng X. Influence of nonalcoholic fatty liver disease on the therapeutic effect of nucleoside (acid) analogs for hepatitis B virus. World J Hepatol 2024; 16:1395-1406. [DOI: 10.4254/wjh.v16.i12.1395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Revised: 10/02/2024] [Accepted: 10/29/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND The effect of nonalcoholic fatty liver disease (NAFLD) on the efficacy of nucleoside analogues (NAs) in antiviral therapy for patients with chronic hepatitis B (CHB) remains controversial.
AIM To investigate the influence of NAFLD on virological response in CHB patients undergoing NAs treatment.
METHODS Logistic regression analysis was conducted on a cohort of 465 CHB patients from two hospitals to determine whether NAFLD was a risk factor for adverse reactions to NAs. CHB patients were followed up for more than 28 months after initial antiviral treatment, and further validation was performed using different viral load populations.
RESULTS NAFLD was identified as an independent risk factor for partial virological response following antiviral therapy with NAs (odds ratio = 1.777, P = 0.017). In our subsequent analysis focusing on CHB patients with high viral load, the NAFLD group exhibited significantly longer virus shedding time and lower proportion of the complete virological response compared with the non-NAFLD group (16.8 ± 6.1 vs 13.0 ± 6.8, P < 0.05). During the 24-month period of antiviral treatment with NAs, hepatitis B virus (HBV) DNA levels decreased slowly in the NAFLD group, and the negative conversion rate of HBV was notably lower than that observed in non-NAFLD group (P = 0.001). Similar results were obtained when analyzing patients with low baseline HBV viral load within the NAFLD group.
CONCLUSION Coexistence of NAFLD may diminish virological response among CHB patients receiving antiviral treatment with NAs.
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Affiliation(s)
- Hua-Dong Li
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
- Department of Infectious Diseases, Wuhan Jinyintan Hospital, Wuhan 430023, Hubei Province, China
| | - Ya-Nan Liu
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Shuang Wu
- Department of Infectious Diseases, Wuhan Jinyintan Hospital, Wuhan 430023, Hubei Province, China
| | - Xu-Feng Quan
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Xiao-Yan Wang
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Tian-Dan Xiang
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Shu-Meng Li
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Ling Xu
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Tong Wang
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Hua Wang
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Xin Zheng
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
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Lu R, Zhang M, Liu ZH, Hao M, Tian Y, Li M, Wu FP, Wang WJ, Shi JJ, Zhang X, Jia XL, Jiang ZC, Li XM, Xu GH, Li YP, Dang SS. Recurrence and influencing factors of hepatitis B surface antigen seroclearance induced by peginterferon alpha-based regimens. World J Gastroenterol 2024; 30:4725-4737. [PMID: 39610775 PMCID: PMC11580604 DOI: 10.3748/wjg.v30.i44.4725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 09/27/2024] [Accepted: 10/28/2024] [Indexed: 11/12/2024] Open
Abstract
BACKGROUND The long-term stability of hepatitis B surface antigen (HBsAg) seroclearance following peginterferon alpha (peg-IFN-α)-based therapy has not been extensively studied, leaving the full potential and limitations of this strategy unclear. AIM To assess HBsAg recurrence after seroclearance achieved by peg-IFN-α regimens. METHODS This prospective, multicenter, observational study was conducted from November 2015 to June 2021 at three Chinese hospitals: The Second Affiliated Hospital of Xi'an Jiaotong University, Ankang Central Hospital, and The Affiliated Hospital of Yan'an University. Participants who achieved HBsAg seroclearance following peg-IFN-α-based treatments were monitored every 4-12 weeks post-treatment for hepatitis B virus (HBV) markers, HBV DNA, and liver function. The primary outcome was HBV recurrence, defined as the reemergence of HBsAg, HBV DNA, or both, at least twice within 4-8 weeks of follow-up. RESULTS In total, 121 patients who achieved HBsAg seroclearance were enrolled. After a median follow-up of 84.0 (48.0, 132.0) weeks, four subjects were lost to follow-up. HBsAg recurrence was detected in 16 patients. The cumulative HBsAg recurrence rate in the intention-to-treat population was 15.2%. Multivariate logistic regression analysis demonstrated that consolidation time < 12 weeks [odds ratio (OR) = 28.044, 95%CI: 4.525-173.791] and hepatitis B surface antibody disappearance during follow-up (OR = 46.445, 95%CI: 2.571-838.957) were strong predictors of HBsAg recurrence. HBV DNA positivity and decompensation of liver cirrhosis and hepatocellular carcinoma were not observed. CONCLUSION HBsAg seroclearance following peg-IFN-α treatment was durable over 84 weeks of follow-up with a cumulative recurrence rate of 15.2%.
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Affiliation(s)
- Rui Lu
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
| | - Meng Zhang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
| | - Zi-Han Liu
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
| | - Miao Hao
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
| | - Yan Tian
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
| | - Mei Li
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
| | - Feng-Ping Wu
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
| | - Wen-Jun Wang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
| | - Juan-Juan Shi
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
| | - Xin Zhang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
| | - Xiao-Li Jia
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
| | - Zi-Cheng Jiang
- Department of Infectious Diseases, Ankang Central Hospital, Ankang 725000, Shaanxi Province, China
| | - Xue-Mei Li
- Department of Infectious Diseases, Ankang Central Hospital, Ankang 725000, Shaanxi Province, China
| | - Guang-Hua Xu
- Department of Infectious Diseases, The Affiliated Hospital of Yan’an University, Yan’an 716000, Shaanxi Province, China
| | - Ya-Ping Li
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
| | - Shuang-Suo Dang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
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Xu W, Luo Q, Zhang Y, Xie C, Peng L. A case report: cccDNA and pgRNA remain positive in liver tissue in a chronic hepatitis B patient with functional cure. Front Med (Lausanne) 2024; 11:1427043. [PMID: 39534217 PMCID: PMC11554451 DOI: 10.3389/fmed.2024.1427043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Accepted: 10/11/2024] [Indexed: 11/16/2024] Open
Abstract
Hepatitis B surface antigen (HBsAg) seroclearance is recommended as the ideal endpoint for nucleos(t)ide analog (NA) treatments. Functional cure of chronic hepatitis B (CHB) is defined as having undetectable serum hepatitis B virus (HBV) deoxyribonucleic acid and serum HBsAg. We report a functional cure case of CHB with a family history of hepatocellular carcinoma (HCC) after long-term NA therapy. Despite achieving functional cure for over 7 years, both HBV covalently closed circular deoxyribonucleic acid (cccDNA) and pregenomic ribonucleic acid (pgRNA) remain positive in the liver tissue of the patient, indicating that a sterilizing cure has not been achieved. This case highlights the importance of active surveillance of HBV cccDNA and pgRNA for sterilizing the cure and risk of HCC.
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Affiliation(s)
- Wenxiong Xu
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Qiumin Luo
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yeqiong Zhang
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Chan Xie
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Liang Peng
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, China
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Han K, Wang J, Song X, Kang L, Lin J, Hu Q, Sun W, Gao Y. Development and validation of a nomogram for predicting advanced liver fibrosis in patients with chronic hepatitis B. Front Mol Biosci 2024; 11:1452841. [PMID: 39286781 PMCID: PMC11403247 DOI: 10.3389/fmolb.2024.1452841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 08/13/2024] [Indexed: 09/19/2024] Open
Abstract
Background The progression of chronic hepatitis B (CHB) to liver fibrosis and even cirrhosis is often unknown to patients, but noninvasive markers capable of effectively identifying advanced liver fibrosis remains absent. Objective Based on the results of liver biopsy, we aimed to construct a new nomogram to validate the stage of liver fibrosis in CHB patients by the basic information of CHB patients and routine laboratory tests. Methods Patients with CHB diagnosed for the first time in the First Affiliated Hospital of Anhui Medical University from 2010 to 2018 were selected, and their basic information, laboratory tests and liver biopsy information were collected. Eventually, 974 patients were enrolled in the study, while all patients were randomized into a training cohort (n = 732) and an internal validation cohort (n = 242) according to a 3:1 ratio. In the training cohort, least absolute shrinkage and selection operator (Lasso) regression were used for predictor variable screening, and binary logistic regression analysis was used to build the diagnostic model, which was ultimately presented as a nomogram. The predictive accuracy of the nomograms was analyzed by running operating characteristic curve (ROC) to calculate area under curve (AUC), and the calibration was evaluated. Decision curve analysis (DCA) was used to determine patient benefit. In addition, we validated the built models with internal as well as external cohort (n = 771), respectively. Results Ultimately, the training cohort, the internal validation cohort, and the external validation cohort contained sample sizes of 188, 53, and 149, respectively, for advanced liver fibrosis. Gender, albumin (Alb), globulin (Glb), platelets (PLT), alkaline phosphatase (AKP), glutamyl transpeptidase (GGT), and prothrombin time (PT) were screened as independent predictors. Compared with the aminotransferase-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4), and King's score, the model in the training cohort (AUC = 0.834, 95% CI 0.800-0.868, p < 0.05) and internal validation cohort (AUC = 0.804, 95% CI 0.742-0.866, p < 0.05) showed the best discrimination and the best predictive performance. In addition, DCA showed that the clinical benefit of the nomogram was superior to the APRI, FIB-4 and King's scores in all cohorts. Conclusion This study constructed a validated nomogram model with predictors screened from clinical variables which could be easily used for the diagnosis of advanced liver fibrosis in CHB patients.
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Affiliation(s)
- Kexing Han
- The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Jianfeng Wang
- The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Xizhen Song
- The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Luyang Kang
- The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Junjie Lin
- The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Qinggang Hu
- The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Weijie Sun
- The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yufeng Gao
- The First Affiliated Hospital of Anhui Medical University, Hefei, China
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Wu L, Lai J, Luo Q, Zhang Y, Lin C, Xie D, Chen Y, Deng H, Gao Z, Peng L, Xu W. Long-term hepatitis B surface antigen kinetics after nucleos(t)ide analog discontinuation in patients with noncirrhotic chronic hepatitis B. LIVER RESEARCH 2024; 8:179-187. [PMID: 39957751 PMCID: PMC11771267 DOI: 10.1016/j.livres.2024.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 03/10/2024] [Accepted: 07/02/2024] [Indexed: 02/18/2025]
Abstract
Background and aim Few studies have reported hepatitis B surface antigen (HBsAg) kinetics after nucleos(t)ide analog (NA) discontinuation in patients with noncirrhotic chronic hepatitis B (CHB). The study specifically investigated long-term HBsAg kinetics after NA discontinuation. Methods Between January 2014 to January 2024, this study prospectively enrolled 106 outpatients with noncirrhotic CHB who met the discontinuation criteria after NA consolidation treatment. Demographic, clinical, and laboratory data were collected and analyzed after NA discontinuation. Results Ninety-six patients who finished 5 years of follow-up were included. HBsAg remained undetectable in 29 patients with end of treatment (EOT) HBsAg negativity. Among 67 patients with EOT HBsAg positivity, HBsAg seroclearance occurred in 12 (17.9%) patients with an estimated annual incidence of HBsAg seroclearance of 3.6%. Patients with EOT HBsAg levels of ≤1000 IU/mL had a higher HBsAg seroclearance rate than those with EOT HBsAg levels of >1000 IU/mL (33.3% vs. 5.4%). The proportion of patients with HBsAg ≤1000 IU/mL increased during follow-up. Logistic regression analysis indicated that the EOT HBsAg level was an independent factor for HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL. The optimal EOT HBsAg cutoff for both HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL was 359 IU/mL. Conclusions Patients with EOT HBsAg negativity experienced no relapse and maintained HBsAg seroclearance during 5 years of follow-up after NA discontinuation. A higher HBsAg seroclearance rate can be obtained in patients with EOT HBsAg levels of ≤1000 IU/mL during 5 years of follow-up after NA discontinuation. Close monitoring and proper NA retreatment are recommended to guarantee the safety of NA discontinuation. Clinical trial number Clinicaltrials.gov number NCT02883647.
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Affiliation(s)
- Lina Wu
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Jiadi Lai
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Qiumin Luo
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yeqiong Zhang
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Chaoshuang Lin
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Dongying Xie
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Youming Chen
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Hong Deng
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Zhiliang Gao
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Liang Peng
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Wenxiong Xu
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
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10
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Liu X, Lu Y, Zhou W, Peng T, Zhou J, Bi H, Xia F, Chen X. Chinese Multidisciplinary Expert Consensus on Immune Checkpoint Inhibitor-Based Combination Therapy for Hepatocellular Carcinoma (2023 Edition). Liver Cancer 2024; 13:355-375. [PMID: 39114757 PMCID: PMC11305662 DOI: 10.1159/000535496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Accepted: 11/10/2023] [Indexed: 08/10/2024] Open
Abstract
Background Immune checkpoint inhibitor (ICI)-based combination therapy modalities for hepatocellular carcinoma (HCC) have achieved significant efficacy in clinical research and practice and have become the mainstay for the treatment of unresectable HCC. Summary To better help clinicians use combination immunotherapy drugs and regimens rationally, effectively, and safely, the editorial board facilitated a discussion with multidisciplinary experts in the field, adopted the "Delphi" consensus formation method, and finally revised and completed the "Chinese Multidisciplinary Expert Consensus on the Immune Checkpoint Inhibitors (ICIs)-Based Combination Therapy for Hepatocellular Carcinoma (2023 Edition)" on the basis of the 2021 edition. Key Messages This consensus primarily focuses on the principles and methods of clinical practice of combination therapy based on ICIs, aiming to summarize the recommendations for clinical application based on the latest research and expert experience and provide application guidance for clinicians.
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Affiliation(s)
- Xiufeng Liu
- Department of Medical Oncology of PLA Cancer Center, Jinling Hospital, Nanjing, China
| | - Yinying Lu
- Comprehensive Liver Cancer Center, 5th Medical Center of PLA General Hospital, Beijing, China
| | - Weiping Zhou
- Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Tao Peng
- Hepatobiliary Surgery Department, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Jie Zhou
- Division of Hepatobiliopancreatic Surgery and Liver Transplantation, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Huaqiang Bi
- Department of Hepatobiliary Surgery, The First Hospital Affiliated to Army Medical University, Chongqing, China
| | - Feng Xia
- Department of Hepatobiliary Surgery, The First Hospital Affiliated to Army Medical University, Chongqing, China
| | - Xiaoping Chen
- Department of Hepatobiliary Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
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Li YP, Liu CR, He L, Dang SS. Hepatitis B cure: Current situation and prospects. World J Hepatol 2024; 16:900-911. [PMID: 38948438 PMCID: PMC11212658 DOI: 10.4254/wjh.v16.i6.900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Revised: 05/05/2024] [Accepted: 06/03/2024] [Indexed: 06/20/2024] Open
Abstract
Achievement of a 'clinical cure' in chronic hepatitis B (CHB) implies sustained virological suppression and immunological control over the infection, which is the ideal treatment goal according to domestic and international CHB management guidelines. Clinical practice has shown encouraging results for specific patient cohorts using tailored treatment regimens. These regimens incorporate either nucleos(t)ide analogs, immunomodulatory agents such as pegylated interferon α, or a strategic combination of both, sequentially or concurrently administered. Despite these advancements in the clinical handling of hepatitis B, achieving a clinical cure remains elusive for a considerable subset of patients due to the number of challenges that preclude the realization of optimal treatment outcomes. These include, but are not limited to, the emergence of antiviral resistance, incomplete immune recovery, and the persistence of covalently closed circular DNA. Moreover, the variance in response to interferon therapy and the lack of definitive biomarkers for treatment cessation also contribute to the complexity of achieving a clinical cure. This article briefly overviews the current research progress and existing issues in pursuing a clinical cure for hepatitis B.
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Affiliation(s)
- Ya-Ping Li
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
| | - Chen-Rui Liu
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
| | - Ling He
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
| | - Shuang-Suo Dang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
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12
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Hou J, Ning Q, Duan Z, Chen Y, Xie Q, Zhang L, Wu S, Tang H, Li J, Lin F, Yang Y, Gong G, Luo Y, Xie S, Wang H, Mateo R, Yazdi T, Abramov F, Yee LJ, Flaherty J, Chen C, Huang Y, Zhang M, Jia J. Five-year Treatment with Tenofovir Alafenamide Achieves High Rates of Viral Suppression, Alanine Aminotransferase Normalization, and Favorable Bone and Renal Safety in Chinese Chronic Hepatitis B Patients. J Clin Transl Hepatol 2024; 12:469-480. [PMID: 38779514 PMCID: PMC11106352 DOI: 10.14218/jcth.2023.00417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 01/14/2024] [Accepted: 02/02/2024] [Indexed: 05/25/2024] Open
Abstract
BACKGROUND AND AIMS After 3-years (144 week) of double-blind treatment in Chinese chronic hepatitis B patients in two ongoing phase 3 studies, tenofovir alafenamide (TAF) showed similar efficacy to tenofovir disoproxil fumarate (TDF), with improved renal and bone safety. In this study, we aimed to report the 5-year results from 2 years into the open-label TAF treatment phase. METHODS All participants completing the 144-week double-blind treatment were eligible to receive open-label TAF 25 mg once daily up to week 384. Serial analysis of viral suppression (hepatitis B virus DNA <29 IU/mL), alanine aminotransferase normalization, serological responses, and safety outcomes at year 5 (week 240) was performed. RESULTS The open-label phase included 93% (311/334) of the enrolled participants, which included 212 who switched from double-blind TAF to open-label TAF (TAF-TAF) and 99 who switched from double-blind TDF to open-label TAF (TDF-TAF). Baseline characteristics were comparable. Week 240 viral suppression rates were similar between groups [93.4% vs. 93.9%; difference: -1.5%, (95% CI: -6.4 to -3.5), p=0.857]. Alanine aminotransferase normalization and serological response rates were higher in the TAF-TAF group than in the TDF-TAF group. The frequencies of adverse events and laboratory abnormalities were low and similar between groups. Both groups had similar small numerical declines from baseline in estimated glomerular filtration rate at year 5 (week 240, -2.85 mL/min vs. -3.29 mL/min, p=0.910). The greater declines in renal and bone parameters in the TDF-TAF group through week 144 improved after switching to TAF. CONCLUSIONS The 5-year TAF treatment efficacy was high and similar to that of 3-year TDF followed by 2-year TAF in Chinese chronic hepatitis B patients. Favorable effects on bone and renal parameters were sustained with TAF treatment alone and were observed following the switch from TDF to TAF.
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Affiliation(s)
- Jinlin Hou
- Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Qin Ning
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zhongping Duan
- Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Yu Chen
- Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Qing Xie
- Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lunli Zhang
- The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Shanming Wu
- Shanghai Public Health Clinical Center, Shanghai, China
| | - Hong Tang
- West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jun Li
- The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Feng Lin
- Hainan General Hospital, Haikou, Hainan, China
| | - Yongfeng Yang
- The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Guozhong Gong
- The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | | | | | | | | | | | | | | | | | - Chengwei Chen
- The People’s Liberation Army No. 85 Hospital, Shanghai, China
| | - Yan Huang
- Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Mingxiang Zhang
- The Sixth People’s Hospital of Shenyang, Shenyang, Liaoning, China
| | - Jidong Jia
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
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13
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Cai X, Peng S, Xiao X, Huang Z, Zhang P. Serum ApoB/ApoA1 ratio in patients with CHB and the occurrence of HBV related cirrhosis and HBV related hepatocellular carcinoma. Sci Rep 2024; 14:10996. [PMID: 38744926 PMCID: PMC11094140 DOI: 10.1038/s41598-024-61820-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2024] [Accepted: 05/09/2024] [Indexed: 05/16/2024] Open
Abstract
Clinical research has suggested that chronic HBV infection exerts a certain effect on the occurrence of cardiovascular disease by regulating cholesterol metabolism in liver cells. High serum apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) ratio plays a certain role in the above regulation, and it serves as a risk factor for cardiovascular disease. However, whether the ApoB/ApoA1 ratio is correlated with chronic HBV infection and its disease progression remains unclear. In accordance with the inclusion and exclusion criteria, all 378 participants administrated at Renmin Hospital of Wuhan University from March 2021 to March 2022, fell into Healthy Control (HC) group (50 participants), Hepatocellular carcinoma (HCC) group (107 patients), liver cirrhosis (LC) group (64 patients), chronic hepatitis B (CHB) group (62 patients), chronic hepatitis C (CHC) group (46 patients) and Hepatitis E Virus (HEV) group (49 patients). Serum ApoA1 and ApoB concentrations were measured at admission, and the ApoB/ApoA1 ratio was determined. The levels of laboratory parameters in the respective group were compared and ApoB/ApoA1 ratios in HCC patients and LC patients with different severity were further analyzed. ROC curves were plotted to analyze the early diagnostic ability of ApoB/ApoA1 ratio for HBV-associated HCC. Logistic regression and restricted cubic spline analysis were used to explore the correlation between ApoB/ApoA1 ratio and LC and HCC risk. A comparison was drawn in terms of ApoB/ApoA1 ratio between the groups, and the result was expressed in descending sequence: HEV group > CHB group > LC group > HCC group > CHC group > HC group, early-stage HCC < middle-stage HCC < advanced-stage HCC, Class A LC < Class B LC < Class C LC. Serum ApoB/ApoA1 ratio combined diagnosis with AFP exhibited the capability of increasing the detection efficacy and specificity of AFP for HCC and AFP-negative HCC. The incidence of LC and HCC in the respective logistic regression model showed a negative correlation with the serum ApoB/ApoA1 ratio in CHB patients (P < 0.05). After all confounding factors covered in this study were regulated, the result of the restricted cubic spline analysis suggested that in a certain range, serum ApoB/ApoA1 ratio showed an inverse correlation with the prevalence of LC or HCC in CHB patients. Serum ApoB/ApoA1 ratio in CHB patients may be conducive to identifying high-risk patients for HCC or LC, such that LC and HCC can be early diagnosed and treated.
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Affiliation(s)
- Xin Cai
- Department of Clinical Laboratory, Institute of Translational Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, People's Republic of China
| | - Shi Peng
- Department of Clinical Laboratory, Institute of Translational Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, People's Republic of China
| | - Xuan Xiao
- Department of Clinical Laboratory, Institute of Translational Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, People's Republic of China
| | - Zhaoyang Huang
- Department of Clinical Laboratory, Institute of Translational Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, People's Republic of China
| | - Pingan Zhang
- Department of Clinical Laboratory, Institute of Translational Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, People's Republic of China.
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14
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Gao Y, Wang M, Liu X. Noninvasive serum markers for predicting significant liver histopathology in HBeAg-negative chronic HBV-infected patients with normal alanine aminotransferase. Microbiol Spectr 2024; 12:e0394123. [PMID: 38426768 PMCID: PMC11325860 DOI: 10.1128/spectrum.03941-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Accepted: 12/16/2023] [Indexed: 03/02/2024] Open
Abstract
This study is to explore the proportion of significant liver histopathology in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV)-infected patients with normal alanine aminotransferase (ALT) and investigate noninvasive indicators for predicting significant liver histopathology. A total of 201 HBeAg-negative chronic HBV-infected patients with normal ALT who underwent liver biopsy were involved in this study. Significant liver histological changes were defined as necroinflammation grade ≥2 (G ≥ 2) and/or fibrosis stage ≥2 (S ≥ 2). The results showed that 42.3% (85/201) and 45.8% (92/201) of the HBeAg-negative patients with normal ALT have significant liver necroinflammation (G ≥ 2) and fibrosis (S ≥ 2), respectively. High normal ALT (>22 U/L), high level of serum HBV DNA (>3.42 log IU/mL), and low level of prealbumin (PA) (<170 mg/L) were independent predictors for significant liver necroinflammation, and the predictive value of the combined indicators was 0.750 (P < 0.001), while high normal ALT (>24 U/L) and high level of FIB-4 (>1.53) were independent predictors for significant liver fibrosis, and the predictive value of the combined indicators was 0.740 (P < 0.001). In conclusion, more than 40% of HBeAg-negative patients with normal ALT have significant liver histopathology and require immediate antiviral treatment. ALT, PA, HBV DNA, and FIB-4 can independently predict significant liver inflammation and fibrosis for HBeAg-negative patients with normal ALT. Lowering the treatment threshold of ALT may benefit the HBeAg-negative chronic HBV-infected patients. IMPORTANCE Hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV)-infected patients with normal alanine aminotransferase (ALT) were supposed to have a low risk of progression to cirrhosis or hepatocellular carcinoma, and it was recommended to regularly follow up or undergo liver biopsy to assess liver histopathology according to the major international guidelines. However, this study indicates that a considerable number of HBeAg-negative chronic HBV-infected patients with normal ALT have significant liver histopathology and require immediate antiviral treatment. Besides, several clinical commonly used noninvasive indicators were found that can be used to predict significant liver histopathology; thereby liver biopsy might be avoided for HBeAg-negative chronic HBV-infected patients with normal ALT.
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Affiliation(s)
- Yuhua Gao
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Key Clinical Laboratory of Henan Province, Zhengzhou, Henan, China
| | - Mingyang Wang
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Key Clinical Laboratory of Henan Province, Zhengzhou, Henan, China
| | - Xia'nan Liu
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Key Clinical Laboratory of Henan Province, Zhengzhou, Henan, China
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15
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Hu YC, Ding XC, Liu HJ, Ma WL, Feng XY, Ma LN. Effects of Lactobacillus paracasei N1115 on gut microbial imbalance and liver function in patients with hepatitis B-related cirrhosis. World J Gastroenterol 2024; 30:1556-1571. [PMID: 38617455 PMCID: PMC11008409 DOI: 10.3748/wjg.v30.i11.1556] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Revised: 01/08/2024] [Accepted: 03/04/2024] [Indexed: 03/21/2024] Open
Abstract
BACKGROUND Hepatitis B cirrhosis (HBC) is a chronic disease characterized by irreversible diffuse liver damage and aggravated by intestinal microbial imbalance and metabolic dysfunction. Although the relationship between certain single probiotics and HBC has been explored, the impact of the complex ready-to-eat Lactobacillus paracasei N1115 (LP N1115) supplement on patients with HBC has not been determined. AIM To compare the changes in the microbiota, inflammatory factor levels, and liver function before and after probiotic treatment in HBC patients. METHODS This study included 160 HBC patients diagnosed at the General Hospital of Ningxia Medical University between October 2018 and December 2020. Patients were randomly divided into an intervention group that received LP N1115 supplementation and routine treatment and a control group that received routine treatment only. Fecal samples were collected at the onset and conclusion of the 12-wk intervention period. The structure of the intestinal microbiota and the levels of serological indicators, such as liver function and inflammatory factors, were assessed. RESULTS Following LP N1115 intervention, the intestinal microbial diversity significantly increased in the intervention group (P < 0.05), and the structure of the intestinal microbiota was characterized by an increase in the proportions of probiotic microbes and a reduction in harmful bacteria. Additionally, the intervention group demonstrated notable improvements in liver function indices and significantly lower levels of inflammatory factors (P < 0.05). CONCLUSION LP N1115 is a promising treatment for ameliorating intestinal microbial imbalance in HBC patients by modulating the structure of the intestinal microbiota, improving liver function, and reducing inflammatory factor levels.
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Affiliation(s)
- Yan-Chao Hu
- Department of Infectious Disease, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Xiang-Chun Ding
- Department of Infectious Disease, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
- Infectious Disease Clinical Research Center of Ningxia, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Hui-Juan Liu
- Department of Infectious Disease, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Wan-Long Ma
- Department of Infectious Disease, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Xue-Yan Feng
- Department of Infectious Disease, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Li-Na Ma
- Department of Infectious Disease, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
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Huang J, Su M, Kong F, Chen H, Wu S, Guo J, Wu H. Genetic variants in the 6p21.3 region influence hepatitis B virus clearance and chronic hepatitis B risk in the Han Chinese population. LIVER RESEARCH 2024; 8:54-60. [PMID: 39959030 PMCID: PMC11771252 DOI: 10.1016/j.livres.2024.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 10/16/2023] [Accepted: 02/23/2024] [Indexed: 02/18/2025]
Abstract
Background and aim A genome-wide association study has indicated the association of numerous genes in the 6p21.3 region with chronic hepatitis B virus (HBV) infection. In this study, we screened 12 representative single-nucleotide polymorphisms (SNPs) from the 6p21.3 region and investigated their association with the risk of chronic hepatitis B (CHB) to better understand the molecular etiology underlying CHB risk in the Han Chinese population. Methods Between March 2021 and November 2022, we included 183 patients with CHB (case group) and 196 with natural HBV clearance (control group). Allele typing of the selected SNPs was performed using snapshot technology. The correlation between the 12 chosen SNPs and the risk of chronic HBV infection was examined using binary logistic regression analysis. Interacting genes of the variants were identified, and expression quantitative trait loci (eQTL) were analyzed using the 3DSNP database. Results We validated 12 previously reported CHB susceptibility sites, including rs1419881 of transcription factor 19 (TCF19), rs3130542 and rs2853953 of human leukocyte antigen (HLA)-C, rs652888 of euchromatic histone-lysine-methyltransferase 2 (EHMT2), rs2856718, rs9276370, rs7756516, and rs7453920 of HLA-DQ, rs378352 of HLA-DOA, and rs3077, rs9277535, and rs9366816 of HLA-DP. Logistic regression analyses revealed that polymorphisms such as rs9276370, rs7756516, rs7453920, rs3077, rs9277535, and rs9366816 were positively correlated with natural HBV clearance in the dominant model. Conversely, rs3130542 and rs378352 were identified as risk factors for CHB. Haplotype analysis revealed that rs9276370, rs7756516, and rs7453920 in HLA-DQ were TTG and GCA haplotypes. Although the TTG haplotype was positively correlated with a higher risk of CHB, the GCA haplotype significantly influenced the natural clearance of HBV. Bioinformatics analysis demonstrated that rs378352, rs3077, and rs9366816 were located within enhancer states; rs3077 and rs9366816 overlapped with nine transcription factor-binding sites, whereas rs378352 altered five sequence motifs. Furthermore, eQTL analysis demonstrated the functional tendencies of eight statistically significant SNPs (rs3130542, rs9276370, rs7756516, rs7453920, rs378352, rs3077, rs9277535, and rs9366816). Conclusions Genetic variations within the 6p21.3 region were associated with chronic HBV infection in the Han Chinese population in southern China. Furthermore, the GCA haplotype including rs9276370, rs7756516, and rs7453920 of HLA-DQ contributed significantly to natural HBV clearance, implying that multiple SNPs exert a cumulative allelic effect on HBV infection.
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Affiliation(s)
- Jiancheng Huang
- Department of Laboratory Medicine, Mindong Hospital Affiliated to Fujian Medical University, Fuan, Fujian, China
| | - Mingkuan Su
- Department of Laboratory Medicine, Mindong Hospital Affiliated to Fujian Medical University, Fuan, Fujian, China
| | - Fanhui Kong
- Department of Laboratory Medicine, Mindong Hospital Affiliated to Fujian Medical University, Fuan, Fujian, China
| | - Hongbin Chen
- Department of Laboratory Medicine, Mindong Hospital Affiliated to Fujian Medical University, Fuan, Fujian, China
| | - Shuiqing Wu
- Department of Gastroenterology, Mindong Hospital Affiliated to Fujian Medical University, Fuan, Fujian, China
| | - Jianfeng Guo
- Department of Laboratory Medicine, Mindong Hospital Affiliated to Fujian Medical University, Fuan, Fujian, China
| | - Haiying Wu
- Department of Laboratory Medicine, Mindong Hospital Affiliated to Fujian Medical University, Fuan, Fujian, China
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Qiu S, Jin L, Yang D, Zhang D. MTHFR and MTRR gene polymorphisms in patients with chronic hepatitis B virus infections in Zigong, Sichuan Province. Ann Hum Biol 2024; 51:2330926. [PMID: 38634541 DOI: 10.1080/03014460.2024.2330926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Accepted: 02/29/2024] [Indexed: 04/19/2024]
Abstract
BACKGROUND Chronic hepatitis B virus (HBV) infection is a severe disease affecting the physical and economic well-being of patients. The relationship between polymorphisms in the MTHFR gene and disease progression following HBV infection remains a controversial topic. AIM To study MTHFR and MTRR gene polymorphisms in patients with chronic HBV infections in Zigong, Sichuan Province. SUBJECTS AND METHODS One hundred and ninety-one patients with chronic HBV infections were divided into three groups: the chronic hepatitis B (CHB) group (n = 71), the hepatitis B-induced liver cirrhosis (LC) group (n = 56), and the hepatitis B-related primary liver cancer (PLC) group (n = 64). The gene polymorphisms were detected using the PCR-melt curve method and analysed. RESULTS The distributions of MTHFR C677T (CC: 41.2% vs. 41.8%; CT: 50% vs. 45.5%; TT: 8.8% vs. 12.7%; p = 0.714), MTHFR A1298C (AA: 70.6% vs. 72.7%; AC: 26.5% vs. 25.5%; CC: 2.9% vs. 1.8%; p = 1.000), and MTRR A66G (AA: 58.1% vs. 65.5%; AG: 39.0% vs. 29.1%; 2.9% vs. 5.5%; p = 0.353) genetic polymorphisms did not vary between male and female patients from Zigong. In addition, there were no differences in the distributions of MTHFR C677T (CC: 43.4% vs. 38.8%; CT: 49.1% vs. 48.2%; TT: 7.5% vs. 12.9%; p = 0.444), MTHFR A1298C (AA: 76.4% vs. 64.7%; AC: 20.8% vs. 32.9%; CC: 2.8% vs. 2.4%; p = 0.155), and MTRR A66G (AA: 62.3% vs. 57.6%; AG: 34.0% vs. 38.8%; 3.8% vs. 3.5%; p = 0.353) genetic polymorphisms between the patients <60 and >60 years of age. The distributions of MTHFR C677T (CHB vs. LC, p = 0.888; CHB vs. PLC, p = 0.661; PLC vs. LC, p = 0.926), MTHFR A1298C (CHB vs. LC, p = 0.12; CHB vs. PLC, p = 0.263; PLC vs. LC, p = 0.550), and MTRR A66G (CHB vs. LC, p = 0.955; CHB vs. PLC, p = 0.645; PLC vs. LC, p = 0.355) gene polymorphisms were comparable between the CHB, LC, and PLC groups. CONCLUSION The distributions of MTHFR and MRRR genetic polymorphisms in the population with HBV infections in Zigong, Sichuan Province did not differ in age and sex. The MTHFR and MRRR genetic polymorphisms were comparable between the CHB, LC, and PLC groups.
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Affiliation(s)
- Shunhua Qiu
- Department of Clinical Laboratory, Zigong Third People's Hospital, Zigong City, Sichuan Province, P.R. China
| | - Lifen Jin
- Department of Clinical Pharmacy, Zigong Third People's Hospital, Zigong City, Sichuan Province, P.R. China
| | - Dan Yang
- Department of Clinical Laboratory, Zigong Third People's Hospital, Zigong City, Sichuan Province, P.R. China
| | - Dewen Zhang
- Department of Clinical Laboratory, Zigong Third People's Hospital, Zigong City, Sichuan Province, P.R. China
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18
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Hao X, Fan R, Zeng HM, Hou JL. Hepatocellular Carcinoma Risk Scores from Modeling to Real Clinical Practice in Areas Highly Endemic for Hepatitis B Infection. J Clin Transl Hepatol 2023; 11:1508-1519. [PMID: 38161501 PMCID: PMC10752803 DOI: 10.14218/jcth.2023.00087] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 05/04/2023] [Accepted: 06/02/2023] [Indexed: 01/03/2024] Open
Abstract
Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers and represents a global health challenge. Liver cancer ranks third in cancer-related mortality with 830,000 deaths and sixth in incidence with 906,000 new cases annually worldwide. HCC most commonly occurs in patients with underlying liver disease, especially chronic hepatitis B virus (HBV) infection in highly endemic areas. Predicting HCC risk based on scoring models for patients with chronic liver disease is a simple, effective strategy for identifying and stratifying patients to improve the early diagnosis rate and prognosis of HCC. We examined 23 HCC risk scores published worldwide in CHB patients with (n=10) or without (n=13) antiviral treatment. We also described the characteristics of the risk score's predictive performance and application status. In the future, higher predictive accuracy could be achieved by combining novel technologies and machine learning algorithms to develop and update HCC risk score models and integrated early warning and diagnosis systems for HCC in hospitals and communities.
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Affiliation(s)
- Xin Hao
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangdong Provincial Institute of Liver Diseases, Guangzhou, Guangdong, China
| | - Rong Fan
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangdong Provincial Institute of Liver Diseases, Guangzhou, Guangdong, China
| | - Hong-Mei Zeng
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jin-Lin Hou
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangdong Provincial Institute of Liver Diseases, Guangzhou, Guangdong, China
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19
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Zhou J, Wang FD, Li LQ, Li YJ, Wang SY, Chen EQ. Antiviral Therapy Favors a Lower Risk of Liver Cirrhosis in HBeAg-negative Chronic Hepatitis B with Normal Alanine Transaminase and HBV DNA Positivity. J Clin Transl Hepatol 2023; 11:1465-1475. [PMID: 38161505 PMCID: PMC10752813 DOI: 10.14218/jcth.2023.00272] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 07/01/2023] [Accepted: 07/26/2023] [Indexed: 01/03/2024] Open
Abstract
BACKGROUND AND AIMS Direct evidence on the outcomes of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients with normal alanine transaminase after long-term antiviral treatment is lacking. METHODS HBeAg-negative patients with normal ALT and positive HBV DNA (≥20 IU/mL) were retrospectively enrolled. The endpoints included virological response (HBV DNA<100 IU/mL), changes in aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 index (FIB-4), and the incidence of liver nodules, cirrhosis, and hepatocellular carcinoma (HCC). RESULTS This cohort (n=194) was divided into three subgroups, untreated (n=67), treatment-continued (n=87), and treatment-discontinued patients (n=40), with a median follow-up of 54 months. The treatment-continued group achieved 100% (95% CI: 94.7-100) virological response, and significantly reduced APRI and FIB-4 scores (both p<0.001). The risk of liver nodules and cirrhosis in that group was reduced by 76% (HR: 0.24, 95% CI: 0.11-0.54, p<0.001) and 89% (HR: 0.11, 95% CI: 0.14-0.91, p=0.041) vs. the untreated group and by 77% (HR: 0.23, 95% CI: 0.10-0.49, p<0.001) and 95% (HR: 0.05, 95% CI: 0.01-0.44, p=0.006) vs. the treatment-discontinued group. For patients with HBV DNA≥2,000 IU/mL, adherence to treatment lowered the risks of liver cirrhosis by 92% (95% CI: 0.01-0.67) and 93% (95% CI: 0.01-0.53) vs. the untreated and treatment-discontinued patients, respectively. No patient adhering to treatment developed HCC, but one in each of the remaining groups did. CONCLUSIONS Continuous nucleos(t)ide analog (NA) treatment has a satisfactory effectiveness and helps to lower the risk of liver cirrhosis in HBeAg-negative CHB patients with normal alanine transaminase, especially in those with HBV DNA≥2,000 IU/mL.
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Affiliation(s)
- Jing Zhou
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Fa-Da Wang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Lan-Qing Li
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yu-Jin Li
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Shi-Yan Wang
- Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - En-Qiang Chen
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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20
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Zhang L, Yang L, Gao Y, Bi X, Lin Y, Deng W, Jiang T, Lu Y, Hao H, Wan G, Yi W, Xie Y, Li M. Nomogram for evaluating obvious liver inflammation in treatment-naïve HBeAg positive chronic hepatitis B virus infection patients with normal ALT. Virulence 2023; 14:2158710. [PMID: 36600180 PMCID: PMC9828634 DOI: 10.1080/21505594.2022.2158710] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Accepted: 12/11/2022] [Indexed: 01/06/2023] Open
Abstract
The purpose of this study was to develop an effective and non-invasive nomogram for evaluating liver obvious inflammation in untreated HBeAg positive patients with chronic hepatitis B virus (HBV) infection. A nomogram was established on a model cohort of 292 treatment-naïve HBeAg positive patients with normal alanine aminotransferase (ALT ≤40 U/L) at Beijing Ditan Hospital from January 2008 to March 2018. Then the nomogram was prospectively validated in a cohort of 88 patients from July 2019 to May 2021. Calibration curves and Concordance index were used to evaluate the accuracy of prediction and identification performance of the model. In untreated HBeAg positive chronic hepatitis B virus infection patients with normal ALT, the formula for predicting liver inflammation was Logit (P) =-0.91-0.41×log10 (qHBeAg)+0.11×AST-0.01×PLT. The nomogram had C-index of 0.751 (95% CI, 0.688-0.815), indicating a good consistency between prediction and real observation on the model cohort. The validation cohort confirmed its good performance. In this study, liver inflammation nomograms based on HBeAg, AST, and PLT were established and verified in treatment-naïve HBeAg positive chronic HBV patients with normal ALT.
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Affiliation(s)
- Lu Zhang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Liu Yang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yuanjiao Gao
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xiaoyue Bi
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yanjie Lin
- Department of Medical Record Statistics, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Wen Deng
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Tingting Jiang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yao Lu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Hongxiao Hao
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Gang Wan
- Department of Gynecology and Obstetrics, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Wei Yi
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
| | - Yao Xie
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Department of Medical Record Statistics, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Minghui Li
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Department of Medical Record Statistics, Beijing Ditan Hospital, Capital Medical University, Beijing, China
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21
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Zhan J, Wang J, Zhang Z, Xue R, Jiang S, Liu J, Liu Y, Zhu L, Xia J, Yan X, Ding W, Zhu C, Qiu Y, Li J, Huang R, Wu C. Noninvasive diagnosis of significant liver inflammation in patients with chronic hepatitis B in the indeterminate phase. Virulence 2023; 14:2268497. [PMID: 37938933 PMCID: PMC10653690 DOI: 10.1080/21505594.2023.2268497] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2023] [Accepted: 10/04/2023] [Indexed: 11/10/2023] Open
Abstract
The presence of significant liver inflammation is an important indication for antiviral treatment in patients with chronic hepatitis B (CHB) in the indeterminate phase. We aimed to establish a non-invasive nomogram to predict significant liver inflammation in these patients. A total of 195 CHB patients in the indeterminate phase were randomly split into training and validation sets. The least absolute shrinkage and selection operator and logistic regression were applied to identify risk factors and establish a predictive model. A calibration curve, decision curve analysis (DCA), and receiver operating characteristic (ROC) curve were applied to assess the performance of the nomogram. The median age was 42.0 y and 59.5% of the patients were male. Alkaline phosphatase, γ-glutamyl transpeptidase, and prothrombin time were independent predictors for significant liver inflammation and selected to establish the AGP-nomogram. The calibration plot demonstrated that the predicted results matched the actual values. The DCA showed a high net benefit when the threshold probability was 25-83% in the training set and 31-100% in the validation set. The areas under ROC curves of AGP-nomogram in predicting significant inflammation were significantly higher than ALT in the training set (0.744 vs. 0.642, P = 0.049) and validation set (0.766 vs. 0.660, P = 0.047). The ability of AGP-nomogram in predicting advanced inflammation was also superior to ALT. The AGP-nomogram can accurately identify significant inflammation in CHB patients in the indeterminate phase, and its application may reduce the need for liver biopsy and help identify candidates for antiviral treatment.Abbreviations: AASLD: American Association for the Study of Liver Diseases; ALB: albumin; ALP: alkaline phosphatase; ALT: alanine aminotransferase; APRI: aspartate aminotransferase-to-platelet ratio index; AST: aspartate aminotransferase; AUROC: area under the receiver operating characteristic curve; CHB: chronic hepatitis B; CI: confidence interval; DCA: decision curve analysis; FIB-4: fibrosis index based on the four factors; GLB: globulin; GGT: γ-glutamyl transpeptidase; HBcAb: hepatitis B core antibody; HBeAg: hepatitis B e antigen; HBsAg: hepatitis B surface antigen; HBV: hepatitis B virus; HCC: hepatocellular carcinoma; HIV: human immunodeficiency virus; INR: international-normalized ratio; IQR: interquartile range; LASSO: least absolute shrinkage and selection operator; LB: liver biopsy; LR: Likelihood ratio; NAFLD: non-alcoholic fatty liver disease; NPV: negative predictive value; PLT: platelets; PPV: positive predictive value; PT: prothrombin time; ROC: receiver operating characteristic; TB: total bilirubin; TE: transient elastography; ULN: upper limit of normal.
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Affiliation(s)
- Jie Zhan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
- Department of General Practice, Jiangpu Street Community Health Service Center, Nanjing, Jiangsu, China
| | - Jian Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Zhiyi Zhang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Ruifei Xue
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Suling Jiang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Jiacheng Liu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Yilin Liu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Li Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Juan Xia
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Xiaomin Yan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Weimao Ding
- Department of Hepatology, Huai’an No. 4 People’s Hospital, Huai’an, Jiangsu, China
| | - Chuanwu Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Yuanwang Qiu
- Department of Infectious Diseases, The Fifth People’s Hospital of Wuxi, Wuxi, Jiangsu, China
| | - Jie Li
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Rui Huang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Chao Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
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22
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You H, Wang F, Li T, Xu X, Sun Y, Nan Y, Wang G, Hou J, Duan Z, Wei L, Jia J, Zhuang H. Guidelines for the Prevention and Treatment of Chronic Hepatitis B (version 2022). J Clin Transl Hepatol 2023; 11:1425-1442. [PMID: 37719965 PMCID: PMC10500285 DOI: 10.14218/jcth.2023.00320] [Citation(s) in RCA: 77] [Impact Index Per Article: 38.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 08/02/2023] [Accepted: 08/03/2023] [Indexed: 09/19/2023] Open
Abstract
To facilitate the achieving of the goal of "eliminating viral hepatitis as a major public health threat by 2030" set by the World Health Organization, the Chinese Society of Hepatology together with the Chinese Society of Infectious Diseases (both are branches of the Chinese Medical Association) organized a panel of experts and updated the guidelines for prevention and treatment of chronic hepatitis B in China (version 2022). With the support of available evidence, this revision of the guidelines focuses on active prevention, large scale testing, and expansion of therapeutic indication of chronic hepatitis B with the aim of reducing the hepatitis B related disease burden.
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Affiliation(s)
- Hong You
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Fusheng Wang
- The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Taisheng Li
- Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Xiaoyuan Xu
- Peking University First Hospital, Beijing, China
| | - Yameng Sun
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yuemin Nan
- Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | | | - Jinlin Hou
- Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Zhongping Duan
- Beijing You-An Hospital, Capital Medical University, Beijing, China
| | - Lai Wei
- Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Jidong Jia
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Hui Zhuang
- Peking University Health Science Center, Beijing, China
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23
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Li YP, Liu CR, Hao M, Lu R, Dang SS. Clinical cure of hepatitis B: Delight and anticipation. Shijie Huaren Xiaohua Zazhi 2023; 31:837-845. [DOI: 10.11569/wcjd.v31.i20.837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 10/05/2023] [Accepted: 10/23/2023] [Indexed: 10/27/2023] Open
Affiliation(s)
- Ya-Ping Li
- Department of Infectious Diseases, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
| | - Chen-Rui Liu
- Department of Infectious Diseases, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
| | - Miao Hao
- Department of Infectious Diseases, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
| | - Rui Lu
- Department of Infectious Diseases, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
| | - Shuang-Suo Dang
- Department of Infectious Diseases, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
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Cao L, Li S, Dong J, Wen J, Ding L, Ge Y, Yang Q, Xu X, Zhuang H. Safety of entecavir antiviral therapyduring an accidental pregnancy in patients with chronic hepatitis B. Biomed Rep 2023; 19:72. [PMID: 37746589 PMCID: PMC10511944 DOI: 10.3892/br.2023.1654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Accepted: 08/18/2023] [Indexed: 09/26/2023] Open
Abstract
The present study aimed to investigate the effects of accidental pregnancy CHB patients' reproductive age on their offspring during entecavir (ETV) antiviral therapy. A total of 112 couples were retrospectively enrolled, and they were divided into an observational and control group. A total of 53 couples who had accidental pregnancies while receiving long-term ETV antiviral medication were recruited for the observational group. The control group consisted of 59 couples who became pregnant accidentally while receiving long-term tenofovir disoproxil fumarate (TDF) antiviral treatment. All mothers persisted in their pregnancies in the observational group, and ETV was promptly replaced with TDF. Every mother remained pregnant and continued to use TDF in the control group. The maternal and baby safety profiles, including the prevalence of congenital disabilities, were comparable across the observational and control groups at delivery. In addition, no unusual indications or symptoms of the newborns were noted during the follow-up intervals of 28, 48, and 96 weeks postpartum. Initiating ETV or TDF in early and middle pregnancy seems safe for mothers and infants. Important data from the present study support using ETV in early-mid gestational accidental pregnancies and the prompt substitution of TDF antiviral medication for ETV.
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Affiliation(s)
- Lihua Cao
- Liver Disease Center, Qinhuangdao Third Hospital, Qinhuangdao, Hebei 066000, P.R. China
| | - Shiwu Li
- Liver Disease Center, Qinhuangdao Third Hospital, Qinhuangdao, Hebei 066000, P.R. China
| | - Jingchao Dong
- Liver Disease Center, Qinhuangdao Third Hospital, Qinhuangdao, Hebei 066000, P.R. China
| | - Jingkui Wen
- Liver Disease Center, Qinhuangdao Third Hospital, Qinhuangdao, Hebei 066000, P.R. China
| | - Lina Ding
- Liver Disease Center, Qinhuangdao Third Hospital, Qinhuangdao, Hebei 066000, P.R. China
| | - Yahui Ge
- Liver Disease Center, Qinhuangdao Third Hospital, Qinhuangdao, Hebei 066000, P.R. China
| | - Qing Yang
- Department of Obstetrics, Qinhuangdao Women's and Children's Hospital, Qinhuangdao, Hebei 066000, P.R. China
| | - Xiaoyuan Xu
- Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, P.R. China
| | - Hui Zhuang
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, P.R. China
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25
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Ye J, Lin Y, Shao C, Sun Y, Feng S, Zhong B. Comparisons of Insulin Resistance- and Steatosis-Based Scores in Monitoring Metabolic Associated Fatty Liver Disease Treatment Response. ANNALS OF NUTRITION & METABOLISM 2023; 79:448-459. [PMID: 37678173 DOI: 10.1159/000530531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Accepted: 10/28/2022] [Indexed: 09/09/2023]
Abstract
BACKGROUND Quantitative measurements of liver fat contents (LFCs) by magnetic resonance imaging derived-proton density fat fraction (MRI-PDFF) are accurate but limited by availability, convenience, and expense in the surveillance of metabolic associated fatty liver (MAFLD). Insulin resistance (IR) and steatosis-associated serum indices are useful in screening for MAFLD, but their value in monitoring MAFLD with or without chronic hepatitis B virus (CHB) infection remains unclear and we aimed to evaluate these scores in predicting changes in LFC. METHODS We conducted a prospective study between January 2015 and December 2021 with 620 consecutive participants with MAFLD (212 participants with CHB) who received a 24-week lifestyle intervention. The homeostasis model assessment of IR (HOMA-IR), HOMA2 index, glucose-insulin ratio, quantitative insulin sensitivity check index, fasting insulin resistance index, fatty liver index (FLI), hepatic steatosis index (HSI), liver fat score (LFS), visceral adiposity index, and triglycerides * glucose were calculated. RESULTS When using endpoints such as LFS improvements of ≥5% or 10% or escalations of ≥5%, LFS had the highest area under the curve (AUC) values at all endpoints for MAFLD alone (0.756, 95% CI: 0.707-0.805; 0.761, 95% CI: 0.705-0.818; 0.807, 95% CI: 0.713-0.901, all p < 0.05, respectively). With CHB, the FLI (AUC = 0.750) and HIS (AUC = 0.770) exhibited the highest AUCs between the former two outcomes, respectively, but no score could predict LFC escalation of ≥5%. CONCLUSION Among IR and steatosis scores, changes in LFC through lifestyle interventions can be captured with LFS possessing moderate precision but not in those with CHB.
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Affiliation(s)
- Junzhao Ye
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yansong Lin
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Congxian Shao
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yanhong Sun
- Department of Clinical Laboratories, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Shiting Feng
- Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Bihui Zhong
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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Lai RM, Lin S, Wang MM, Li N, Zhou JH, Lin XY, Chen TB, Zhu YY, Zheng Q. Tenofovir alafenamide significantly increased serum lipid levels compared with entecavir therapy in chronic hepatitis B virus patients. World J Hepatol 2023; 15:964-972. [PMID: 37701915 PMCID: PMC10494560 DOI: 10.4254/wjh.v15.i8.964] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 05/26/2023] [Accepted: 08/03/2023] [Indexed: 08/22/2023] Open
Abstract
BACKGROUND Tenofovir alafenamide (TAF) has a serum lipid-raising effect in patients with HIV; however, its effect on serum lipids and nonalcoholic fatty liver disease (NAFLD) risk in patients with chronic hepatitis B (CHB) is unclear. AIM To compare the effects of TAF and entecavir (ETV) on serum lipid levels in patients with CHB. METHODS In this retrospective cohort study, the data including the clinical features, serum lipids, and metabolic factors of patients with CHB at baseline and approximately 1 year after TAF or ETV treatment were collected and analyzed. We used propensity score-matched models to assess the effects on high-density lipoprotein, low-density lipoprotein, triglycerides, and total cholesterol (TCHO). RESULTS A total of 336 patients (75.60% male) were included; 63.69% received TAF and 36.31% received ETV. Compared with the ETV group, the TAF group had significantly higher TCHO levels after treatment (4.67 ± 0.90 vs 4.36 ± 1.05, P = 0.006). In a propensity score-matched model for body mass index, age, sex, smoking, drinking, presence of comorbidities such as NAFLD, cirrhosis, diabetes mellitus, and hypertension, TAF-treated patients had significantly increased TCHO levels compared to that at baseline (P = 0.019). There was no difference for the ETV group. Body mass index, sex, hypertension, baseline TCHO, and creatine kinase-MB isoenzyme levels were significantly associated with elevated TCHO levels in logistic regression analysis. However, 1-year TAF treatment did not increase the incidence of NAFLD. CONCLUSION A greater increase in TCHO was observed in patients with CHB receiving TAF compared to those receiving ETV. However, TAF-induced dyslipidemia did not increase the incidence of NAFLD.
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Affiliation(s)
- Rui-Min Lai
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fujian Clinical Research Center for Hepatopathy and Intestinal Diseases, Fuzhou 350005, Fujian Province, China
- Department of Hepatology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, Fujian Province, China
| | - Shan Lin
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fujian Clinical Research Center for Hepatopathy and Intestinal Diseases, Fuzhou 350005, Fujian Province, China
| | - Miao-Miao Wang
- Department of Endocrinology, The 910th Hospital of The Joint Service Support Force, Quanzhou 362000, Fujian Province, China
| | - Na Li
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fujian Clinical Research Center for Hepatopathy and Intestinal Diseases, Fuzhou 350005, Fujian Province, China
| | - Jia-Hui Zhou
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fujian Clinical Research Center for Hepatopathy and Intestinal Diseases, Fuzhou 350005, Fujian Province, China
| | - Xiao-Yu Lin
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fujian Clinical Research Center for Hepatopathy and Intestinal Diseases, Fuzhou 350005, Fujian Province, China
| | - Tian-Bin Chen
- Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Yue-Yong Zhu
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fujian Clinical Research Center for Hepatopathy and Intestinal Diseases, Fuzhou 350005, Fujian Province, China
| | - Qi Zheng
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fujian Clinical Research Center for Hepatopathy and Intestinal Diseases, Fuzhou 350005, Fujian Province, China
- Department of Hepatology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, Fujian Province, China.
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Yu T, Li W, Yu T. Management of chronic myelogenous leukemia with COVID-19 and hepatitis B. Front Oncol 2023; 13:1217023. [PMID: 37601670 PMCID: PMC10438954 DOI: 10.3389/fonc.2023.1217023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Accepted: 07/13/2023] [Indexed: 08/22/2023] Open
Abstract
The application of immunosuppressive agents and targeted drugs has opened a novel approach for the treatment of hematological tumors, and the application of tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia is one of the landmark breakthroughs that has considerably improved the prognosis of CML patients. However, with the extensive use of TKI, the co-infection of CML patients has become increasingly apparent, especially regarding infectious diseases such as hepatitis B and COVID-19. The underlying mechanism may be related to the inhibition of the immune function by TKI. Poor management, including disease progression due to the infectious disease or TKI dose reduction or discontinuation, may lead to adverse clinical outcomes and can even be life-threatening. Therefore, this review principally provides an overview of the pathogenesis and standardized management principles of CML patients with comorbid COVID-19 or hepatitis B in order to improve clinicians' awareness of the risks so as to more effectively diagnose and treat CML and improve the survival rate and quality of life of patients. In the past two decades, owing to the advent of imatinib, chronic myeloid leukemia (CML) has transformed into a chronic controllable disease, and even treatment-free remission can be anticipated. Earlier studies have indicated that tyrosine kinase inhibitor (TKI) exerts a peculiar inhibitory effect on the body's immune function. Therefore, with the widespread application of TKI, more and more attention has been paid to the comorbidity of infectious diseases in CML patients, especially in patients with progressive disease or non-remission. Despite some studies revealing that the proportion and severity of SARS-CoV-2 infection in CML patients receiving TKI treatment are lower than in patients with other hematological malignancies, CML patients with stable disease are still recommended to be vaccinated against SARS-CoV-2, while TKI may or may not be discontinued. Meanwhile, the management of CML patients during the epidemic of coronavirus disease 2019 (COVID-19) still necessitates further discussion. This article also provides an overview of TKI-related hepatitis B reactivation. If not managed, patients may face adverse consequences such as hepatitis B reactivation-related hepatitis, liver failure, and progression of CML after forced withdrawal of medication. Therefore, this review aimed to comprehensively describe the management of CML patients with comorbid COVID-19, the pathogenesis of hepatitis B reactivation, the indicated population for prophylactic antiviral therapy, the time of antiviral drug discontinuation, and drug selection.
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Affiliation(s)
- Tian Yu
- Department of Hematology, Affiliated Renhe Hospital of China Three Gorges University, Yichang, China
- College of Basic Medical Sciences, China Three Gorges University, Yichang, China
| | - Weiming Li
- Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tao Yu
- Department of Hematology, Affiliated Renhe Hospital of China Three Gorges University, Yichang, China
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Wang X, Liu H, Qi J, Zeng F, Wang L, Yin P, Liu F, Li H, Liu Y, Liu J, Wei L, Liang X, Wang Y, Rao H, Zhou M. Trends of Mortality in End-Stage Liver Disease - China, 2008-2020. China CDC Wkly 2023; 5:657-663. [PMID: 37593126 PMCID: PMC10427498 DOI: 10.46234/ccdcw2023.128] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 06/15/2023] [Indexed: 08/19/2023] Open
Abstract
Introduction Liver cancer and cirrhosis represent the most prevalent forms of end-stage liver diseases (ESLDs). Notably, in China, deaths attributed to ESLDs contribute significantly to the global mortality rate of these disorders. Enhanced comprehension of the mortality profile associated with ESLDs in China could provide crucial insights into intervention prioritization, which could in turn help reduce the overall global burden of these diseases. Methods Data were obtained from China's Disease Surveillance Points system. The presentation includes both crude and age-standardized mortality rates, stratified by sex, residential location, and region. Using Joinpoint Regression, trends in annual mortality rates were estimated from the period of 2008 to 2020 and expressed as the average annual percentage change (AAPC). Results In 2020, the gross mortality rate of ESLD stood at 30.08 cases per 100,000 individuals. A higher age-standardized ESLD mortality rate was observed in males and rural populations in comparison to their female and urban counterparts, respectively. Noticeably, the highest mortality rates associated with liver cancer and cirrhosis were reported in South and Southwest China, respectively. A positive correlation was noticed between age-specific ESLD mortality rates and advancing age. Interestingly, an annual decrease in the ESLD mortality rate was observed from 2008 to 2020. In urban contexts, the AAPC of cirrhosis was noted to be higher than that of liver cancer. Conclusions The mortality rate associated with ESLDs in China decreased between 2008 and 2020. Nevertheless, the death burden attributable to ESLD continues to be alarmingly high. Future initiatives should prioritize the reduction of ESLD mortality in particular populations: males, elderly individuals, and those residing in rural regions of South and Southwest China. The emphasis of future interventions should be placed on antiviral therapy for adults diagnosed with viral hepatitis, and on the prevention of hepatitis B virus (HBV) infection across all demographics.
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Affiliation(s)
- Xiaoxiao Wang
- Peking University People’s Hospital, Peking University Hepatology Institute, Beijing, China
- Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing, China
| | - Huixin Liu
- Peking University People’s Hospital, Department of Clinical Epidemiology and Biostatistics, Beijing, China
| | - Jinlei Qi
- National Center for Chronic and Non-communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Fangfang Zeng
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou City, Guangdong Province, China
- Disease Control and Prevention Institute of Jinan University, Guangzhou City, Guangdong Province, China
- Jinan University-BioKangtai Vaccine Institute, Jinan University, Guangzhou City, Guangdong Province, China
| | - Lijun Wang
- National Center for Chronic and Non-communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Peng Yin
- National Center for Chronic and Non-communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Feng Liu
- Peking University People’s Hospital, Peking University Hepatology Institute, Beijing, China
- Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing, China
| | - Hongbo Li
- China Center for Economic Research, National School of Development, Peking University, Beijing, China
| | - Yunning Liu
- National Center for Chronic and Non-communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Jiangmei Liu
- National Center for Chronic and Non-communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Lai Wei
- Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Xiaofeng Liang
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou City, Guangdong Province, China
- Disease Control and Prevention Institute of Jinan University, Guangzhou City, Guangdong Province, China
- Jinan University-BioKangtai Vaccine Institute, Jinan University, Guangzhou City, Guangdong Province, China
| | - Yu Wang
- Chinese Foundation for Hepatitis Prevention and Control, Beijing, China
| | - Huiying Rao
- Peking University People’s Hospital, Peking University Hepatology Institute, Beijing, China
- Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing, China
| | - Maigeng Zhou
- National Center for Chronic and Non-communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
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Tian L, Tang S, Wang N, Deng H, Zhang Q, Shi T. Hepatic and portal vein Doppler ultrasounds in assessing liver inflammation and fibrosis in chronic HBV infection with a normal ALT level. Front Med (Lausanne) 2023; 10:1178944. [PMID: 37305137 PMCID: PMC10248231 DOI: 10.3389/fmed.2023.1178944] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 05/08/2023] [Indexed: 06/13/2023] Open
Abstract
Aims To discuss the clinical value of hepatic and portal vein Doppler ultrasounds in assessing liver inflammation and fibrosis in patients with chronic hepatitis B virus (HBV) infection, and a normal alanine transaminase (ALT) level. Methods 94 patients with chronic HBV infections who had undergone ultrasound-guided liver biopsies were enrolled and grouped by the liver tissue pathological results. Analyzed the differences and correlation between parameters of the hepatic and portal vein Doppler ultrasounds are discussed across different degrees of liver inflammation and fibrosis. Results There were 27 patients with no significant liver damage and 67 patients with significant liver damage, there were significant differences in the parameters of the hepatic and portal vein Doppler ultrasounds between them (p < 0.05). As liver inflammation was aggravated, the inner diameter of the portal vein increased, and the blood flow velocities of the portal and superior mesenteric veins decreased (p < 0.05). When liver fibrosis became more severe, the inner diameter of the portal vein increased, while the blood flow velocities of the portal, superior mesenteric, and splenic veins decreased, and the Doppler waveforms of hepatic veins became unidirectional or flat (p < 0.05). The receiver operating characteristic (ROC) curve showed the assessment efficacy of hepatic and portal vein Doppler ultrasounds was superior to abdominal Doppler ultrasound alone in assessing liver fibrosis, and the combination of the two examination techniques outperformed any technique used alone. Conclusion The hepatic and portal vein Doppler ultrasounds have important clinical value for assessing liver fibrosis in patients with chronic HBV infection, to aid improve the diagnosis of liver fibrosis.
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Affiliation(s)
- Li Tian
- Department of Infectious Disease, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Shuyao Tang
- Department of Infectious Disease, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Na Wang
- Department of Infectious Disease, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Huan Deng
- Department of Infectious Disease, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Qunxia Zhang
- Department of Ultrasound Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Tongdong Shi
- Department of Infectious Disease, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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30
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Jiang SW, Lian X, Hu AR, Lu JL, He ZY, Shi XJ, Zhu DD, Wang ZY, Huang GC. Liver histopathological lesions is severe in patients with normal alanine transaminase and low to moderate hepatitis B virus DNA replication. World J Gastroenterol 2023; 29:2479-2494. [PMID: 37179582 PMCID: PMC10167902 DOI: 10.3748/wjg.v29.i16.2479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 03/05/2023] [Accepted: 04/07/2023] [Indexed: 04/24/2023] Open
Abstract
BACKGROUND Chronic hepatitis B virus (HBV) infection remains a major global public health problem. Chronic hepatitis B (CHB) patients can be divided into treatment indication and non-treatment indication individuals according to alanine transaminase (ALT), HBV DNA, serum hepatitis B e antigen status, disease status [liver cirrhosis, hepatocellular carcinoma (HCC), or liver failure], liver necroinflammation or fibrosis, patients' age, and family history of HCC or cirrhosis. For example, normal ALT patients in 'immune-tolerant' phase with HBV DNA higher than 107 or 2 × 107 IU/mL, and those in 'inactive-carrier' phase with HBV DNA lower than 2 × 103 IU/mL do not require antiviral therapy. However, is it reasonable to set the defined values of HBV DNA as the fundamental basis to estimate the disease state and to determine whether to start treatment? In fact, we should pay more attention to those who do not match the treatment indications (gray-zone patients both in the indeterminate phase and in the 'inactive-carrier' phase). AIM To analyze the correlation of HBV DNA level and liver histopathological severity, and to explore the significance of HBV DNA for CHB with normal ALT. METHODS From January 2017 to December 2021, a retrospective cross-sectional set of 1299 patients with chronic HBV infection (HBV DNA > 30 IU/mL) who underwent liver biopsy from four hospitals, including 634 with ALT less than 40 U/L. None of the patients had received anti-HBV treatment. The degrees of liver necroinflammatory activity and liver fibrosis were evaluated according to the Metavir system. On the basis of the HBV DNA level, patients were divided into two groups: Low/moderate replication group, HBV DNA ≤ 107 IU/mL [7.00 Log IU/mL, the European Association for the Study of the Liver (EASL) guidelines] or ≤ 2 × 107 IU/mL [7.30 Log IU/mL, the Chinese Medical Association (CMA) guidelines]; high replication group, HBV DNA > 107 IU/mL or > 2 × 107 IU/mL. Relevant factors (demographic characteristics, laboratory parameters and noninvasive models) for liver histopathological severity were analyzed by univariate analysis, logistics analysis and propensity score-matched analysis. RESULTS At entry, there were 21.45%, 24.29%, and 30.28% of the patients had liver histopathological severities with ≥ A2, ≥ F2, and ≥ A2 or/and ≥ F2, respectively. HBV DNA level (negative correlation) and noninvasive model liver fibrosis 5 value (positive correlation) were independent risk factors for liver histopathological severities (liver necroinflammation, liver fibrosis, and treatment indication). The AUROCs of the prediction probabilities (PRE_) of the models mentioned above (< A2 vs ≥ A2, < F2 vs ≥ F2, < A2 and < F2 vs ≥ A2 or/and ≥ F2) were 0.814 (95%CI: 0.770-0.859), 0.824 (95%CI: 0.785-0.863), and 0.799 (95%CI: 0.760-0.838), respectively. HBV DNA level (negative correlation) was still an independent risk factor when diagnostic models were excluded, the P values (< A2 vs ≥ A2, < F2 vs ≥ F2, < A2 and < F2 vs ≥ A2 or/and ≥ F2) were 0.011, 0.000, and 0.000, respectively. For the propensity score-matched pairs, whether based on EASL guidelines or CMA guidelines, the group with significant liver histology damage (≥ A2 or/and ≥ F2) showed much lower HBV DNA level than the group with non- significant liver histology damage (< A2 and < F2). Patients in the moderate replication group (with indeterminate phase) had the most serious liver disease pathologically and hematologically, followed by patients in the low replication group (with 'inactive-carrier' phase) and then the high replication group (with 'immune-tolerant' phase). CONCLUSION HBV DNA level is a negative risk factor for liver disease progression. The phase definition of CHB may be revised by whether the level of HBV DNA exceeds the detection low limit value. Patients who are in the indeterminate phase or 'inactive carriers' should receive antiviral therapy.
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Affiliation(s)
- Su-Wen Jiang
- Ningbo Institute of Liver Diseases, Ningbo No. 2 Hospital, Ningbo 315020, Zhejiang Province, China
| | - Xiang Lian
- Department of Infectious Diseases, Xiangshan Hospital Affiliated to Wenzhou Medical University, Ningbo 315020, Zhejiang Province, China
| | - Ai-Rong Hu
- Ningbo Institute of Liver Diseases, Ningbo No. 2 Hospital, Ningbo 315020, Zhejiang Province, China
| | - Jia-Lin Lu
- Department of Infectious Diseases, The First Hospital of Ninghai County, Ningbo 315000, Zhejiang Province, China
| | - Zhe-Yun He
- Ningbo Institute of Liver Diseases, Ningbo No. 2 Hospital, Ningbo 315020, Zhejiang Province, China
| | - Xiao-Jun Shi
- Ningbo Institute of Liver Diseases, Ningbo No. 2 Hospital, Ningbo 315020, Zhejiang Province, China
| | - De-Dong Zhu
- Ningbo Institute of Liver Diseases, Ningbo No. 2 Hospital, Ningbo 315020, Zhejiang Province, China
| | - Zong-Yi Wang
- Department of Infectious Diseases, The First Hospital of Ninghai County, Ningbo 315000, Zhejiang Province, China
| | - Guan-Cheng Huang
- Department of Infectious Diseases, The Affiliated Yang-Ming Hospital of Ningbo University, Ningbo 315400, Zhejiang Province, China
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Lu H, Cao W, Zhang L, Yang L, Bi X, Lin Y, Deng W, Jiang T, Sun F, Zeng Z, Lu Y, Zhang L, Liu R, Gao Y, Wu S, Hao H, Chen X, Hu L, Xu M, Xiong Q, Dong J, Song R, Li M, Xie Y. Effects of hepatitis B virus infection and strategies for preventing mother-to-child transmission on maternal and fetal T-cell immunity. Front Immunol 2023; 14:1122048. [PMID: 36875136 PMCID: PMC9978148 DOI: 10.3389/fimmu.2023.1122048] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Accepted: 01/31/2023] [Indexed: 02/18/2023] Open
Abstract
One of the most common routes of chronic hepatitis B virus (HBV) infection is mother-to-child transmission (MTCT). Approximately 6.4 million children under the age of five have chronic HBV infections worldwide. HBV DNA high level, HBeAg positivity, placental barrier failure, and immaturity of the fetal immune are the possible causes of chronic HBV infection. The passive-active immune program for children, which consists of the hepatitis B vaccine and hepatitis B immunoglobulin, and antiviral therapy for pregnant women who have a high HBV DNA load (greater than 2 × 105 IU/ml), are currently two of the most important ways to prevent the transmission of HBV from mother to child. Unfortunately, some infants still have chronic HBV infections. Some studies have also found that some supplementation during pregnancy can increase cytokine levels and then affect the level of HBsAb in infants. For example, IL-4 can mediate the beneficial effect on infants' HBsAb levels when maternal folic acid supplementation. In addition, new research has indicated that HBV infection in the mother may also be linked to unfavorable outcomes such as gestational diabetes mellitus, intrahepatic cholestasis of pregnancy, and premature rupture of membranes. The changes in the immune environment during pregnancy and the hepatotropic nature of HBV may be the main reasons for the adverse maternal outcomes. It is interesting to note that after delivery, the women who had a chronic HBV infection may spontaneously achieve HBeAg seroconversion and HBsAg seroclearance. The maternal and fetal T-cell immunity in HBV infection is important because adaptive immune responses, especially virus-specific CD8 T-cell responses, are largely responsible for viral clearance and disease pathogenesis during HBV infection. Meanwhile, HBV humoral and T-cell responses are important for the durability of protection after fetal vaccination. This article reviews the literature on immunological characteristics of chronic HBV-infected patients during pregnancy and postpartum, blocking mother-to-child transmissions and related immune mechanisms, hoping to provide new insights for the prevention of HBV MTCT and antiviral intervention during pregnancy and postpartum.
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Affiliation(s)
- Huihui Lu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Department of Obstetrics and Gynecology, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Weihua Cao
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Department of Infectious Diseases, Miyun Teaching Hospital, Capital Medical University, Beijing, China
| | - Luxue Zhang
- Infectious Disease Department, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Liu Yang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xiaoyue Bi
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yanjie Lin
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
| | - Wen Deng
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Tingting Jiang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Fangfang Sun
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Zhan Zeng
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
| | - Yao Lu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Lu Zhang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ruyu Liu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yuanjiao Gao
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Shuling Wu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Hongxiao Hao
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xiaoxue Chen
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Leiping Hu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Mengjiao Xu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Qiqiu Xiong
- Department of General Surgery, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Jianping Dong
- Department of Infectious Disease, Haidian Hospital, Beijing Haidian Section of Peking University Third Hospital, Beijing, China
| | - Rui Song
- Department of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Minghui Li
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
| | - Yao Xie
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
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Wu S, Wang X, Feng M, Liu X, Fan X, Ran X, Wang B, Wang H. Safety and immunogenicity of inactivated COVID-19 vaccine CoronaVac and the RBD-dimer-based COVID-19 vaccine ZF2001 in chronic hepatitis B patients. Front Med (Lausanne) 2023; 10:1078666. [PMID: 36844234 PMCID: PMC9944390 DOI: 10.3389/fmed.2023.1078666] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 01/17/2023] [Indexed: 02/10/2023] Open
Abstract
Background and aims Although COVID-19 vaccination is recommended for the patients with chronic liver disease, the clinical outcomes of COVID-19 vaccinated in patients with chronic hepatitis B (CHB) has not been well characterized. The study aimed to explore the safety and specific antibody responses following COVID-19 vaccination among CHB patients. Methods Patients with CHB were included. All patients were vaccinated with two doses of inactivated vaccine (CoronaVac) or three doses of adjuvanted protein subunit vaccine (ZF2001). The adverse events were recorded and neutralizing antibody (NAb) were determined 14 days following the whole-course vaccination. Results A total of 200 patients with CHB were included. Specific NAb against SARS-CoV-2 were positive in 170 (84.6%) patients. The median (IQR) concentrations of NAb were 16.32 (8.44-34.10) AU/ml. Comparison of immune responses between CoronaVac and ZF2001 vaccines showed no significant differences in neither the concentrations of NAb nor the seropositive rates (84.4 vs. 85.7%). Moreover, we observed lower immunogenicity in older patients and in patients with cirrhosis or underlying comorbidities. The incidences of adverse events were 37 (18.5%) with the most common adverse event as injection side pain [25 (12.5%)], followed by fatigue [15 (7.5%)]. There were no differences in the frequencies of adverse between CoronaVac and ZF2001 (19.3% vs. 17.6%). Almost all of the adverse reactions were mild and self-resolved within a few days after vaccination. Severe adverse events were not observed. Conclusions COVID-19 vaccines, CoronaVac and ZF2001 had a favorable safety profile and induced efficient immune response in patients with CHB.
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Affiliation(s)
- Shiheng Wu
- Department of Infectious Diseases, Fuyang People's Hospital, Fuyang, China
| | - Xiaolin Wang
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Mingyang Feng
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaoman Liu
- Department of Infectious Diseases, Fuyang People's Hospital, Fuyang, China
| | - Xinxing Fan
- Department of Infectious Diseases, Fuyang People's Hospital, Fuyang, China
| | - Xiangui Ran
- Department of Respiratory and Critical Care Medicine, Fuyang People's Hospital, Fuyang, China,Xiangui Ran ✉
| | - Baogui Wang
- Department of Infectious Diseases, Fuyang People's Hospital, Fuyang, China,Baogui Wang ✉
| | - Hui Wang
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China,*Correspondence: Hui Wang ✉
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Bi X, Xie S, Wu S, Cao W, Lin Y, Yang L, Jiang T, Deng W, Wang S, Liu R, Gao Y, Shen G, Chang M, Hao H, Xu M, Chen X, Hu L, Lu Y, Zhang L, Xie Y, Li M. Changes of natural killer cells' phenotype in patients with chronic hepatitis B in intermittent interferon therapy. Front Immunol 2023; 14:1116689. [PMID: 36793722 PMCID: PMC9922744 DOI: 10.3389/fimmu.2023.1116689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 01/09/2023] [Indexed: 01/31/2023] Open
Abstract
Background To investigate the changes of natural killer (NK) cell phenotype in the interferon alpha (IFN-α) treatment of chronic hepatitis B (CHB) and its relationship with clinical indicators. Methods The CHB patients who did not receive any antiviral treatment were set as initial treatment group and used pegylated interferon alpha (PEG-IFN α). Peripheral blood samples were collected at baseline, 4 weeks, and 12-24 weeks. For IFN-treated patients who entered the plateau were set as plateau group, and PEG-IFN α was discontinued and resumed after an interval of 12-24 weeks. Besides, we also enrolled some patients who had received oral drug for more than 6 months as oral drug group without follow up. Peripheral blood was collected during the plateau period, which was set as baseline, and after 12-24 weeks of intermittent treatment, and after 12-24 weeks of additional treatment with PEG-IFN α. The aim of the collection was to detect hepatitis B virus (HBV) virology, serology and biochemical indicators, and the NK cell related phenotype was detected by flow cytometry. Results In the plateau group, subgroup of CD69+CD56dim was higher with statistical significance when comparing with the initial treatment group and oral drug group [10.49 (5.27, 19.07) vs 5.03 (3.67, 8.58), Z = -3.11, P = 0.002; 10.49 (5.27, 19.07) vs 4.04 (1.90, 7.26), Z = -5.30, P < 0.001)]. CD57+CD56dim was significantly lower than that in initial treatment group and oral drug group respectively [68.42±10.37 vs 55.85±12.87, t = 5.84, P < 0.001; 76.38±9.49 vs 55.85±12.87, t = -9.65, P < 0.001]. The CD56brightCD16- subgroup in the plateau group was higher with statistical significance compared with initial treatment group and oral drug group respectively [11.64 (6.05, 19.61) vs 3.58 (1.94, 5.60), Z = -6.35, P < 0.001; 11.64 (6.05, 19.61) vs 2.37 (1.70, 4.30), Z = -7.74, P < 0.001)]. CD57+CD56dim in the plateau group had a significant higher percentage than that at baseline after IFN discontinuation for 12-24 weeks (55.85±12.87 vs 65.95±12.94, t = -2.78, P = 0.011). Conclusion During the long-term treatment of IFN, the killer subgroup of NK cells is continuously depleted, leading to the differentiation of the regulatory subgroup into the killer subgroup. In the killing subgroup, although the number is continuously depleted, the activity of the subgroup is continuously increased. In the plateau phase, after stopping IFN for a period of time, the number of NK cell subsets would gradually recover, but was still lower than that in the initial treatment group.
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Affiliation(s)
- Xiaoyue Bi
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Si Xie
- Division of Hepatology, Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Shuling Wu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Weihua Cao
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China,Department of Infectious Diseases, Miyun Teaching Hospital, Capital Medical University, Beijing, China
| | - Yanjie Lin
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
| | - Liu Yang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Tingting Jiang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Wen Deng
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Shiyu Wang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ruyu Liu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yuanjiao Gao
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ge Shen
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Min Chang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Hongxiao Hao
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Mengjiao Xu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xiaoxue Chen
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Leiping Hu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yao Lu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Lu Zhang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yao Xie
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China,Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
| | - Minghui Li
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China,Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China,*Correspondence: Minghui Li,
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Lin Y, Shen G, Xie S, Bi X, Lu H, Yang L, Jiang T, Deng W, Wang S, Zhang L, Lu Y, Gao Y, Hao H, Wu S, Liu R, Chang M, Xu M, Hu L, Chen X, Huang R, Li M, Xie Y. Dynamic changes of the proportion of HLA-DR and CD38 coexpression subsets on T lymphocytes during IFN-based chronic hepatitis B treatment. Front Immunol 2023; 13:1116160. [PMID: 36761161 PMCID: PMC9902929 DOI: 10.3389/fimmu.2022.1116160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 12/21/2022] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND To investigate the changes of human leukocyte antigen DR (HLA-DR) and CD38 coexpression subsets on T lymphocytes following interferon (IFN) therapy for those who have chronic hepatitis B (CHB). METHODS A prospective cohort of CHB patients participated in this study. CHB patients without IFN treatment (including naïve and nucleoside [nucleotide] analogs [NAs]-treated patients) were given pegylated interferon alfa (Peg-IFNα) treatment. Peripheral blood samples were taken at baseline, 4 weeks and 12-24 weeks of Peg-IFNα treatment. For the patients who entered the Peg-IFNα plateau phase due to the stagnation of the decrease in HBsAg, and Peg-IFNα was discontinued and Peg-IFNα therapy was resumed after an interval of 12-24 weeks. During the interval, they received first-line NAs treatment. Peripheral blood samples were collected at the baseline of the plateau phase, 12-24 weeks of intermittent treatment, and 12-24 weeks of Peg-IFNα retreatment. The peripheral blood samples were taken to determine virological, serological and biochemical indices of hepatitis B virus (HBV), and T lymphocyte related phenotypes were detected using flow cytometry. RESULTS In the process of long-term treatment of Peg-IFNα, the percentage of HLA-DR+CD38dim subsets increased significantly at first, then decreased gradually, while the percentage of HLA-DR+CD38hi subsets markedly increased. During long-term Peg-IFNα treatment, there was a considerable negative correlation between HBsAg and the HLA-DR+CD38hi subset percentage. The persistent high proportion of HLA-DR+CD38hi subsets was related to the occurrence of Peg-IFNα plateau phase. After Peg-IFNα intermittent treatment, the percentage of HLA-DR+CD38hi subsets decreased significantly. After Peg-IFNα retreatment, the level of HBsAg began to decrease again. At the same time, the percentage of HLA-DR+CD38hi subsets significantly increased, but it was still lower than that at the baseline level. CONCLUSIONS The spectrum of HLA-DR and CD38 coexpression subsets on T lymphocytes changed during the long-term treatment of IFN. The establishment of the IFN plateau phase was linked to the persistence of a considerable proportion of HLA-DR+CD38hi subsets on T lymphocytes. IFN intermittent treatment could significantly reduce the proportion of HLA-DR+CD38hi subsets, helping regain the antiviral efficacy of IFN during IFN retreatment.
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Affiliation(s)
- Yanjie Lin
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
| | - Ge Shen
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Si Xie
- Division of Hepatology, Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Xiaoyue Bi
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Huihui Lu
- Department of Obstetrics and Gynecology, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Liu Yang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Tingting Jiang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Wen Deng
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Shiyu Wang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Lu Zhang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yao Lu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yuanjiao Gao
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Hongxiao Hao
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Shuling Wu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ruyu Liu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Min Chang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Mengjiao Xu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Leiping Hu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xiaoxue Chen
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ronghai Huang
- Department of General Surgery, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Minghui Li
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yao Xie
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
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Wang WX, Jia R, Jin XY, Li X, Zhou SN, Zhang XN, Zhou CB, Wang FS, Fu J. Serum cytokine change profile associated with HBsAg loss during combination therapy with PEG-IFN-α in NAs-suppressed chronic hepatitis B patients. Front Immunol 2023; 14:1121778. [PMID: 36756119 PMCID: PMC9899895 DOI: 10.3389/fimmu.2023.1121778] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Accepted: 01/09/2023] [Indexed: 01/24/2023] Open
Abstract
Objective The aim of this study was to explore the profile of cytokine changes during the combination therapy with pegylated interferon alpha (PEG-IFN-α) and its relationship with HBsAg loss in nucleos(t)ide analogs (NAs)-suppressed chronic hepatitis B patients. Methods Seventy-six patients with chronic hepatitis B with HBsAg less than 1,500 IU/ml and HBV DNA negative after receiving ≥ 1-year NAs therapy were enrolled. Eighteen patients continued to take NAs monotherapy (the NAs group), and 58 patients received combination therapy with NAs and PEG-IFN-α (the Add-on group). The levels of IFNG, IL1B, IL1RN, IL2, IL4, IL6, IL10, IL12A, IL17A, CCL2, CCL3, CCL5, CXCL8, CXCL10, TNF, and CSF2 in peripheral blood during treatment were detected. Results At week 48, 0.00% (0/18) in the NAs group and 25.86% (15/58) in the Add-on group achieved HBsAg loss. During 48 weeks of combined treatment, there was a transitory increase in the levels of ALT, IL1RN, IL2, and CCL2. Compared to the NAs group, CXCL8 and CXCL10 in the Add-on group remain higher after rising, yet CCL3 showed a continuously increasing trend. Mild and early increases in IL1B, CCL3, IL17A, IL2, IL4, IL6, and CXCL8 were associated with HBsAg loss or decrease >1 log, while sustained high levels of CCL5 and CXCL10 were associated with poor responses to Add-on therapy at week 48. Conclusions The serum cytokine change profile is closely related to the response to the combination therapy with PEG-IFN-α and NAs, and may help to reveal the mechanism of functional cure and discover new immunological predictors and new therapeutic targets.
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Affiliation(s)
- Wen-Xin Wang
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Peking University 302 Clinical Medical School, National Clinical Research Center for Infectious Diseases, Beijing, China
| | - Rui Jia
- Department of Gastroenterology, The 985th Hospital of Joint Logistic Support Force of Chinese PLA, Taiyuan, China
| | - Xue-Yuan Jin
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Peking University 302 Clinical Medical School, National Clinical Research Center for Infectious Diseases, Beijing, China
| | - Xiaoyan Li
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Peking University 302 Clinical Medical School, National Clinical Research Center for Infectious Diseases, Beijing, China,Medical School of Chinese PLA, Beijing, China
| | - Shuang-Nan Zhou
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Peking University 302 Clinical Medical School, National Clinical Research Center for Infectious Diseases, Beijing, China
| | - Xiao-Ning Zhang
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Peking University 302 Clinical Medical School, National Clinical Research Center for Infectious Diseases, Beijing, China
| | - Chun-Bao Zhou
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Peking University 302 Clinical Medical School, National Clinical Research Center for Infectious Diseases, Beijing, China
| | - Fu-Sheng Wang
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Peking University 302 Clinical Medical School, National Clinical Research Center for Infectious Diseases, Beijing, China,Medical School of Chinese PLA, Beijing, China,*Correspondence: Junliang Fu, ; Fu-Sheng Wang,
| | - Junliang Fu
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Peking University 302 Clinical Medical School, National Clinical Research Center for Infectious Diseases, Beijing, China,Medical School of Chinese PLA, Beijing, China,*Correspondence: Junliang Fu, ; Fu-Sheng Wang,
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Gao S, Li J, Yang X, Yang Y, Jia T, Zhang X, Gao J. Predictive Values of Programmed Death-1, CC Chemokine Ligand 20, and Treg/T Helper 17 Cytokines for Patients with Hepatitis B Virus-Related Acute-on-Chronic Liver Failure. HEPATITIS MONTHLY 2023; 22. [DOI: 10.5812/hepatmon-127376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 12/10/2022] [Accepted: 12/10/2022] [Indexed: 01/03/2025]
Abstract
Background: This study aimed to explore the correlations of programmed death-1 (PD-1) and CC chemokine ligand 20 (CCL20) with Treg/T helper 17 (Th17) balance in patients with HBV-ACLF. Methods: In this cross-sectional study, 50 patients with HBV-ACLF and 50 cases with chronic hepatitis B (CHB) diagnosed from February 2021 to February 2022 were selected, and another 50 healthy volunteers who received physical examinations in the same period were selected as a control group. The expression levels of PD-1, CCL20, and Treg/Th17 cytokines were detected by Western blotting, immunoturbidimetry, and enzyme-linked immunosorbent assay (ELISA), respectively. The correlations of PD-1 and CCL20 with Treg/Th17 cytokines were explored by Pearson analysis. The predictive values of PD-1, CCL20, and Treg/Th17 cytokines for the prognosis of HBV-ACLF patients were analyzed. Results: The expression levels of PD-1 and CCL20 were higher in the HBV-ACLF group than in the CHB and control groups (P < 0.05). Severe HBV-ACLF patients had higher levels of PD-1 and CCL20 compared with mild and moderate HBV-ACLF patients (P < 0.05). Hepatitis B virus-related acute-on-chronic liver failure patients with poor prognosis had higher levels of PD-1 and CCL20 than those with good prognosis (P < 0.05). The levels of transforming growth factor β (TGF-β), interleukin 10 (IL-10), IL-23, and tumor necrosis factor α (TNF-α) were higher in the HBV-ACLF group than in the CHB and control groups (P < 0.05). The levels of PD-1 and CCL20 in the HBV-ACLF group were positively correlated with those of Treg/Th17 cytokines (TGF-β, IL-10, IL-23, and TNF-α; P < 0.05). The combined detection of PD-1, CCL20, and Treg/Th17 cytokines had higher sensitivity and lower specificity than single detection in predicting the prognosis of HBV-ACLF patients (P < 0.05). Conclusions: The expression levels of PD-1 and CCL20 are higher in HBV-ACLF patients, being correlated with Treg/Th17 balance. The combined detection of PD-1, CCL20, and Treg/Th17 cytokines has a higher value for predicting the prognosis of HBV-ACLF patients.
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Li H, Liang S, Liu L, Zhou D, Liu Y, Zhang Y, Chen X, Zhang J, Cao Z. Clinical cure rate of inactive HBsAg carriers with HBsAg <200 IU/ml treated with pegylated interferon. Front Immunol 2022; 13:1091786. [PMID: 36618361 PMCID: PMC9822570 DOI: 10.3389/fimmu.2022.1091786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Accepted: 12/06/2022] [Indexed: 12/24/2022] Open
Abstract
Purpose HBsAg clearance represents clinical cure for patients with hepatitis B, but remains difficult to obtain for most HBV-infected patients. Recent studies have shown that inactive HBsAg carriers treated with pegylated interferon can achieve higher clinical cure rates, which may imply that the lower the baseline HBsAg quantification, the higher HBsAg clearance rate. Therefore, this study further investigated the HBsAg clearance rate in inactive HBsAg carriers with low level of HBsAg (<200 IU/ml) treated with pegylated interferon. Methods This is a prospective cohort study. Inactive HBsAg carriers with HBsAg<200 IU/ml were divided into treatment and control groups. Pegylated interferon was administered to the patients in therapeutic group for 96 weeks. The patients in control group underwent 96 weeks of observation without any anti-viral treatment. All patients were tested for HBsAg, anti-HBs, HBV DNA, liver function, blood count, thyroid function, thyroid antibodies and autoantibodies at baseline, week 12, 24, 36, 48, 60, 72, 84 and 96. Controlled attenuation parameter (CAP) and liver stiffness measure (LSM) were evaluated at baseline and week 96. Patients were classified into no steatosis, mild steatosis, moderate steatosis and severe steatosis according to the value of CAP. Results A total of 174 inactive HBsAg carriers with HBsAg<200IU/ml were enrolled, including 84 in the treatment group and 90 in the control group. In the treatment group, HBsAg clearance rate was 30.77% (24/78) at week 48, and increased to 57.69% (45/78) at week 96. HBsAg clearance occurred in 2 patients with a clearance rate of 2.27% (2/88) in control group, The HBsAg clearance rate of the treatment group was significantly higher than that of the control group (P<0.001). HBsAg clearance was significantly higher in patients with moderate steatosis than in those without steatosis (74.07% vs. 48.15%, p=0.008) at week 96. Conclusion High HBsAg clearance rate could be obtained for inactive HBsAg carriers with HBsAg< 200 IU/ml treated with peginterferons. Inactive HBsAg carriers with moderate hepatic steatosis are more sensitive for the treatment.
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Affiliation(s)
- Hong Li
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Shan Liang
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Lili Liu
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Daqiong Zhou
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Yali Liu
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Yang Zhang
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Xinyue Chen
- The First Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Jing Zhang
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China,*Correspondence: Zhenhuan Cao, ; Jing Zhang,
| | - Zhenhuan Cao
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China,*Correspondence: Zhenhuan Cao, ; Jing Zhang,
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Guo X, Ji T, Xin S, Xu J, Yu Y. A case report of hepatitis B virus reactivation 19 months after cessation of chemotherapy with rituximab. Front Immunol 2022; 13:1083862. [PMID: 36532005 PMCID: PMC9755885 DOI: 10.3389/fimmu.2022.1083862] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Accepted: 11/21/2022] [Indexed: 12/05/2022] Open
Abstract
A 72-year-old woman presented to our hospital with elevation of serum transaminases. Her blood tests showed the hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) negative. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were given for the diffuse large B-cell lymphoma. She didn't receive anti- hepatitis B virus (HBV) drug for the isolated HBcAb positive. HBV reactivation confirmed based on the serum HBV DNA detectable until 19 months after stopping R-CHOP regimen. HBV DNA became undetectable after 4 weeks therapy with Tenofovir alafenamide fumarate (TAF). Serum transaminases went down to normal 3 months later after receiving TAF. HBV reactivation is a substantial risk for patients with isolated HBcAb positive receiving rituximab-containing chemotherapy without anti- HBV drug. Regular monitoring with a frequency of 1-3 months is the basis for timely diagnosis and treatment of HBV reactivation. Serum transaminases abnormalities may be the initial manifestation of HBV reactivation.
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Affiliation(s)
- Xiangjuan Guo
- Department of Infectious Diseases, Peking University First Hospital, Beijing, China,Department of Infectious Diseases, Handan Central Hospital, Handan, China
| | - Tongtong Ji
- Department of Infectious Diseases, Peking University First Hospital, Beijing, China
| | - Shengliang Xin
- Department of Infectious Diseases, Peking University First Hospital, Beijing, China
| | - Jinghang Xu
- Department of Infectious Diseases, Peking University First Hospital, Beijing, China,*Correspondence: Yanyan Yu, ; Jinghang Xu,
| | - Yanyan Yu
- Department of Infectious Diseases, Peking University First Hospital, Beijing, China,*Correspondence: Yanyan Yu, ; Jinghang Xu,
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Yan Y, Sun H, Chang L, Ji H, Jiang X, Song S, Xiao Y, Feng K, Nuermaimaiti A, Lu Z, Wang L. Circulating immune complexes and mutations of HBsAg are associated with the undetectable HBsAg in anti-HBs and HBeAg positive occult hepatitis B virus infection. Front Microbiol 2022; 13:1063616. [DOI: 10.3389/fmicb.2022.1063616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Accepted: 11/14/2022] [Indexed: 11/30/2022] Open
Abstract
IntroductionOccult hepatitis B virus infection (OBI) is an HBsAg negative state in HBV infection with usually inactive HBV replication. However, there were a minority of individuals with positive HBeAg and anti-HBs among OBI blood donors and few studies have focused on this unusual serological pattern.Methods2022 plasma of blood donors that preliminary screened reactive for HBV DNA and non-reactive for HBsAg were collected from 16 provinces in China from 2015 to 2018. HBV DNA and HBsAg in these samples were retested using the Cobas TaqScreen MPX test and ARCHITECT HBsAg Quantitative II assay. Lumipulse HBsAg-HQ assay and polyethylene glycol (PEG)-double precipitation following HCl and trypsin digestion were performed to detect HBsAg from HBsAg-anti-HBs circulating immune complexes (CICs).Results1487 of 2022 samples were positive for Cobas HBV DNA test and non-reactive for ARCHITECT HBsAg assay, while 404 of them were positive using Lumipulse HBsAg-HQ assay. 10 HBsAg-/anti-HBs+/HBeAg+ OBI blood donor samples were further dissociated and HBsAg-CICs were detected in 7 samples. Sequencing analysis showed that D44N, N98T, G73S, Del 56-116, and I161T occurred in the pre-S region, and immune escape mutations such as P127T, F134L, G145R, V168A, and I126T/S in the S region were found.DiscussionIn conclusion, there were a minority of HBsAg-/anti-HBs+/HBeAg+ individuals in OBI blood donors. The undetectable HBsAg in these individuals was mainly due to HBsAg-CICs. Immune escape-associated mutations also happened under the host’s selective pressure. HBsAg dissociation methods or Lumipulse HBsAg-HQ assay is recommended to distinguish these individuals.
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Sun F, Li Z, Hu L, Deng W, Jiang T, Wang S, Bi X, Lu H, Yang L, Lin Y, Zeng Z, Shen G, Liu R, Chang M, Wu S, Gao Y, Hao H, Xu M, Chen X, Zhang L, Lu Y, Dong J, Xie Y, Li M. Sustained viral response and relapse after discontinuation of oral antiviral drugs in HBeAg-positive patients with chronic hepatitis B infection. Front Immunol 2022; 13:1082091. [PMID: 36505492 PMCID: PMC9732422 DOI: 10.3389/fimmu.2022.1082091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Accepted: 11/11/2022] [Indexed: 11/26/2022] Open
Abstract
OBJECTIVE To investigate the sustained virological response and relapse in chronic hepatitis B (CHB) patients with hepatitis B e antigen (HBeAg) positive after stopping oral antiviral drugs, and to monitor the disease progression and the incidence of adverse events such as liver cirrhosis and hepatocellular carcinoma. METHODS This is a prospective observational study. Patients who continued nucleos(t)ide analogue (NA) treatment after achieving HBeAg seroconversion for more than 3 years were enrolled. After signing the informed consent form, patients stopped NA treatment and received follow-up. During the follow-up, the antiviral treatment information of the patients was collected, and the follow-up observation was carried out every 3 months since the enrollment. We monitored the virological indexes, liver and kidney function, serology and liver imaging during follow-up. The purpose of this study was to explore the sustained virological response rate, HBV DNA recurrence rate, clinical relapse rate and the related factors after drug withdrawal. RESULTS A total of 82 patients were enrolled, including 42 males (51.22%) and 40 females (48.78%), with a median age of 34.00 (31.00, 37.25) years. All enrolled patients were followed up for 1 year. At the end of the follow-up, 36.59% (30/82) of patients had sustained virological response, 63.41% (52/82) of patients had HBV DNA reactivation, 17.07% (14/82) of patients had clinical relapse, and 10.98% (9/82) of patients had HBeAg reversion. During the follow-up, there were no adverse events such as liver cirrhosis and hepatocellular carcinoma. The median level of hepatitis B surface antigen (HBsAg) in patients with sustained virological response was lower than that in patients with HBV DNA reactivation (2.92 vs.3.18 log10IU/ml, Z=-1.492/P=0.136), and the median level of baseline HBsAg in patients with HBV DNA reactivation was lower than that in patients with clinical relapse (3.01 vs.3.45 log10IU/mL, Z=-1.795/P=0.073), but the difference was not significant. There was no significant statistical difference between patients with sustained virological response and HBV DNA reactivation of the median total treatment time [69.50 (56.25, 86.00) vs.62.50 (44.00, 88.50) months, Z=-0.689/P=0.491], and the consolidation treatment time [41.50 (36.75, 54.75) vs.40.50 (36.00, 53.75) months, Z=-0.419/P=0.675]. CONCLUSION The sustained virological response rate of HBeAg positive CHB patients after stopping oral antiviral treatment is lower, and it is more common in patients with lower HBsAg levels. Patients still need to be closely monitored after stopping NA therapy.
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Affiliation(s)
- Fangfang Sun
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Department of Infectious Diseases, Haidian Hospital, Beijing Haidian Section of Peking University Third Hospital, Beijing, China
| | - Zhenhua Li
- Department of Gynecology and Obstetrics, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Leiping Hu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Wen Deng
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Tingting Jiang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Shiyu Wang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xiaoyue Bi
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Huihui Lu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Department of Obstetrics and Gynecology, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Liu Yang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yanjie Lin
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
| | - Zhan Zeng
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
| | - Ge Shen
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ruyu Liu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Min Chang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Shuling Wu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yuanjiao Gao
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Hongxiao Hao
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Mengjiao Xu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xiaoxue Chen
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Lu Zhang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yao Lu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Jianping Dong
- Department of Infectious Diseases, Haidian Hospital, Beijing Haidian Section of Peking University Third Hospital, Beijing, China
| | - Yao Xie
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
| | - Minghui Li
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
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Zeng Z, Hao H, Bi X, Lin Y, Yang L, Wang S, Shen G, Chang M, Jiang T, Deng W, Lu H, Sun F, Lu Y, Gao Y, Liu R, Xu M, Chen X, Hu L, Zhang L, Li M, Xie Y. Study on liver histopathology of chronic HBV infected patients with different normal ALT values. Front Immunol 2022; 13:1069752. [PMID: 36483546 PMCID: PMC9725112 DOI: 10.3389/fimmu.2022.1069752] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Accepted: 11/08/2022] [Indexed: 11/23/2022] Open
Abstract
AIMS Comparison of liver histopathological findings to explore the occurrence of liver inflammation in patients with chronic hepatitis B (CHB) under different alanine aminotransferase (ALT) normal values. METHODS The patients who were diagnosed as chronic hepatitis B virus (HBV) infection by liver histopathology at the Department of Pathology, Beijing Ditan Hospital due to clinical difficulty in defining the degree of liver inflammation or fibrosis were retrospectively enrolled from May 2008 to November 2020. Study of the incidence of significant hepatic histopathology in enrolled patients according to different ALT normal values. Using logistic regression to investigate the relevant factors of significant hepatic histopathology. RESULTS A total of 1474 patients were enrolled, 56.20% of the patients were male, and the overall patients' age was 36.80 ± 10.60 years. 39.00% of patients had liver inflammation grade G > 1, 34.70% liver fibrosis stage S > 1, and 48.17% patients had significant hepatic histopathology (G > 1 and/or S > 1). Among patients with normal ALT values, 36.40% and 40.40% had significant hepatic histopathology by American Association for the Study of Liver Diseases (AASLD) criteria and Chinese guideline criteria, respectively, but the difference was not statistically significant (χ2 = 3.38, P =0.066). In contrast, among patients with abnormal ALT values, 58.90% and 62.20% of patients had significant hepatic histopathology by AASLD criteria and Chinese guideline criteria, respectively, with no significant difference (χ2 = 2.28, P =0.131). ALT (P <0.001, OR=1.019), hepatitis B surface antigen (HBsAg) (P <0.001, OR=0.665) and hepatitis B e antigen (HBeAg) status (P <0.001, OR=2.238) were relevant factors in the occurrence of significant hepatic histopathology. ALT was positively corelated with grade of inflammation G (r =0.194, P <0.001) and negatively correlated with liver fibrosis stage S (r =-0.066, P =0.021). CONCLUSIONS Our study found no statistically significant differences in the presence of significant hepatic histopathology under the two ALT criteria. ALT, HBsAg and HBeAg status were related to the occurrence of significant hepatic histopathology.
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Affiliation(s)
- Zhan Zeng
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Department of Infectious Diseases, Peking University First Hospital, Beijing, China
| | - Hongxiao Hao
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xiaoyue Bi
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yanjie Lin
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
| | - Liu Yang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Shiyu Wang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ge Shen
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Min Chang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Tingting Jiang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Wen Deng
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Huihui Lu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Fangfang Sun
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yao Lu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yuanjiao Gao
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ruyu Liu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Mengjiao Xu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xiaoxue Chen
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Leiping Hu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Lu Zhang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Minghui Li
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
| | - Yao Xie
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
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Zheng JR, Wang ZL, Feng B. Hepatitis B functional cure and immune response. Front Immunol 2022; 13:1075916. [PMID: 36466821 PMCID: PMC9714500 DOI: 10.3389/fimmu.2022.1075916] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Accepted: 11/02/2022] [Indexed: 07/30/2023] Open
Abstract
Hepatitis B virus (HBV) is a hepatotropic virus, which damage to hepatocytes is not direct, but through the immune system. HBV specific CD4+ T cells can induce HBV specific B cells and CD8+ T cells. HBV specific B cells produce antibodies to control HBV infection, while HBV specific CD8+ T cells destroy infected hepatocytes. One of the reasons for the chronicity of HBV infection is that it cannot effectively activate adoptive immunity and the function of virus specific immune cells is exhausted. Among them, virus antigens (including HBV surface antigen, e antigen, core antigen, etc.) can inhibit the function of immune cells and induce immune tolerance. Long term nucleos(t)ide analogues (NAs) treatment and inactive HBsAg carriers with low HBsAg level may "wake up" immune cells with abnormal function due to the decrease of viral antigen level in blood and liver, and the specific immune function of HBV will recover to a certain extent, thus becoming the "dominant population" for functional cure. In turn, the functional cure will further promote the recovery of HBV specific immune function, which is also the theoretical basis for complete cure of hepatitis B. In the future, the complete cure of chronic HBV infection must be the combination of three drugs: inhibiting virus replication, reducing surface antigen levels and specific immune regulation, among which specific immunotherapy is indispensable. Here we review the relationship, mechanism and clinical significance between the cure of hepatitis B and immune system.
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Affiliation(s)
| | | | - Bo Feng
- Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University People’s Hospital, Peking University Hepatology Institute, Beijing, China
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Virological Changes of Chronic Hepatitis B Patients with Minimally Elevated Levels of Alanine Aminotransferase: A Meta-Analysis and Systematic Review. Can J Gastroenterol Hepatol 2022; 2022:7499492. [PMID: 36439633 PMCID: PMC9683979 DOI: 10.1155/2022/7499492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 10/17/2022] [Accepted: 11/02/2022] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Chronic hepatitis B (CHB) patients with normal or minimally increased levels of alanine aminotransferase (ALT) are still at the risk of hepatocellular carcinoma, cirrhotic events, and mortality. However, there is a debate over the initiation of antiviral treatment for these patients. This systematic review and mate-analysis aimed to explore this problem. METHODS MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science databases were systematically searched for retrieving relevant studies with risk ratios (RRs) or risk differences (RDs) for virological changes between antivirus-treated and no antivirus-treated CHB patients with ALT levels less than two-fold of the upper limit of normal. Retrieved data ranged from January 1990 to October 2020. RESULTS Of 6783 abstracts screened, 9 studies met the criteria for inclusion in the systematic review and had a low risk of bias. Among studies that were involved in the meta-analyses, it was found that the rates of HBsAg loss (RR = 12.22, 95% confidence interval (CI): 4.28-34.95, P < 0.001), HBsAg seroconversion (RR = 19.90, 95% CI: 2.75-144.09, P=0.003), and undetectable HBV DNA (RR = 11.89, 95% CI: 2.44-57.89, P=0.002) were both higher in the antiviral treatment group compared with placebo or no treatment group. Subgroup analysis suggested that patients who received interferon (IFN)-based therapy were more inclined to achieve HBsAg loss (P=0.010), HBsAg seroconversion (P=0.020), and HBeAg loss (P=0.002). CONCLUSION From a sizable population, it was revealed that CHB patients with normal or minimally increased levels of ALT could benefit from the antiviral therapy, especially those who received IFN-based treatment.
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Qian Z, Hu M, Wu H, Chen H, Liao G, Kang Z, Lin X, Peng J. The Efficacy of Antiviral Treatment for Chronic Hepatitis B Patients with Normal ALT Levels: A Systematic Review and Meta-analysis. HEPATITIS MONTHLY 2022; 22. [DOI: 10.5812/hepatmon-129836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 10/03/2022] [Accepted: 10/06/2022] [Indexed: 01/04/2025]
Abstract
Context: When nucleos(t)ide analogues (NAs) were applied clinically to manage chronic hepatitis B virus infection, the prognosis of chronic hepatitis B (CHB) patients greatly improved. However, certain CHB patients with normal alanine aminotransferase (ALT) levels were not used to be considered as the population with the need for antiviral treatment. Objectives: This systematic review and meta-analysis collected and analyzed data from clinical trials to assess and compare the efficacy of antiviral treatment among patients with elevated and normal ALT levels. Methods: A systematic search was performed to gather studies published from 1990.01 to 2022.08 in PubMed and Web of Science databases. The quality of the literature was assessed, and 16 studies were included for further analysis. Basic information on included studies and study populations was collected. A meta-analysis was carried out to evaluate three major outcomes of viral response, hepatitis B envelope antigen (HBeAg) loss, and HBeAg seroconversion after NAs treatment based on data extracted from these studies. Odds ratios (ORs) with 95% confidence intervals (CIs) for all outcomes were calculated using fixed-effects models. Results: In the 16 relevant studies, 5,345 patients met the inclusion criteria, including 3,687 patients receiving NAs treatment. All patients were grouped into one with elevated ALT and another with normal ALT based on whether their pretreatment ALT levels > 1*upper limit of normal (ULN). For patients receiving lamivudine, the viral response showed no significant difference between the groups with elevated and normal ALT levels (pooled log OR: 0.51 [-0.23 - 1.26], P = 0.79); the pooled log OR for HBeAg loss was 1.19 (0.63 - 1.76, P = 0.03) and pooled log OR for HBeAg seroconversion was 2.19 (0.91 - 3.47, P = 0.40). For patients receiving first-line therapy with tenofovir disoproxil fumarate (TDF) and entecavir (ETV), the viral response showed no significant difference between the two groups: Pooled log OR (0.38 [-0.22 - 0.97], P = 0.10). The pooled log OR for HBeAg loss and HBeAg seroconversion was (-0.07 [-0.81 - 0.67], P = 0.68) and (0.40 [-0.84 - 1.63], P = 0.88), respectively. Conclusions: The efficacies of first-line therapy with TDF and ETV treatments were similar in groups with elevated and normal ALT levels for the outcomes of viral response and HBeAg loss. These findings may support further treatment of CHB patients with normal ALT levels.
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Liu SQ, Zhang XJ, Xue Y, Huang R, Wang J, Wu C, He YS, Pan YR, Liu LG. Dynamic changes of estimated glomerular filtration rate are conversely related to triglyceride in non-overweight patients. World J Clin Cases 2022; 10:11371-11380. [PMID: 36387799 PMCID: PMC9649538 DOI: 10.12998/wjcc.v10.i31.11371] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 08/30/2022] [Accepted: 09/23/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Correlation between Triglyceride (TG) and estimated glomerular filtration rate (eGFR) remains largely unknown in overweight and non-overweight patients.
AIM To investigated the dynamic changes of eGFR and lipid profiles during 3-year tenofovir disoproxil fumarate (TDF) treatment in patients with chronic hepatitis B (CHB) and overweight.
METHODS A total of 202 CHB patients who received TDF treatment at the Third People's Hospital of Changzhou (Changzhou, China) and Nanjing Drum Tower Hospital (Nanjing, China) between January 2016 and May 2018 were retrospectively enrolled. According to the body mass index (BMI) at the initiation of TDF treatment, CHB patients were divided into overweight (BMI ≥ 25 kg/m2) and non-overweight (BMI < 25 kg/m2) groups. Logistic regression was applied for the analysis of risk factors for eGFR < 90 mL/(min·1.73 m2).
RESULTS There is no significant difference in hepatitis B virus DNA (HBV DNA) negativity and hepatitis Be antigen (HBeAg) loss between patients with overweight and non-overweight (both P > 0.05). More patients in non-overweight group achieved alanine aminotransferase normalization compared with those in overweight group (χ2 = 11.036, P < 0.01). In non-overweight patients, the eGFR significantly declined in the 1st year (P < 0.01), then remained at a relatively lower level. TG significantly declined in the 2nd year (P = 0.02) and increased in the 3rd year. Moreover, TG was negatively correlated with GFR at the four-time points (P = 0.002, 0.030, 0.007, 0.008, respectively). In overweight patients, eGFR and TG remained relatively stable during the 3-year treatment, and eGFR showed no significant relationship with TG. Moreover, multivariate analysis showed that age [P < 0.01, 95%CI (0.97-1.005)] and baseline eGFR [P < 0.01, 95%CI (5.056-33.668)] were independent risk factors for eGFR < 90 mL/(min·1.73 m2) at the 3rd year.
CONCLUSION Dynamic changes in renal function were conversely related to TG during TDF treatment in patients with CHB and normal BMI, but not with overweight.
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Affiliation(s)
- Si-Qi Liu
- Changzhou Clinical Medical College, Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
| | - Xiu-Jun Zhang
- Institute of Hepatology, The Third People’s Hospital of Changzhou, Changzhou 213000, Jiangsu Province, China
| | - Yuan Xue
- Institute of Hepatology, The Third People’s Hospital of Changzhou, Changzhou 213000, Jiangsu Province, China
| | - Rui Huang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing 210008, Jiangsu Province, China
| | - Jian Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing 210008, Jiangsu Province, China
| | - Chao Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing 210008, Jiangsu Province, China
| | - Yi-Shan He
- Changzhou Clinical Medical College, Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
| | - Ya-Ru Pan
- Changzhou Clinical Medical College, Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
| | - Long-Gen Liu
- Institute of Hepatology, The Third People’s Hospital of Changzhou, Changzhou 213000, Jiangsu Province, China
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Sheng Q, Wang N, Zhang C, Fan Y, Li Y, Han C, Wang Z, Wei S, Dou X, Ding Y. HBeAg-negative Patients with Chronic Hepatitis B Virus Infection and Normal Alanine Aminotransferase: Wait or Treat? J Clin Transl Hepatol 2022; 10:972-978. [PMID: 36304490 PMCID: PMC9547271 DOI: 10.14218/jcth.2021.00443] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 12/25/2021] [Accepted: 02/27/2022] [Indexed: 12/04/2022] Open
Abstract
Alanine aminotransferase (ALT) is a common clinical indicator of liver inflammation. The current Chinese guidelines for the management of chronic hepatitis B (CHB) recommend antiviral treatment for patients with detectable hepatitis B virus (HBV) DNA and persistent ALT levels (ALTs) exceeding the upper limit of normal. However, it has been recently reported that patients with chronic HBV infection, especially HBeAg-negative patients with persistently normal ALTs, may have liver biopsy findings of significant inflammation and fibrosis. For HBeAg-negative patients with chronic HBV infection and normal ALTs, many controversial questions have been asked. To treat or not? When to initiate the treatment? Which drug is appropriate? In this review, we summarize the available data on the management of HBeAg-negative patients with chronic HBV infection and normal ALTs with the aim of improving the current clinical management.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Xiaoguang Dou
- Correspondence to: Xiaoguang Dou and Yang Ding, Department of Infectious Diseases, Shengjing Hospital of China Medical University, No. 39 HuaXiang Road, TieXi District,Shenyang, Liaoning 110022, China. ORCID: https://orcid.org/0000-0003-1856-7331 (XGD), https://orcid.org/0000-0002-7066-2865 (YD). Tel: +86-18940251121 (XGD), +86-13332434847 (YD), Fax: +86-24-25998744, E-mail: (XGD), (YD)
| | - Yang Ding
- Correspondence to: Xiaoguang Dou and Yang Ding, Department of Infectious Diseases, Shengjing Hospital of China Medical University, No. 39 HuaXiang Road, TieXi District,Shenyang, Liaoning 110022, China. ORCID: https://orcid.org/0000-0003-1856-7331 (XGD), https://orcid.org/0000-0002-7066-2865 (YD). Tel: +86-18940251121 (XGD), +86-13332434847 (YD), Fax: +86-24-25998744, E-mail: (XGD), (YD)
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Xu X, Wu C, Jiang L, Peng C, Pan L, Zhang X, Shen W, Chen L, Lou Z, Xu K, Li L, Dong Y, Ruan B. Cost-Effectiveness of Hepatitis B Mass Screening and Management in High-Prevalent Rural China: A Model Study From 2020 to 2049. Int J Health Policy Manag 2022; 11:2115-2123. [PMID: 34664496 PMCID: PMC9808295 DOI: 10.34172/ijhpm.2021.126] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 09/04/2021] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Chronic hepatitis B (CHB) is highly prevalent among adults in rural China and better management of those populations is of vital importance for viral hepatitis elimination. Adult immunization has been the subject of much controversy in previous studies. This study estimates the cost-effectiveness of population-based hepatitis B screening, treatment, and immunization strategy (comprehensive strategy) in rural areas with high prevalence under the national policy of sharp-drop drug prices. METHODS We constructed a Markov model comparing 4 strategies in a 30-year horizon from the healthcare payer perspective: (1) the conventional pattern; (2) screening and treating infected (treatment); (3) screening and immunizing susceptible individuals (immunization); and (4) the comprehensive strategy. Screening intensity ranged from 50% to 100%. Outcomes were measured by costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), and clinical outcomes. RESULTS The costs for the conventional pattern, treatment strategy, immunization strategy, and comprehensive strategy were US$ 341, 351, 318, and 323, respectively. In addition, effects were 17.45, 17.57, 17.46, and 17.58 QALYs, respectively. The ICER of the comprehensive strategy was US$ 35/QALY gained at 50% screening intensity and 420 US$/QALY gained at 100%. The net monetary benefit increased with increasing screening intensity and declined after 90%, with the highest value of US$40 693. All new infections and 52.5% mortality could be avoided from 2020 to 2049 if all patients were properly treated and all susceptible individuals were immunized. The results were stable within a wide range of parameters. CONCLUSION It was cost-effective to implement the mass hepatitis B screening, treatment, and immunization strategy in areas of rural China with high prevalence, and the strategy gained the most net monetary benefit at a screening intensity of 90%. Although it was impractical to fulfill 100% coverage, efforts should be made to obtain more people screened.
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Affiliation(s)
- Xiaolan Xu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Chensi Wu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Lushun Jiang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Chunting Peng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Liya Pan
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Xue Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Wei Shen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Lin Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Zhuoqi Lou
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Kaijin Xu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Yin Dong
- People’s Hospital Medical Community of Yuhuan County, Taizhou, China
| | - Bing Ruan
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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Wang MQ, Li YP, Xu M, Tian Y, Wu Y, Zhang X, Shi JJ, Dang SS, Jia XL. VCAN, expressed highly in hepatitis B virus-induced hepatocellular carcinoma, is a potential biomarker for immune checkpoint inhibitors. World J Gastrointest Oncol 2022; 14:1933-1948. [PMID: 36310697 PMCID: PMC9611428 DOI: 10.4251/wjgo.v14.i10.1933] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Revised: 07/23/2022] [Accepted: 09/12/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND As a proteoglycan, VCAN exists in the tumor microenvironment and regulates tumor proliferation, invasion, and metastasis, but its role in hepatocellular carcinoma (HCC) has not yet been elucidated. AIM To investigate the expression and potential mechanism of action of VCAN in HCC. METHODS Based on The Cancer Genome Atlas Liver Hepatocellular Carcinoma dataset, we explored the correlation between VCAN expression and clinical features, and analyzed the prognosis of patients with high and low VCAN expression. The potential mechanism of action of VCAN was explored by Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, and gene set enrichment analysis. We also explored immune cell infiltration, immune checkpoint gene expression, and sensitivity of immune checkpoint [programmed cell death protein 1 (PD-1)/cytotoxic T lymphocyte antigen 4 (CTLA4)] inhibitor therapy in patients with different VCAN expression. VCAN mRNA expression and VCAN methylation in peripheral blood were tested in 100 hepatitis B virus (HBV)-related patients (50 HCC and 50 liver cirrhosis). RESULTS VCAN was highly expressed in HCC tissues, which was associated with a poor prognosis in HCC patients. No significant difference was found in VCAN mRNA expression in blood between patients with HBV-related cirrhosis and those with HCC, but there was a significant difference in VCAN methylation between the two groups. The correlation between VCAN and infiltrations of several different tumor immune cell types (including B cells, CD8+ T cells, and eosinophils) was significantly different. VCAN was strongly related to immune checkpoint gene expression and tumor mutation burden, and could be a biomarker of sensitivity to immune checkpoint (PD1/CTLA4) inhibitors. In addition, VCAN mRNA expression was associated with hepatitis B e antigen, HBV DNA, white blood cells, platelets, cholesterol, and coagulation function. CONCLUSION High VCAN level could be a possible biomarker for poor prognosis of HCC, and its immunomodulatory mechanism in HCC warrants investigation.
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Affiliation(s)
- Mu-Qi Wang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
| | - Ya-Ping Li
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
| | - Meng Xu
- Department of General Surgery, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
| | - Yan Tian
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
| | - Yuan Wu
- Department of Critical Care Medicine, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
| | - Xin Zhang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
| | - Juan-Juan Shi
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
| | - Shuang-Suo Dang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
| | - Xiao-Li Jia
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
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Xu JH, Wang S, Zhang DZ, Yu YY, Si CW, Zeng Z, Xu ZN, Li J, Mao Q, Tang H, Sheng JF, Chen XY, Ning Q, Shi GF, Xie Q, Zhang XQ, Dai J. One hundred and ninety-two weeks treatment of entecavir maleate for Chinese chronic hepatitis B predominantly genotyped B or C. World J Clin Cases 2022; 10:10085-10096. [PMID: 36246814 PMCID: PMC9561570 DOI: 10.12998/wjcc.v10.i28.10085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 06/12/2022] [Accepted: 08/24/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Entecavir (ETV) is a potent and selective nucleotide analog with significant activity against hepatitis B virus (HBV). ETV maleate is a derivative compound of ETV and was reported to have an efficacy and safety profile that is comparable to ETV (Baraclude) when used in Chinese patients with chronic hepatitis B (CHB) in phase III clinical trials (Clinical Trials.gov number, NCT01926288) at weeks 48, 96, and 144. AIM To investigate the antiviral potency and safety of ETV maleate at week 192 in Chinese CHB patients predominantly genotyped B or C. METHODS In this double-blind study, we randomly assigned patients to receive 0.5 mg/d ETV (Group A) or ETV maleate (Group B) (ratio, 1:1), each with a placebo tablet for 48 wk. Then, all patients received open-label treatment with 0.5 mg/d ETV maleate starting at week 49. The primary efficacy endpoint was the reduction in HBV DNA levels from baseline. Secondary endpoints included the proportion of patients with undetectable HBV DNA (< 20 IU/mL), serologic response, serum alanine aminotransferase (ALT) normalization and development of resistance mutations. RESULTS Two hundred eighteen patients who were hepatitis B e antigen (HBeAg) positive and 57 who were HBeAg negative were analyzed and predominantly presented with genotype B (49.82%) or C (48.73%). For the HBeAg-positive CHB patients, the mean HBV DNA level decrease (6.61 Log10 IU/mL vs 6.69 Log10 IU/mL, P > 0.05), viral suppression with HBV DNA < 20 IU/mL (83.33% vs 79.17%, P > 0.05) and HBeAg seroconversion (28.77% vs 20.00%, P > 0.05) occurred similarly between Groups A and B at week 192. However, there was a significant difference in the proportion of patients with normal ALT levels (91.14% vs 78.38%, P < 0.05). For the HBeAg-negative CHB patients, no significant difference was found between Groups A and B at week 192 in terms of reductions in HBV DNA levels from baseline (6.05 Log10 IU/mL vs 6.03 Log10 IU/mL, P > 0.05), percentages of patients who achieved undetectable HBV DNA (100% vs 100%, P > 0.05) and rates of ALT normalization (95.65% vs 100.00%, P > 0.05). Safety and adverse event profiles were similar between Groups A and B. Two HBeAg-positive patients in Group A and 5 in Group B developed genotypic resistance to ETV. CONCLUSION Long-term ETV maleate treatment for up to 192 wk is effective and safe in Chinese CHB patients predominantly genotyped as B or C.
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Affiliation(s)
- Jing-Hang Xu
- Department of Infectious Diseases, Center for Liver Diseases, Peking University First Hospital, Beijing 100094, China
| | - Sa Wang
- Clinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Da-Zhi Zhang
- Department of Infectious Diseases, The Second Affiliated Hospital with Chongqing Medical University, Chongqing 400010, China
| | - Yan-Yan Yu
- Department of Infectious Diseases, Center for Liver Diseases, Peking University First Hospital, Beijing 100094, China
| | - Chong-Wen Si
- Department of Infectious Diseases, Center for Liver Diseases, Peking University First Hospital, Beijing 100094, China
| | - Zheng Zeng
- Department of Infectious Diseases, Center for Liver Diseases, Peking University First Hospital, Beijing 100094, China
| | - Zhong-Nan Xu
- Jiangsu Chia-tai Tianqing Pharmaceutical Co., Ltd, Nanjing 222006, Jiangsu Province, China
| | - Jun Li
- Department of Infectious Diseases, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Qing Mao
- Department of Infectious Diseases, Southwest China Hospital, Chongqing 400038, China
| | - Hong Tang
- Department of Infectious Diseases, West China Hospital, Chengdu 610041, Sichuan Province, China
| | - Ji-Fang Sheng
- Department of Infectious Diseases, The First Affiliated Hospital of Zhejiang University, Hangzhou 310010, Zhejiang Province, China
| | - Xin-Yue Chen
- Department of International Medicine, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
| | - Qin Ning
- Department and Institute of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Guang-Feng Shi
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Jiaotong University School of Medicine, Shanghai 200025, China
| | - Xi-Quan Zhang
- Jiangsu Chia-tai Tianqing Pharmaceutical Co., Ltd, Nanjing 222006, Jiangsu Province, China
| | - Jun Dai
- Jiangsu Chia-tai Tianqing Pharmaceutical Co., Ltd, Nanjing 222006, Jiangsu Province, China
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Xu J, Fan Y, Yu Y, Si C, Zeng Z, Xu Z, Li J, Mao Q, Zhang D, Tang H, Sheng J, Chen X, Ning Q, Shi G, Xie Q, Zhang X, Dai J. 240-week entecavir maleate treatment in Chinese chronic hepatitis B predominantly genotype B or C. J Viral Hepat 2022; 29:862-867. [PMID: 35737855 PMCID: PMC9545224 DOI: 10.1111/jvh.13724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Accepted: 04/25/2022] [Indexed: 02/05/2023]
Abstract
This study aimed to evaluate the efficacy and safety of entecavir(ETV) versus ETV maleate in Chinese patients with chronic hepatitis B(CHB). This was a randomized, double-blind, double-dummy, controlled, multicentre study. Patients were randomly assigned to receive 48 weeks of treatment with 0.5 mg/day ETV (group A) or 0.5 mg/day ETV maleate (group B), then, all patients received treatment with 0.5 mg/day ETV maleate from week 49 onwards. Patients were regularly followed up. Serum hepatitis B virus (HBV) markers were detected. Adverse events (AE) were recorded. The primary endpoint was the decline in HBV DNA in each group at the end of treatment. Secondary endpoints included the rate of HBV DNA below the lower limit of detection (LLOD) (20 I U/ml) at the end of treatment, the rate of hepatitis B e antigen (HBeAg) loss, the rate of HBeAg seroconversion and serum alanine aminotransferase (ALT) normalization. One hundred and thirty-seven (71 in group A) patients with HBeAg-positive CHB and 46 (21 in group A) patients with HBeAg-negative CHB completed the 240-week treatment and follow-up. Baseline characteristics were well balanced between the two groups. For the HBeAg-positive CHB patients, the mean HBV DNA level had similarly decreased from baseline in both groups (A: by 6.67 log10 IU/ml vs. B: by 6.74 log10 IU/ml; p > .05) at Week 240. Patients who achieved undetectable levels of serum HBV DNA (<20 IU/ml) at Week 240 were similar between groups (A:91.55% vs. B:87.88%; p > .05). Both groups achieved similar HBeAg seroconversion rates at week 240 (A:26.98% vs. B:20.97%; p > .05). Both groups achieved similar normalization of ALT (A:87.32% vs. B:83.61%; p > .05) at Week 240 (p > .05). For the HBeAg-negative CHB patients, the mean HBV DNA level had similarly decreased from baseline in both groups (A: by 6.05 log10 IU/ml vs. B: by 6.10 log10 IU/ml; p > .05) at Week 240. Patients who achieved undetectable levels of serum HBV DNA at Week 240 were similar between groups (A:100% vs. B:100%). Both groups achieved similar normalization rates (A:90.91% vs. B: 95.45%; p > .05) of ALT at Week 240 (p > .05). In conclusion, long-term ETV maleate treatment was safe and efficient in Chinese CHB predominantly of genotype B or C.
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Affiliation(s)
- Jing‐Hang Xu
- Department of Infectious Diseases, Center for Liver DiseasesPeking University First HospitalBeijingChina
| | - Ya‐Nan Fan
- Department of Infectious Diseases, Center for Liver DiseasesPeking University First HospitalBeijingChina
| | - Yan‐Yan Yu
- Department of Infectious Diseases, Center for Liver DiseasesPeking University First HospitalBeijingChina
| | - Chong‐Wen Si
- Department of Infectious Diseases, Center for Liver DiseasesPeking University First HospitalBeijingChina
| | - Zheng Zeng
- Department of Infectious Diseases, Center for Liver DiseasesPeking University First HospitalBeijingChina
| | - Zhong‐Nan Xu
- Jiangsu Chia‐tai Tianqing Pharmaceutical Co, LtdNanjingChina
| | - Jun Li
- Department of Infectious DiseasesThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
| | - Qing Mao
- Department of Infectious DiseasesSouthwest China HospitalChongqingChina
| | - Da‐Zhi Zhang
- Department of Infectious DiseasesThe Second Affiliated Hospital of Chongqing Medical UniversityChongqingChina
| | - Hong Tang
- Department of Infectious DiseasesWest China HospitalChengduChina
| | - Ji‐Fang Sheng
- Department of Infectious DiseasesThe First Affiliated Hospital of Zhejiang UniversityHangzhouChina
| | - Xin‐Yue Chen
- Department of International Medicine, Beijing Youan HospitalCapital Medical UniversityBeijingChina
| | - Qin Ning
- Department and Institute of Infectious Diseases, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Guang‐Feng Shi
- Department of Infectious Diseases, Huashan HospitalFudan UniversityShanghaiChina
| | - Qing Xie
- Department of Infectious Diseases, Ruijin HospitalJiaotong University School of MedicineShanghaiChina
| | - Xi‐Quan Zhang
- Jiangsu Chia‐tai Tianqing Pharmaceutical Co, LtdNanjingChina
| | - Jun Dai
- Jiangsu Chia‐tai Tianqing Pharmaceutical Co, LtdNanjingChina
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