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Li J, Ma X, Xuan Q, Li Q, Wu M, Shi B, Fang Z, Chen L, Chen J, Wen Y, Zhu C, Zhu L, Zhang X, Yuan Z. Modulation of monocyte activity by hepatocellular MicroRNA delivery through HBsAg particles: Implications for pathobiology of chronic hepatitis B. Hepatology 2025; 81:990-1005. [PMID: 38904485 PMCID: PMC11825484 DOI: 10.1097/hep.0000000000000972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Accepted: 05/21/2024] [Indexed: 06/22/2024]
Abstract
BACKGROUND AND AIMS HBsAg serves as an important immune-modulatory factor in chronic hepatitis B. One aspect of such modulation may act through monocytes, which are the major Ag-presenting cells taking up HBsAg. There is evidence for the encapsulation of hepatocellular microRNAs (miRNAs) by HBsAg particles, while its pathobiological significance is unclear. Here, we characterized the miRNA profile in patients with chronic hepatitis B and probed their association with liver inflammation. APPROACHES AND RESULTS We collected plasma from patients that are treatment-naive with chronic hepatitis B (n = 110) and quantified total/HBsAg-enveloped miRNAs by qRT-PCR and plasma cytokines by ELISA. The biological effects of HBsAg-delivered miRNAs in monocytes were evaluated using multiple approaches. The clinical significance of candidate miRNAs and cytokines was corroborated in patients with HBV-associated advanced liver diseases. The plasma miRNA profile showed 2 major clusters, one significantly associated with HBsAg titer and the other correlated with liver inflammation. Among HBsAg-carried miRNAs, miR-939 displayed the most significant correlation with IL-8. Mechanistically, miR-939 in subviral particles enters monocytes and significantly augments IL-8 production through the mitogen-activated protein kinase (MAPK) p38 signaling pathway. Finally, the findings that miR-939 positively correlated with IL-8 level and inflammation/fibrosis stage in the cohort of HBV-associated advanced liver diseases support its causative role in the progression of liver diseases. CONCLUSIONS HBsAg particles carry hepatocellular miRNAs, including miR-939, which enter monocytes and alter their functional status, such as IL-8 secretion. Our findings demonstrate that the HBsAg-miR-939-IL-8 axis may play a crucial role in HBV-induced hepatic necro-inflammation and the progression of advanced liver diseases.
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Affiliation(s)
- Jin Li
- Key Laboratory of Medical Molecular Virology (MOE/NHC), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College Fudan University, Shanghai, China
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Xiao Ma
- Key Laboratory of Medical Molecular Virology (MOE/NHC), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College Fudan University, Shanghai, China
- Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Qinkao Xuan
- Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Qiang Li
- Research Unit, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Min Wu
- Research Unit, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Bisheng Shi
- Department of Laboratory Medicine, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China
| | - Zhong Fang
- Key Laboratory of Medical Molecular Virology (MOE/NHC), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College Fudan University, Shanghai, China
| | - Liang Chen
- Research Unit, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Jieliang Chen
- Key Laboratory of Medical Molecular Virology (MOE/NHC), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College Fudan University, Shanghai, China
| | - Yumei Wen
- Key Laboratory of Medical Molecular Virology (MOE/NHC), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College Fudan University, Shanghai, China
| | - Chuanwu Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Li Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Xiaonan Zhang
- Research Unit, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
- Department of Biomedical Sciences, Faculty of Science and Technology, University of Canberra, Australia
| | - Zhenghong Yuan
- Key Laboratory of Medical Molecular Virology (MOE/NHC), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College Fudan University, Shanghai, China
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Jiang C, Zhang ZH, Li JX. Current status of drug therapy for chronic hepatitis B. World J Gastroenterol 2025; 31:99443. [PMID: 39811512 PMCID: PMC11684199 DOI: 10.3748/wjg.v31.i2.99443] [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: 07/22/2024] [Revised: 11/04/2024] [Accepted: 11/25/2024] [Indexed: 12/18/2024] Open
Abstract
In this editorial, we comment on the article by Meng et al. Chronic hepatitis B (CHB) is a significant global health problem, particularly in developing countries. Hepatitis B virus (HBV) infection is one of the most important risk factors for cirrhosis and hepatocellular carcinoma. Prevention and treatment of HBV are key measures to reduce complications. At present, drug therapy can effectively control virus replication and slow disease progression, but completely eliminating the virus remains a challenge. Anti-HBV treatment is a long-term process, and there are many kinds of antiviral drugs with different mechanisms of action, it is essential to evaluate the safety and efficacy of these drugs to reduce side effects and improve patients' compliance. We will summarize the current status of CHB drug treatment, hoping to provide a reference for the selection of clinical antiviral drugs.
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Affiliation(s)
- Chuang Jiang
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Zhi-Hong Zhang
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jia-Xin Li
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
- Department of General Surgery, Dafang County People's Hospital, Bijie 551600, Guizhou Province, 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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Liu Y, Wu D, Zhang K, Ren R, Liu Y, Zhang S, Zhang X, Cheng J, Chen L, Huang J. Detection technology and clinical applications of serum viral products of hepatitis B virus infection. Front Cell Infect Microbiol 2024; 14:1402001. [PMID: 39035352 PMCID: PMC11257880 DOI: 10.3389/fcimb.2024.1402001] [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: 03/16/2024] [Accepted: 06/12/2024] [Indexed: 07/23/2024] Open
Abstract
Viral hepatitis, caused by its etiology, hepatitis virus, is a public health problem globally. Among all infections caused by hepatitis-associated viruses, hepatitis B virus (HBV) infection remains the most serious medical concern. HBV infection particularly affects people in East Asia and Africa, the Mediterranean region, and Eastern Europe, with a prevalence rate of > 2%. Currently, approximately 1 billion people worldwide are infected with HBV, and nearly 30% of them experience chronic infection. Chronic HBV infection can lead to chronic hepatitis B (CHB), liver cirrhosis, and hepatocellular carcinoma (HCC), resulting in the related death of approximately 1 million people annually. Although preventative vaccines and antiviral therapies are currently available, there is no cure for this infection. Clinical testing is not only the gateway for diagnosis of HBV infection, but also crucial for judging the timing of medication, evaluating the effect of antiviral therapy, and predicting the risk of relapse after drug withdrawal in the whole follow-up management of hepatitis B infected persons. With advances in detection technology, it is now possible to measure various viral components in the blood to assess the clinical status of HBV infection. Serum viral products of HBV infection, such as HBV DNA, HBV RNA, hepatitis B surface antigen, hepatitis B e-antigen, and hepatitis B core-related antigen, are non-invasive indicators that are critical for the rapid diagnosis and management of related diseases. Improving the sensitivity of monitoring of these products is essential, and the development of corresponding detection technologies is pivotal in achieving this goal. This review aims to offer valuable insights into CHB infection and references for its effective treatment. We provide a comprehensive and systematic overview of classical and novel methods for detecting HBV serum viral products and discusses their clinical applications, along with the latest research progress in this field.
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Affiliation(s)
- Ying Liu
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Di Wu
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Kui Zhang
- State Key Laboratory of Resource Insects, College of Sericulture, Textile and Biomass Sciences, Southwest University, Chongqing, China
| | - Rongrong Ren
- Department of Clinical Laboratory, Zhejiang Hospital, Hangzhou, Zhejiang, China
| | - Yuxuan Liu
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Shuya Zhang
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Xuanyu Zhang
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Jilin Cheng
- Department of Gastroenterology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Liping Chen
- Department of Gastroenterology, Shanghai Geriatric Medical Center, Shanghai, China
| | - Jun Huang
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
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Lai X, OuYang W, Li S, Qiu J, Zhang H, Jiang T, Qin X, Tang L, Gu Y, Yao Z, Peng S. Predictive role of early treatment dynamics of HBV RNA and HBcrAg for HBeAg seroconversion in children with chronic hepatitis B. J Med Virol 2024; 96:e29670. [PMID: 38773810 DOI: 10.1002/jmv.29670] [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: 11/26/2023] [Revised: 04/27/2024] [Accepted: 05/05/2024] [Indexed: 05/24/2024]
Abstract
This study aimed to assess the predictive capacity of emerging serological markers, serum HBV RNA and HBcrAg, for HBeAg seroconversion in children with HBeAg-positive chronic hepatitis B (CHB). Treatment-naïve HBeAg-positive CHB children who admitted to the Liver Disease Center of Hunan Children's Hospital between April 2021 and September 2022 and received treatment with the combined entecavir and interferon-alpha treatment were recruited. Serum HBV RNA and HBcrAg were measured at baseline and Weeks 12, 24, and 48 of treatment. Our study showed that serum HBV RNA (HR = 0.71, 95% CI: 0.56-0.91, p = 0.006), HBcrAg (HR = 0.60, 95% CI: 0.43-0.84, p = 0.003), and HBsAg (HR = 0.49, 95%CI: 0.36-0.69, p < 0.001) at Week 12 were independent predictors of HBeAg seroconversion. ROC curve analysis presented that serum HBV RNA decline value (ΔHBV RNA) at Week 36 and HBcrAg decline value (ΔHBcrAg) at Week 12 (AUC = 0.871, p = 0.003 and AUC = 0.810, p = 0.003, respectively) could effectively predict HBeAg seroconversion. Furthermore, the optimal critical values were determined and the children with ΔHBV RNA > 3.759 log10 copies/mL at Week 36 or ΔHBcrAg >0.350 log10 U/mL at Week 12 more likely to achieve HBeAg seroconversion. The serum HBV RNA and HBcrAg provide new insights into the treatment of CHB in children. Early assessment of serum HBV RNA and HBcrAg during treatment can assist clinical decision-making and optimize individualized therapeutic approaches.
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Affiliation(s)
- Xin Lai
- Department of Maternal and Child Health, Xiangya School of Public Health, Central South University, Changsha, China
- The Affiliated Women and Children's Hospital of Xiamen University, Xiamen, China
| | - Wenxian OuYang
- Liver Disease Center, Hunan Children's Hospital, Changsha, China
| | - Shuangjie Li
- Liver Disease Center, Hunan Children's Hospital, Changsha, China
| | - Jun Qiu
- Liver Disease Center, Hunan Children's Hospital, Changsha, China
| | - Hui Zhang
- Liver Disease Center, Hunan Children's Hospital, Changsha, China
| | - Tao Jiang
- Liver Disease Center, Hunan Children's Hospital, Changsha, China
| | - Xiaomei Qin
- Liver Disease Center, Hunan Children's Hospital, Changsha, China
| | - Lian Tang
- Liver Disease Center, Hunan Children's Hospital, Changsha, China
| | - Yingping Gu
- Department of Maternal and Child Health, Xiangya School of Public Health, Central South University, Changsha, China
| | - Zhenzhen Yao
- Department of Maternal and Child Health, Xiangya School of Public Health, Central South University, Changsha, China
| | - Songxu Peng
- Department of Maternal and Child Health, Xiangya School of Public Health, Central South University, Changsha, China
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Zheng F, Tan Z, Liang Z, Xiang W. Efficacy and Safety of Antiviral Therapy for Immune-tolerant Hepatitis B Viral Infection in Children: A Systematic Review and Meta-analysis. Pediatr Infect Dis J 2023; 42:942-948. [PMID: 37523508 DOI: 10.1097/inf.0000000000004057] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/02/2023]
Abstract
BACKGROUND Chronic hepatitis B virus (HBV) infection burden in children remains a pressing public health concern. Whether antiviral therapy should be administered to children with HBV in the immune-tolerant phase remains controversial. We performed a meta-analysis to evaluate antiviral therapy efficacy and safety in children with immune-tolerant hepatitis B (ITHB). METHODS A search was conducted in multiple databases (PubMed, Embase, Cochrane, Web of Science, CBM, CNKI and Wanfang Data) to identify clinical trials examining antiviral therapy efficacy and safety in children (1-18 years) with ITHB viral infection from inception to February 2023. Outcomes were calculated separately for controlled and single-arm studies. RESULTS Nine trials (442 patients), including 2 randomized controlled trials (RCTs), 3 non-RCTs and 4 single-arm studies, were included in this meta-analysis. In the RCTs, antiviral therapy group exhibited greater rates of HBsAg loss [risk ratio (RR) = 6.11, 95% confidence interval (CI): 1.67-22.31, P Z-test = 0.006], HBsAg serologic response (RR = 5.29, 95% CI: 1.47-19.07, P Z-test = 0.011) and HBeAg loss (RR = 3.00, 95% CI: 1.35-6.66, P Z-test = 0.007) compared with the control group at the end of follow-up. In single-arm studies, the pooled incidences of HBsAg loss, HBeAg loss and HBsAg seroconversion were 24% (95% CI: -0.1% to 48%), 24% (95% CI: -0.1% to 48%) and 24% (95% CI: -5% to 52%), respectively. CONCLUSION Current evidence suggests the effectiveness of antiviral therapy in children with HBV infection in the immune-tolerant stage, with few serious adverse events. Due to the limited quality and number of included studies, more high-quality studies are required to validate our findings.
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Affiliation(s)
- Fengli Zheng
- From the Department of Pediatrics, The People's Hospital of Guigang, Guigang, Guangxi, China
| | - Zhijun Tan
- Department of Infectious Diseases, The People's Hospital of Guigang, Guigang, Guangxi, China
| | - Zhou Liang
- Department of Infectious Diseases, The People's Hospital of Guigang, Guigang, Guangxi, China
| | - Wenyao Xiang
- Department of Infectious Diseases, The People's Hospital of Guigang, Guigang, Guangxi, China
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Li J, Han KX, Shen JP, Sun WJ, Gao L, Gao YF. Value of XGBoost machine learning model for diagnosis of hepatitis B cirrhosis. Shijie Huaren Xiaohua Zazhi 2023; 31:544-554. [DOI: 10.11569/wcjd.v31.i13.544] [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: 04/19/2023] [Revised: 05/25/2023] [Accepted: 06/21/2023] [Indexed: 07/08/2023] Open
Abstract
BACKGROUND The progression of chronic hepatitis B into cirrhosis is slow and easily ignored, and the construction of a noninvasive diagnostic model for cirrhosis based on routine clinical indicators has become a hot research topic. However, there is still a lack of machine learning models regarding the early diagnosis of cirrhosis.
AIM To investigate the performance of the extreme gradient boosting (XGBoost) machine model in the diagnosis of hepatitis B cirrhosis.
METHODS A retrospective analysis was performed on 1087 patients with chronic hepatitis B virus infection (CHBV) diagnosed for the first time at the Department of Infection, The First/Second Affiliated Hospital of Anhui Medical University from 2010 to 2018. The patients were divided into training and validation sets in a 3:1 ratio according to the randomization principle. Clinical data of all study participants were collected and prediction models were constructed using XGBoost machine learning model. Meanwhile, the aspartate aminotransferase/platelet ratio index (APRI) and fibrosis-4 index (FIB-4) scores were calculated and compared with the XGBoost machine learning model. Area under the curve (AUC) was used to assess the model discrimination, and calibration curve (CA) and decision curve analysis (DCA) were used to assess the model calibration and benefit.
RESULTS A total of 1087 CHBV patients were included, including 817 in the training set and 270 in the validation set. There was no statistical difference between the training and validation sets for all predictor variables (P > 0.05). Cirrhosis occurred in 103 patients in the training set, and APRI and FIB-4 scores were significantly higher in cirrhotic patients than in non-cirrhotic patients (P < 0.05). The relative importance of platelets was the highest among all predictors. The AUCs of the model in the training and validation sets were 0.95 and 0.86 (P < 0.05), respectively, and the Kappa values were 0.78 and 0.74, which suggested that the model was reproducible. CA curve analysis indicated that the model predicted a high degree of agreement with the true situation fit. DCA of the training and validation sets implied that the developed model could result in a high degree of benefit for patients. XGBoost machine learning model was significantly more efficient for the diagnosis of cirrhosis than APRI and FIB-4 scores.
CONCLUSION The XGBoost machine learning model constructed in this study based on common clinical information of CHBV patients has an excellent performance for the diagnosis of cirrhosis and deserves further clinical promotion.
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Affiliation(s)
- Ji Li
- Department of Infection, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui Province, China
| | - Ke-Xing Han
- Department of Infection, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui Province, China
| | - Jia-Pei Shen
- Department of Infection, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui Province, China
| | - Wei-Jie Sun
- Department of Infection, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui Province, China
| | - Long Gao
- Department of Infection, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui Province, China
| | - Yu-Feng Gao
- Department of Infection, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui Province, China
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Raihan R, Akbar SMF. A Narrative Review on the Specific Pattern of HBV Genotype in Bangladesh: Clinical Implications for Management. Euroasian J Hepatogastroenterol 2023; 13:152-158. [PMID: 38222956 PMCID: PMC10785131 DOI: 10.5005/jp-journals-10018-1412] [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: 10/19/2023] [Accepted: 11/21/2023] [Indexed: 01/16/2024] Open
Abstract
Background and aims Bangladesh's unique epidemiological landscape presents an intriguing puzzle. This South Asian nation, with its complex sociodemographic and environmental factors, is home to a diverse array of hepatitis-B virus (HBV) genotypes, identified as Genotype C, with Genotypes D and A also making a significant contribution to the viral landscape. Reviewing such insights is necessary not only to underscore the country's regional diversity in HBV strains but also to bring into focus the clinical implications these genetic variations may have on disease progression and management. Methods A thorough database search covered various sources using relevant keywords like "Hepatitis B virus genotypes", "HBV genotypes in Bangladesh", and "HBV clinical implications". The review synthesized findings and analyzed HBV genotype prevalence and clinical implications in Bangladesh. Results Genotypes C and D collectively represent 82% of chronic hepatitis-B infection (CHB) cases in Bangladesh, underscoring their regional prevalence. The geographic context is pivotal in understanding HBV infection dynamics and disease progression in this area. Notably, genotype C and the presence of A1762T/G1764A mutations appear to have a distinct impact on disease development, potentially affecting the immune response in CHB patients. This highlights the need for tailored management approaches in this specific region. Further research is vital to confirm and elaborate on these findings, particularly in relation to how these mutations influence the host's immune response. Conclusion and clinical significance In summary, studies on HBV genotypes in Bangladesh stress the need for genotype-specific clinical considerations and more research to improve diagnostics and therapies. How to cite this article Raihan R, Akbar SMF. A Narrative Review on the Specific Pattern of HBV Genotype in Bangladesh: Clinical Implications for Management. Euroasian J Hepato-Gastroenterol 2023;13(2):152-158.
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Affiliation(s)
- Ruksana Raihan
- Department of Microbiology, US Bangla Medical College and Hospital, University of Malaya, Dhaka, Bangladesh
| | - Sheikh Mohammad Fazle Akbar
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine; Research Center for Global and Local Infectious Diseases, Faculty of Medicine, Oita University, Oita; Miyakawa Memorial Research Foundation, Tokyo, Japan
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Dumolard L, Aspord C, Marche PN, Macek Jilkova Z. Immune checkpoints on T and NK cells in the context of HBV infection: Landscape, pathophysiology and therapeutic exploitation. Front Immunol 2023; 14:1148111. [PMID: 37056774 PMCID: PMC10086248 DOI: 10.3389/fimmu.2023.1148111] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 03/10/2023] [Indexed: 03/30/2023] Open
Abstract
In hepatitis B virus (HBV) infection, the interplay between the virus and the host immune system is crucial in determining the pathogenesis of the disease. Patients who fail to mount a sufficient and sustained anti-viral immune response develop chronic hepatitis B (CHB). T cells and natural killer (NK) cells play decisive role in viral clearance, but they are defective in chronic HBV infection. The activation of immune cells is tightly controlled by a combination of activating and inhibitory receptors, called immune checkpoints (ICs), allowing the maintenance of immune homeostasis. Chronic exposure to viral antigens and the subsequent dysregulation of ICs actively contribute to the exhaustion of effector cells and viral persistence. The present review aims to summarize the function of various ICs and their expression in T lymphocytes and NK cells in the course of HBV infection as well as the use of immunotherapeutic strategies targeting ICs in chronic HBV infection.
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Affiliation(s)
- Lucile Dumolard
- University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Team Epigenetics, Immunity, Metabolism, Cell Signaling & Cancer, Institute for Advanced Biosciences, Grenoble, France
| | - Caroline Aspord
- University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Team Epigenetics, Immunity, Metabolism, Cell Signaling & Cancer, Institute for Advanced Biosciences, Grenoble, France
- R&D Laboratory, Etablissement Français du Sang Auvergne-Rhone-Alpes, Grenoble, France
| | - Patrice N. Marche
- University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Team Epigenetics, Immunity, Metabolism, Cell Signaling & Cancer, Institute for Advanced Biosciences, Grenoble, France
| | - Zuzana Macek Jilkova
- University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Team Epigenetics, Immunity, Metabolism, Cell Signaling & Cancer, Institute for Advanced Biosciences, Grenoble, France
- Hepato-Gastroenterology and Digestive Oncology Department, CHU Grenoble Alpes, Grenoble, France
- *Correspondence: Zuzana Macek Jilkova,
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Wang J, Yan X, Zhu L, Liu J, Qiu Y, Li Y, Liu Y, Xue R, Zhan J, Jiang S, Geng Y, Wan Y, Li M, Mao M, Gao D, Yin S, Tong X, Xia J, Ding W, Chen Y, Li J, Zhu C, Huang R, Wu C. Significant histological disease of patients with chronic hepatitis B virus infection in the grey zone. Aliment Pharmacol Ther 2023; 57:464-474. [PMID: 36324235 DOI: 10.1111/apt.17272] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 08/08/2022] [Accepted: 10/15/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND Many patients with chronic hepatitis B (CHB) do not meet the definitions of the traditional natural phases and are classified as being in the grey zone (GZ). AIMS To investigate liver histology, and to establish a management strategy for patients with CHB in the GZ. METHODS This study included 1043 patients with CHB who underwent liver biopsy. Phases of natural history were determined according to the AASLD 2018 hepatitis B guidance. CHB patients in the GZ were divided into HBeAg-positive, normal ALT and HBV DNA ≤106 IU/ml (GZ-A); HBeAg-positive, elevated ALT and HBV DNA ≤2 × 104 IU/ml (GZ-B); HBeAg-negative, normal ALT and HBV DNA ≥2 × 103 IU/ml (GZ-C) and HBeAg-negative, elevated ALT and HBV DNA ≤2 × 103 IU/ml (GZ-D). Significant histological disease was defined as liver inflammation ≥G2 and/or liver fibrosis ≥S2. RESULTS Two hundred and forty two (23.2%) patients were in the GZ. Approximately 72.7% had significant histological disease. HBeAg-positive GZ CHB patients had a higher proportion of significant histological disease than HBeAg-negative GZ patients (91.1% vs. 68.5%, p = 0.002). GZ-D (42.6%) was the dominant category, followed by GZ-C (38.8%), GZ-A (10.3%) and GZ-B (8.3%). The highest proportion of significant histological disease was observed patients in GZ-B (100.0%), followed by GZ-A (84.0%), GZ-D (69.9%) and GZ-C (67.0%). Prothrombin time (PT) was an independent risk factor of significant histological disease in the HBeAg-negative GZ. CONCLUSIONS Over 70% of GZ CHB patients had significant histological disease. We recommend antiviral treatment for HBeAg-positive and HBeAg-negative GZ CHB patients with high PT.
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Affiliation(s)
- Jian Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Xiaomin Yan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Li Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Jiacheng Liu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.,Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Yuanwang Qiu
- Department of Infectious Diseases, The Fifth People's Hospital of Wuxi, Wuxi, Jiangsu, China
| | - Yiguang Li
- Department of Infectious Diseases, The Fifth People's Hospital of Wuxi, Wuxi, Jiangsu, China
| | - Yilin Liu
- 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
| | - Jie Zhan
- 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
| | - Yu Geng
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Yawen Wan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Xuzhou Medical University, Nanjing, Jiangsu, China
| | - Ming Li
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Minxin Mao
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Dongmei Gao
- Department of Hepatology, Huai'an No. 4 People's Hospital, Huai'an, Jiangsu, China
| | - Shengxia Yin
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Xin Tong
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Juan Xia
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Weimao Ding
- Department of Hepatology, Huai'an No. 4 People's Hospital, Huai'an, Jiangsu, China
| | - Yuxin Chen
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China.,Department of Laboratory Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Jie Li
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Chuanwu Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Rui Huang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 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, The Affiliated Hospital of Nanjing University Medical School, 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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Behzadi A, imani S, Deravi N, Mohammad Taheri Z, mohammadian F, moraveji Z, Shavysi S, Mostafaloo M, Soleimani Hadidi F, Nanbakhsh S, Olangian-Tehrani S, Marabi MH, behshood P, Poudineh M, Kheirandish A, Keylani K, Behfarnia P. Antiviral Potential of Melissa officinalis L.: A Literature Review. Nutr Metab Insights 2023; 16:11786388221146683. [PMID: 36655201 PMCID: PMC9841880 DOI: 10.1177/11786388221146683] [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: 04/13/2022] [Accepted: 12/05/2022] [Indexed: 01/13/2023] Open
Abstract
The use of synthetic drugs has increased in recent years; however, herbal medicine is yet more trusted among a huge population worldwide; This could be due to minimal side effects, affordable prices, and traditional beliefs. Lemongrass (Melissa officinalis) has been widely used for reducing stress and anxiety, increasing appetite and sleep, reducing pain, healing wounds, and treating poisonous insect bites and bee stings for a long time. Today, research has shown that this plant can also fight viruses including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Herpes Simplex Virus (HSV), and Human Immunodeficiency Virus (HIV) through various mechanisms such as inhibiting HSV-1 from binding to host cell, inhibiting HSV-1 replication during the post-adsorption or inhibiting main protease and spike protein of SARS-CoV-2, furthermore, be effective in treating related diseases. This Review investigated the antiviral properties of Melissa officinalis and its effect on viral diseases. More in vitro and in vivo studies are needed to determine Melissa officinaliss underlying mechanism, and more randomized controlled trials should be done to identify its effect in humans. Also, due to the usefulness and lack of side effects, it can be used more as a complementary medicine.
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Affiliation(s)
- Amirhossein Behzadi
- School of Medicine, Iran University of Medical Sciences, Tehran, Iran
- Avicennet, Tehran, Iran
| | - Sadegh imani
- Student Research Committee, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Niloofar Deravi
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - fatemeh mohammadian
- Student Research Committee, International Campus, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - zahra moraveji
- Student Research Committee, International Campus, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Sepideh Shavysi
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Motahareh Mostafaloo
- School of Nursing and Midwifery, Iran University of Medical Science, Tehran, Iran
| | - Fateme Soleimani Hadidi
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sepehr Nanbakhsh
- School of Medicine, Iran University of Medical Sciences, Tehran, Iran
- Avicennet, Tehran, Iran
| | - Sepehr Olangian-Tehrani
- School of Medicine, Iran University of Medical Sciences, Tehran, Iran
- Avicennet, Tehran, Iran
| | - Mohammad Hesam Marabi
- Student Research Committee, School of Dentistry, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Parisa behshood
- Department of Microbiology, Young Researchers and Elite Club, Shahrekord Branch, Islamic Azad University, Isfahan, Iran
| | | | - Ali Kheirandish
- Student Research Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
| | - Kimia Keylani
- School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Pooya Behfarnia
- School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
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12
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Taye BW, Valery PC, Clark PJ. Targeted antiviral treatment of hepatitis B virus in culturally and linguistically diverse populations to achieve elimination targets in Australia. J Viral Hepat 2022; 29:868-878. [PMID: 35748684 PMCID: PMC9544141 DOI: 10.1111/jvh.13727] [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: 04/14/2022] [Revised: 06/03/2022] [Accepted: 06/09/2022] [Indexed: 12/09/2022]
Abstract
The majority of Australia's hepatitis B virus (HBV) burden is borne by culturally and linguistically diverse (CALD) populations, and antiviral treatment is the mainstay of intervention. Using modelling, we estimated the impact of targeted antiviral treatment scale-up and changes in migration on HBV-related mortality and HBV elimination in CALD populations in Australia. We fitted a deterministic mathematical model based on the natural history of HBV and the Australian migration effect in four CALD population groups according to country of birth. We used three antiviral treatment scale-up scenarios: baseline (9.3% coverage); intermediate (coverage of 80% of patients eligible for antiviral therapy by 2030); and optimistic (coverage of 20% of all patients living with HBV by 2022). Our model predicted that if the baseline treatment is followed between 2015 and 2030, the number of chronic HBV cases and HBV-related mortality will increase. Following the optimistic scale-up, the number of new HBV cases could be reduced by 78%, 73%, 74% and 83% in people born in Asia-Pacific, Europe, Africa and the Middle East, and Americas, respectively, between 2015 and 2030. An optimistic treatment scale-up could result in a 19.2%-24.5% reduction in HBV-related mortality and a 15%-25% reduction in HCC-related mortality in CALD populations between 2015 and 2030. In conclusion, our findings highlight that targeted antiviral treatment for CALD populations provides significant health system benefits by reducing HBV-related complications from cirrhosis and HCC. Expanded antiviral treatment programmes focusing on high-prevalence CALD populations may be an effective strategy to reduce HBV-related morbidity and mortality.
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Affiliation(s)
- Belaynew W. Taye
- Faculty of MedicineThe University of QueenslandBrisbaneQueenslandAustralia,Mater Research Institute‐University of QueenslandBrisbaneQueenslandAustralia,Population HealthQIMR Berghofer Medical Research InstituteBrisbaneQueenslandAustralia,Department of EpidemiologyBahir Dar UniversityBahir DarEthiopia
| | - Patricia C. Valery
- Faculty of MedicineThe University of QueenslandBrisbaneQueenslandAustralia,Population HealthQIMR Berghofer Medical Research InstituteBrisbaneQueenslandAustralia
| | - Paul J. Clark
- Faculty of MedicineThe University of QueenslandBrisbaneQueenslandAustralia,Mater Research Institute‐University of QueenslandBrisbaneQueenslandAustralia,Population HealthQIMR Berghofer Medical Research InstituteBrisbaneQueenslandAustralia,Department of Gastroenterology and HepatologyMater HospitalsBrisbaneQueenslandAustralia,Department of Gastroenterology and HepatologyPrincess Alexandra HospitalBrisbaneQueenslandAustralia
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13
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Host Factors in the Natural History of Chronic Hepatitis B: Role of Genetic Determinants. Int J Hepatol 2022; 2022:6046677. [PMID: 36052277 PMCID: PMC9427277 DOI: 10.1155/2022/6046677] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 07/27/2022] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND The host immune system plays an important role in hepatitis B virus (HBV) infection manifestation. Genetic polymorphisms of several inflammatory cytokines, including TNF-α and IL-10, have been associated with chronic hepatitis B (CHB) progression, although with contradicting results. CHB progression can be categorized into four phases, immune tolerance (IT), immune clearance (IC), low/no replicative (LR), and e-negative hepatitis (ENH), with HBeAg seroconversion as an important milestone. Here, we determined the association of TNF-α (rs1800629) and IL-10 (rs1800896 and rs1800872) SNPs in the context of CHB natural history progression, particularly to HBeAg seroconversion, in Indonesian CHB patients. METHODS A total of 287 subjects were recruited and categorized into distinct CHB phases based on HBeAg, viral load, and ALT levels. TNF-α and IL-10 SNPs were determined using PCR-RFLP and confirmed with direct sequencing. The association between SNP genotypes with CHB dynamics was determined using logistic regression presented as odds ratio (OR) with 95% CI. RESULTS No significant association was found between IL-10 -592A/C polymorphism and progression of IT and IC to LR, IT and IC to ENH, and LR to ENH phases in all the gene models. IL-10 rs1800896 and TNF-α rs1800629 could not be analyzed using logistic regression. Subjects' age (≥40 years old) was significantly associated with IT and IC to LR (OR: 2.191, 95% CI 1.067-4.578, P = 0.034), IT and IC to ENH (OR: 7.460, 95% CI 3.316-18.310, P < 0.001), and LR to ENH (OR: 5.252, 95% CI 2.010-14.858, P = 0.001). Male gender was associated with LR to ENH (OR: 4.077, 95% CI 1.605-11.023, P = 0.004). CONCLUSIONS Age and male gender were associated with CHB phase progression instead of the TNF-α and IL-10 polymorphisms. It would be beneficial to study not only the effect of host determinants but also the viral factor to understand the mechanisms of CHB phase progression.
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14
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Xu YH, Xue C. Compound Biejia-Ruangan tablet as an adjunctive therapy to entecavir for chronic hepatitis B complicated with hepatic fibrosis: A systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore) 2022; 101:e30020. [PMID: 35960113 PMCID: PMC9371490 DOI: 10.1097/md.0000000000030020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND The compound Biejia-Ruangan tablet (CBRT), as an adjunctive therapy to entecavir, is a potential treatment for hepatic fibrosis (HF) in patients with chronic hepatitis B (HBV). However, the present study yielded inconsistent results. In this systematic review and meta-analysis, we comprehensively investigated the efficacy and safety of CBRT as an adjunctive modality to entecavir for the treatment of HBV infection complicated with HF. METHODS We searched the Cochrane Library, PubMed, Embase, CNKI, VIP, CBM, and Wangfang databases through April 1, 2022, for randomized controlled trials (RCTs) assessing the effect and safety of CBRT as an adjunctive modality to entecavir for HBV complicated with HF. The primary outcomes were biochemical parameters of serum hyaluronic acid, laminin (LN), pretype-III collagen (PC-III), and type IV collagen (IV-C). The secondary outcomes were liver function indices of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBiL) levels, total effect rate, and occurrence rate of adverse events. Two researchers independently conducted study selection, data extraction, and quality assessment. Statistical analysis was performed using the RevMan 5.3 software. RESULTS Eight RCTs involving 747 patients were included. Compared with entecavir monotherapy, CBRT as an adjunctive therapy to entecavir exerted more encouraging effect in serum levels of hyaluronic acid (mean difference [MD] = -28.15; 95% confidence interval [CI]: -43.82 to -12.47; P < .001), LN (MD = -29.46; 95% CI: -50.69 to -8.23; P < .001), PC-III (MD = -11.83; 95% CI: -19.43 to -4.23; P < .001), and IV-C (MD = -19.62; 95% CI: -29.76 to -9.49; P < .001); levels of serum ALT (MD = -16.83; 95% CI: -26.30 to -7.36; P < .001), AST (MD = -20.52; 95% CI: -33.11 to -7.93; P < .001), and TBiL (MD = -7.54; 95% CI: -11.58 to -3.49; P < .001); and total effect rate (odds ratio = 3.53; 95% CI: 1.71-7.29; P < .001). Meta-analysis results also showed that CBRT as an adjunctive therapy to entecavir had a lower occurrence rate of adverse events (odds ratio = 0.54; 95% CI: 0.22-1.34; P < .001) than entecavir alone. CONCLUSION The results of this study showed that CBRT as an adjunctive modality to entecavir may benefit HBV patients complicated with HF. High-quality RCTs are needed to confirm the current findings in the future.
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Affiliation(s)
- Yong-hong Xu
- Department of Gastroenterology, Sunshine Union Hospital, Weifang, China
| | - Chuan Xue
- Department of Gastroenterology, Sunshine Union Hospital, Weifang, China
- * Correspondence: Chuan Xue, MM, Department of Gastroenterology, Sunshine Union Hospital, No. 9000, Yingqian Street, Weifang High-Tech District, Shandong 261000, China (e-mail: )
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15
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Lefeuvre C, Roux M, Blanchard S, Le Guillou-Guillemette H, Boursier J, Lunel-Fabiani F, Jeannin P, Pivert A, Ducancelle A. Analysis of hepatic fibrosis markers in the serum of chronic hepatitis B patients according to basal core promoter/precore mutants. Sci Rep 2022; 12:10261. [PMID: 35715541 PMCID: PMC9205978 DOI: 10.1038/s41598-022-14285-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 06/03/2022] [Indexed: 12/29/2022] Open
Abstract
The A1762T/G1764A double mutant in the basal core promoter (BCP) region of the hepatitis B virus (HBV) is associated with severe hepatic lesions while the G1899A mutation with the double mutant is associated with a significant reduction in the risk of severe fibrosis. This study aims to measure a number of markers in the serum of patients with chronic HBV infection and to assess relationships between these markers and BCP/precore mutants with consideration of the stage of fibrosis. The serum levels of resistin, TGF-β1, MMP-1, TIMP-1, collagen IA1 and PDGF-BB, which are markers that are known to be involved in the process of hepatic fibrosis, were assayed. The serum levels of PDGF-BB and TIMP-1, and the mutation profile were independently associated with advanced fibrosis. A higher level of TIMP-1 was associated with advanced fibrosis regardless of the mutation status, and a higher level of PDGF-BB was associated with nonsevere fibrosis in patients infected with viruses harboring the A1762T/G1764A or A1762T/G1764A/G1899A mutations. Our results suggest an impact of the A1762T/G1764A mutant on the biological pathway related to TGF-β1 and PDGF-BB. In vitro studies are needed to understand the impact of these mutants on the serum secretion of markers involved in fibrosis severity.
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Affiliation(s)
| | - Marine Roux
- Univ Angers, HIFIH, SFR ICAT, F-49000, Angers, France
| | - Simon Blanchard
- Univ Angers, INSERM Unité 892, CNRS Unit 6299, F-49000, Angers, France
| | | | - Jérôme Boursier
- Univ Angers, CHU Angers, HIFIH, SFR ICAT, F-49000, Angers, France
| | | | - Pascale Jeannin
- Univ Angers, INSERM Unité 892, CNRS Unit 6299, F-49000, Angers, France
| | - Adeline Pivert
- Univ Angers, CHU Angers, HIFIH, SFR ICAT, F-49000, Angers, France
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16
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Hepatitis B elimination in children of Slovenian origin born in Slovenia after the introduction of preventive strategies: The results of a national study. Zdr Varst 2022; 61:109-114. [PMID: 35432613 PMCID: PMC8937590 DOI: 10.2478/sjph-2022-0015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 02/18/2022] [Indexed: 11/20/2022] Open
Abstract
Introduction In Slovenia national strategies to prevent hepatitis B virus (HBV) infection in children were introduced in the mid-nineties. The aim of the present study was to analyze the epidemiological characteristics of chronic hepatitis B infection in children in Slovenia after the introduction of mandatory HBV vaccination of children and mandatory screening of pregnant women for HBV surface antigen (HBsAg) with consecutive active and passive immunization of newborns of HBsAg-positive mothers. Methods Children from all regions of Slovenia whose blood samples tested positive for HBsAg at the national reference laboratory for viral hepatitis between January 1997 and December 2010 were included. Demographic, epidemiological and virological data were reviewed retrospectively. Statistical evaluation of the patients’ characteristics was performed and possible trends during the observation period determined. Results Among 52 HBsAg-positive children, there were 22 (42.3%) girls and 30 (57.7%) boys. Among 40 children tested for HBeAg, 17 were positive (42.5%). The most frequent risk factor for acquiring HBV infection was “presence of HBV infection within the family” (24/35; 68.8%). A significant association between the presence of HBeAg and a viral load of >20,000 IU/ml was found (p=0.001). The difference in the proportion of children of Slovenian origin born before 1994 and after was statistically significant (p=0.039). A statistically significant negative linear trend of the number of diagnosed children in the observed period was found (p=0.006). Conclusions Prevention strategies adopted in the mid-nineties have resulted in the elimination of chronic hepatitis B in children of Slovenian origin born in Slovenia.
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17
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Dondeti MF, Abdelkhalek MS, El-Din Elezawy HM, Alsanie WF, Raafat BM, Gamal-Eldeen AM, Talaat RM. Association between interferon-gamma (IFN-γ) gene polymorphisms (+874A/T and +2109A/G), and susceptibility to hepatitis B viral infection (HBV). J Appl Biomed 2022; 20:37-43. [DOI: 10.32725/jab.2022.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Accepted: 12/16/2021] [Indexed: 12/11/2022] Open
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18
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Global sensitivity analysis of a single-cell HBV model for viral dynamics in the liver. Infect Dis Model 2021; 6:1220-1235. [PMID: 34786526 PMCID: PMC8573155 DOI: 10.1016/j.idm.2021.10.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 10/11/2021] [Accepted: 10/14/2021] [Indexed: 12/24/2022] Open
Abstract
The predictive accuracy of mathematical models representing anything ranging from the meteorological to the biological system profoundly depends on the quality of model parameters derived from experimental data. Hence, robust sensitivity analysis (SA) of these critical model parameters aids in sifting the influential from the negligible out of typically vast parameter regimes, thus illuminating key components of the system under study. We here move beyond traditional local sensitivity analysis to the adoption of global SA techniques. Partial rank correlation coefficient (PRCC) based on Latin hypercube sampling is compared with the variance-based Sobol method. We selected for this SA investigation an infection model for the hepatitis-B virus (HBV) that describes infection dynamics and clearance of HBV in the liver [Murray & Goyal, 2015]. The model tracks viral particles such as the tenacious and nearly ineradicable covalently closed circular DNA (cccDNA) embedded in infected nuclei and an HBV protein known as p36. Our application of these SA methods to the HBV model illuminates, especially over time, the quantitative relationships between cccDNA synthesis rate and p36 synthesis and export. Our results reinforce previous observations that the viral protein, p36, is by far the most influential factor for cccDNA replication. Moreover, both methods are capable of finding crucial parameters of the model. Though the Sobol method is independent of model structure (e.g., linearity and monotonicity) and well suited for SA, our results ensure that LHS-PRCC suffices for SA of a non-linear model if it is monotonic.
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19
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Copeland NK, Eller MA, Kim D, Creegan M, Esber A, Eller LA, Semwogerere M, Kibuuka H, Kiweewa F, Crowell TA, Polyak CS, Ake JA. Brief Report: Increased Inflammation and Liver Disease in HIV/HBV-Coinfected Individuals. J Acquir Immune Defic Syndr 2021; 88:310-313. [PMID: 34267057 DOI: 10.1097/qai.0000000000002760] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Accepted: 06/15/2021] [Indexed: 11/26/2022]
Abstract
OBJECTIVE HIV and hepatitis B virus (HBV) coinfection can accelerate morbidity and mortality, especially in sub-Saharan Africa where both infections are common. Although inflammation contributes to disease progression, more information is needed to better understand the pathology. This study compared markers of cirrhosis and inflammation in HIV/HBV-coinfected individuals compared with monoinfected and uninfected patients. SETTING The HIV/HBV-coinfected subjects from the Ugandan arm of the prospective African Cohort Study were selected for evaluation and matched by age and gender with HIV-monoinfected, HBV-monoinfected, and uninfected controls. METHODS Plasma samples were used to quantify markers of immune activation and inflammation. The FIB-4 (a simple index to predict significant liver fibrosis) score was used to estimate liver fibrosis. Demographic and laboratory characteristics were compared across the groups. RESULTS Together, 31 HIV/HBV-coinfected participants were identified and compared with 62 HIV-monoinfected, 7 HBV-monoinfected, and 62 uninfected controls. The HIV/HBV-coinfected group had generally higher levels of inflammation. Most notably, matrix metalloproteinase-2, matrix metalloproteinase-9, and fibroblast growth factor-19 levels were dysregulated among the HIV/HBV-coinfected individuals. Furthermore, the FIB-4 score was higher in the HIV/HBV-coinfected group compared with the HIV-monoinfected group and revealed that 11% of HIV/HBV-coinfected individuals had evidence of undiagnosed advanced liver disease. CONCLUSIONS Differences in levels of inflammation exist between individuals with HIV/HBV coinfection compared with monoinfected and uninfected controls. A distinct signature of inflammation was associated with HIV/HBV coinfection that could reflect the mechanism of liver fibrosis and increased risk for disease progression. Finally, there may be an underappreciated amount of undiagnosed advanced liver disease in sub-Saharan Africa.
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Affiliation(s)
- Nathanial K Copeland
- Kombewa Clinical Research Center, U.S. Army Medical Research Directorate-Africa, Kombewa, Kenya
| | - Michael A Eller
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD; and
| | - Dohoon Kim
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD; and
| | - Matthew Creegan
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD; and
| | - Allahna Esber
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD; and
| | - Leigh Anne Eller
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD; and
| | | | - Hannah Kibuuka
- Makerere University Walter Reed Project, Kampala, Uganda
| | | | - Trevor A Crowell
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD; and
| | - Christina S Polyak
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD; and
| | - Julie A Ake
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD
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Akbar SMF, Al Mahtab M, Cesar Aguilar J, Uddin MH, Khan MSI, Yoshida O, Penton E, Gerardo GN, Hiasa Y. Exploring evidence-based innovative therapy for the treatment of chronic HBV infection: experimental and clinical. EXPLORATION OF MEDICINE 2021. [DOI: 10.37349/emed.2021.00058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 08/03/2021] [Indexed: 01/02/2025] Open
Abstract
With the advent of various vaccines and antimicrobial agents during the 20th century, the control and containment of infectious diseases appeared to be a matter of time. However, studies unveiled the diverse natures of microbes, their lifestyle, and pathogenetic potentials. Since the ground-breaking discovery of the hepatitis B virus (HBV) by Baruch Blumberg and the subsequent development of a vaccine in the early 1980s, the main task of the scientific community has been to develop a proper management strategy for HBV-induced chronic liver diseases. In the early 1980’s, standard interferon (IFN) induced a reduction of HBV DNA levels, followed by the normalization of serum transaminases (alanine aminotransferase, ALT), in some chronic hepatitis B (CHB) patients. However, in the course of time, the limitations of standard IFN became evident, and the search for an alternative began. In the late 1980’s, nucleoside analogs entered the arena of CHB treatment as oral drugs with potent antiviral capacities. At the beginning of the 21st century, insights were developed into the scope and limitations of standard IFN, pegylated-IFN as well as nucleoside analogs for treating CHB. Considering the non-cytopathic nature of the HBV, the presence of covalently closed circular DNA (cccDNA) in the nucleus of the infected hepatocytes and HBV-induced immune-mediated liver damages, a new field of CHB management was initiated by modulating the hosts’ immune system through immune therapy. This review will discuss the nature and design of innovative immune therapy for CHB.
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Affiliation(s)
- Sheikh Mohammad Fazle Akbar
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime 7910295, Japan
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka 1000, Bangladesh
| | - Julio Cesar Aguilar
- Center for Genetic Engineering and Biotechnology, Havana, Havana 10600, Cuba
| | | | - Md. Sakirul Islam Khan
- Department of Anatomy and Embryology, Ehime University Graduate School of Medicine, Ehime 7910295, Japan
| | - Osamu Yoshida
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime 7910295, Japan
| | - Eduardo Penton
- Center for Genetic Engineering and Biotechnology, Havana, Havana 10600, Cuba
| | | | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime 7910295, Japan
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Mo S, Au L, Huang S, Malik P, Pan DH. Natural History of Chronic Hepatitis B Infection Among Chinese Children and Young Adults: A Single-Center Experience. J Pediatr Gastroenterol Nutr 2021; 73:150-155. [PMID: 33661243 DOI: 10.1097/mpg.0000000000003106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES There are limited data on the natural history of chronic hepatitis B virus (HBV) infection in Asian American children. The aim of the present study was to describe a single-center experience of chronic HBV infection in Chinese American patients in New York City. METHODS A retrospective chart review was conducted for patients with chronic HBV infection who had pediatric visits from 2006 to 2017. Clinical and laboratory data were collected to characterize the status of HBV infection and its disease course both cross-sectionally and longitudinally. Available maternal charts were reviewed. RESULTS Of the total 353 patients, 72 patients (20%) were US-born. Positive hepatitis B envelope antigen (HBeAg) was documented in 208 patients (58%). Three phases of chronic HBV infection were categorized for 329 patients: immune-tolerant 112 (34%), HBeAg-positive immune-active 47 (14%), and inactive carrier 82 (25%). The remaining 88 patients (27%) did not fit into a particular category with 26 of 88 patients meeting the criteria for inactive carrier except for mildly elevated alanine aminotransferase. Age and liver enzyme levels were significantly different between HBeAg-positive and HBeAg-negative groups (P < 0.05). Among 179 patients followed for ≥5 years, the spontaneous seroconversion rate was 38%. In eight patients with linked maternal data, all children completed the HBV vaccine series and seven of eight received hepatitis B immunoglobulin. All mothers were HBeAg-positive with high HBV DNA and had no anti-viral therapy during pregnancy. CONCLUSIONS Both immune-tolerant and inactive carrier phases were common for chronic HBV infection with a spontaneous seroconversion rate of 38%. All US-born patients were born in the era of implemented universal immune-prophylaxis.
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Affiliation(s)
- Shirley Mo
- Charles B. Wang Community Health Center
- The City University of New York School of Medicine, New York, NY
| | | | | | - Preeti Malik
- The Children's Hospital at Montefiore, Bronx, NY
| | - Debra H Pan
- Charles B. Wang Community Health Center
- The Children's Hospital at Montefiore, Bronx, NY
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22
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Buti M, Stepanova M, Palom A, Riveiro-Barciela M, Nader F, Roade L, Esteban R, Younossi Z. Chronic hepatitis D associated with worse patient-reported outcomes than chronic hepatitis B. JHEP Rep 2021; 3:100280. [PMID: 34041466 PMCID: PMC8141931 DOI: 10.1016/j.jhepr.2021.100280] [Citation(s) in RCA: 6] [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: 12/24/2020] [Revised: 03/08/2021] [Accepted: 03/09/2021] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND & AIMS Health-related quality of life (HRQoL) determined by patient-reported outcomes (PROs) is impaired in chronic hepatitis B (CHB) and C patients, but there are no data regarding patients with chronic hepatitis D (CHD). The aim of this study was to assess PRO scores in untreated patients with CHD and compare them with those obtained for patients with CHB. METHODS Patients with CHD completed 3 PRO instruments (Chronic Liver Disease Questionnaire [CLDQ], Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F], and Work Productivity and Activity Impairment [WPAI]), and the results were compared with those of patients mono-infected with CHB. RESULTS In total, 125 patients were included: 43 with CHD and 82 with CHB. Overall, baseline PROs showed differences between both groups. Several assessments, such as the worry score from CLDQ (p = 0.0118), functional well-being from FACIT-F (p = 0.0281), and activity impairment from WPAI (p = 0.0029) showed a significant trend to worse scores in patients with CHD than with CHB. In addition, the linear regression model supports the finding that having CHD as opposed to having CHB was a predictor of a higher worry score (CLDQ) and a higher activity impairment (WPAI). CONCLUSIONS In this first assessment in CHD, PROs recorded in patients with CHD showed a significant impairment in some domains of HRQoL questionnaires in comparison with those with CHB. Studies in larger cohorts with lengthier follow-up are needed to fully assess patient-reported quality of life over the course of CHD. LAY SUMMARY Chronic hepatitis D (CHD) is a viral disease that causes rapid evolution to liver cirrhosis, amongst other severe complications, when compared to patients with chronic hepatitis B (CHB). Health-related quality of life in chronic hepatitis C and CHB has been reported widely, but no studies have been performed on patient-reported outcomes in patients with CHD. Results showed that CHD patients reported worse outcomes in psychological domains such as worry and emotional well-being, as well as in physical domains such as abdominal symptoms, physical well-being, and activity impairment in comparison with patients with CHB.
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Key Words
- ALT, alanine aminotransferase
- APRI, AST to platelet ratio index
- AST, aspartate aminotransferase
- CHB, chronic hepatitis B
- CHC, chronic hepatitis C
- CHD, chronic hepatitis D
- CLDQ, Chronic Liver Disease Questionnaire
- Chronic Liver Disease Questionnaire
- DAA, direct-acting antivirals
- EMA, European medicines agency
- FACIT-F, Functional Assessment of Chronic Illness Therapy–Fatigue
- FIB-4, Fibrosis-4
- Functional Assessment of Chronic Illness Therapy–Fatigue
- HRQoL, health-related quality of life
- Health-related quality of life
- IFN, interferon
- LLOD, lower limit of detection
- LLOQ, lower limit of quantification
- NAs, nucleos(t)ide analogues
- PROs, patient-reported outcomes
- Viral hepatitis
- WPAI, Work Productivity and Activity Impairment
- Work Productivity Activity Impairment
- pegIFN, pegylated interferon
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Affiliation(s)
- Maria Buti
- Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus and Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Maria Stepanova
- Center for Outcomes Research in Liver Disease, Washington, DC, USA
| | - Adriana Palom
- Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus and Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Mar Riveiro-Barciela
- Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus and Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Fatema Nader
- Center for Outcomes Research in Liver Disease, Washington, DC, USA
| | - Luisa Roade
- Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus and Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Rafael Esteban
- Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus and Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Zobair Younossi
- Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA, USA
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
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Hamida ME, Raja SM, Seyoum Y, Elkhidir IM, Tekle F. Prevalence of chronic hepatitis B phases in Eritrean patients: a laboratory-based cross-sectional study. BMC Gastroenterol 2021; 21:198. [PMID: 33933017 PMCID: PMC8088660 DOI: 10.1186/s12876-021-01789-3] [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: 12/14/2020] [Accepted: 04/21/2021] [Indexed: 11/18/2022] Open
Abstract
Background Understanding the natural history of chronic hepatitis B (CHB) virus infection is important for determining optimal management and predicting prognosis in patients. The aim of this study was to determine the prevalence of different phases of CHB infection among Eritrean patients and to identify the proportion of patients who are eligible for treatment according to the latest American Association for the Study of Liver Diseases (AASLD) guidelines. Methods This cross-sectional study enrolled 293 CHB patients (213 males and 80 females) between Jan 2017 and Feb 2019. The patients were classified into immune-tolerant, immune-active, and inactive CHB phases of the infection, which is based on the results of Hepatitis B virus (HBV) serological panel (HBsAg, anti-HBc total, HBeAg, and anti-HBe), ALT levels, and HBV DNA viral load. The 2018 AASLD guidelines were also used to identify patients who needed treatment. Results The mean age of the patients was 41.66 ± 13.84 years. Of these, 3 (1.0%) were at the immune tolerant phase, 58 (19.8%) at the immune-active CHB phase, and 232 (79.2%) at the inactive CHB phase. As most subjects (93%) were HBeAg-negative, based on AASLD guidelines, only 5 (1.7%) were currently eligible for treatment. Conclusions Our data show that CHB patients in Eritrea were predominantly in the inactive CHB phase. Although initiating antiviral therapy is not recommended in these patients, periodic assessment of liver function and disease severity should be considered in patients older than 40 years. The immune-tolerant phase had the fewest patients, most of whom were aged above 20 years, attesting to the success of incorporating HBV vaccine in the national childhood immunization program since 2002. Our study shows that adopting AASLD treatment guidelines with adjustments to suit the local setting is a suitable option in the management of Eritrean CHB patients.
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Affiliation(s)
- Mohammed Elfatih Hamida
- Department of Microbiology, Orotta College of Medicine and Health Sciences (OCMHS), Asmara, Eritrea.
| | - Saud Mohammed Raja
- Department of Internal Medicine, Orotta College of Medicine and Health Sciences (OCMHS), Asmara, Eritrea
| | - Yemane Seyoum
- Department of Internal Medicine, Orotta College of Medicine and Health Sciences (OCMHS), Asmara, Eritrea
| | - Isam Mohammed Elkhidir
- Department of Microbiology, Faculty of Medicine, University of Khartoum, Khartoum, Sudan
| | - Freweini Tekle
- Department of Immunoserology, National Health Laboratory (NHL), Asmara, Eritrea
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Huang LL, Yu XP, Li JL, Lin HM, Kang NL, Jiang JJ, Zhu YY, Liu YR, Zeng DW. Effect of liver inflammation on accuracy of FibroScan device in assessing liver fibrosis stage in patients with chronic hepatitis B virus infection. World J Gastroenterol 2021; 27:641-653. [PMID: 33642834 PMCID: PMC7901051 DOI: 10.3748/wjg.v27.i7.641] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Revised: 12/30/2020] [Accepted: 01/13/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Transient elastography (FibroScan) is a new and non-invasive test, which has been widely recommended by the guidelines of chronic hepatitis B virus (HBV) management for assessing hepatic fibrosis staging. However, some confounders may affect the diagnostic accuracy of the FibroScan device in fibrosis staging.
AIM To evaluate the diagnostic value of the FibroScan device and the effect of hepatic inflammation on the accuracy of FibroScan in assessing the stage of liver fibrosis in patients with HBV infection.
METHODS The data of 416 patients with chronic HBV infection who accepted FibroScan, liver biopsy, clinical, and biological examination were collected from two hospitals retrospectively. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic performance of FibroScan for assessing the stage of liver fibrosis. Any discordance in fibrosis staging by FibroScan and pathological scores was statistically analyzed. Logistic regression and ROC analyses were used to analyze the accuracy of FibroScan in assessing the stage of fibrosis in patients with different degrees of liver inflammation. A non-invasive model was constructed to predict the risk of misdiagnosis of fibrosis stage using FibroScan.
RESULTS In the overall cohort, the optimal diagnostic values of liver stiffness measurement (LSM) using FibroScan for significant fibrosis (≥ F2), severe fibrosis (≥ F3), and cirrhosis (F4) were 7.3 kPa [area under the curve (AUC) = 0.863], 9.7 kPa (AUC = 0.911), and 11.3 kPa (AUC = 0.918), respectively. The rate of misdiagnosis of fibrosis stage using FibroScan was 34.1% (142/416 patients). The group of patients who showed discordance between fibrosis staging using FibroScan and pathological scores had significantly higher alanine aminotransferase and aspartate aminotransferase levels, and a higher proportion of moderate to severe hepatic inflammation, compared with the group of patients who showed concordance in fibrosis staging between the two methods. Liver inflammation activity over 2 (OR = 3.53) was an independent risk factor for misdiagnosis of fibrosis stage using FibroScan. Patients with liver inflammation activity ≥ 2 showed higher LSM values using FibroScan and higher rates of misdiagnosis of fibrosis stage, whereas the diagnostic performance of FibroScan for different fibrosis stages was significantly lower than that in patients with inflammation activity < 2 (all P < 0.05). A non-invasive prediction model was established to assess the risk of misdiagnosis of fibrosis stage using FibroScan, and the AUC was 0.701.
CONCLUSION Liver inflammation was an independent risk factor affecting the diagnostic accuracy of FibroScan for fibrosis stage. A combination of other related non-invasive factors can predict the risk of misdiagnosis of fibrosis staging using FibroScan.
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Affiliation(s)
- Ling-Ling Huang
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Xue-Ping Yu
- Department of Infectious Diseases, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou 362000, Fujian Province, China
| | - Ju-Lan Li
- Department of Infectious Diseases, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou 362000, Fujian Province, China
| | - Hui-Ming Lin
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Na-Ling Kang
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Jia-Ji Jiang
- Department of Hepatology, Hepatology Research Institute, 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, Fuzhou 350005, Fujian Province, China
- Fujian Key Laboratory of Precision Medicine for Cancer, Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Yu-Rui Liu
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Da-Wu Zeng
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
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Lucas B, Ravishankar S, Pateva I. Pediatric Primary Hepatic Tumors: Diagnostic Considerations. Diagnostics (Basel) 2021; 11:333. [PMID: 33670452 PMCID: PMC7922091 DOI: 10.3390/diagnostics11020333] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 02/12/2021] [Accepted: 02/15/2021] [Indexed: 02/06/2023] Open
Abstract
The liver is the third most common site of abdominal tumors in children. This review article aims to summarize current evidence surrounding identification and diagnosis of primary hepatic tumors in the pediatric population based upon clinical presentation, epidemiology, and risk factors as well as classical imaging, histopathological, and molecular diagnostic findings. Readers will be able to recognize the features and distinguish between benign and malignant hepatic tumors within different age groups.
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Affiliation(s)
- Bryony Lucas
- Rainbow Babies and Children’s Hospital—Department of Pediatrics, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA
| | - Sanjita Ravishankar
- Rainbow Babies and Children’s Hospital—Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA
| | - Irina Pateva
- Rainbow Babies and Children’s Hospital—Department of Pediatric Hematology and Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA
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Effects of nucleo(s)tide analogs therapy on chronic hepatitis B as evaluated by hepatosplenic radionuclide angiography. Nucl Med Commun 2021; 41:314-319. [PMID: 31939901 DOI: 10.1097/mnm.0000000000001156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVES Hepatosplenic radionuclide angiography is a relatively noninvasive method for evaluating hepatic portal perfusion. We used hepatosplenic radionuclide angiography to assess the effects of nucleo(s)tide analogs therapy on patients with chronic hepatitis B (CHB). PATIENTS AND METHODS A retrospective analysis was performed on patients who underwent hepatosplenic radionuclide angiography from January 2012 to May 2017 at the First Affiliated Hospital, College of Medicine, Zhejiang University. The correlations between the results of routine laboratory tests and hepatic perfusion index (HPI) were evaluated. The Wilcoxon signed-rank test and one-way ANOVA of repeated measures were used to compare the HPIs of patients who received nucleo(s)tide analogs therapy. RESULTS There is a positive correlation between HPI and cholinesterase and serum albumin (ALB) and a negative correlation between HPI and aspartate aminotransferase-to-platelet ratio index and bilirubin (TBiL). An improvement in HPI was observed in patients with an initial HPI <61% after nucleo(s)tide analogs therapy. CONCLUSIONS Hepatosplenic radionuclide angiography can reflect the functional reserve of the liver and monitor liver fibrosis indirectly. It can also comprehensively assess the effects of antiviral therapy on patients with CHB, and antiviral therapy is critical for the treatment of hepatitis.
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Kang NL, Zhang JM, Lin MX, Chen XD, Huang ZX, Zhu YY, Liu YR, Zeng DW. Serum ceruloplasmin can predict liver fibrosis in hepatitis B virus-infected patients. World J Gastroenterol 2020; 26:3952-3962. [PMID: 32774069 PMCID: PMC7385565 DOI: 10.3748/wjg.v26.i27.3952] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Revised: 05/06/2020] [Accepted: 06/29/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The presence of significant liver fibrosis in hepatitis B virus (HBV)-infected individuals with persistently normal serum alanine aminotransferase (PNALT) levels is a strong indicator for initiating antiviral therapy. Serum ceruloplasmin (CP) is negatively correlated with liver fibrosis in HBV-infected individuals.
AIM To examine the potential value of serum CP and develop a noninvasive index including CP to assess significant fibrosis among HBV-infected individuals with PNALT.
METHODS Two hundred and seventy-five HBV-infected individuals with PNALT were retrospectively evaluated. The association between CP and fibrotic stages was statistically analyzed. A predictive index including CP [Ceruloplasmin hepatitis B virus (CPHBV)] was constructed to predict significant fibrosis and compared to previously reported models.
RESULTS Serum CP had an inverse correlation with liver fibrosis (r = -0.600). Using CP, the areas under the curves (AUCs) to predict significant fibrosis, advanced fibrosis, and cirrhosis were 0.774, 0.812, and 0.853, respectively. The CPHBV model was developed using CP, platelets (PLT), and HBsAg levels to predict significant fibrosis. The AUCs of this model to predict significant fibrosis, advanced fibrosis, and cirrhosis were 0.842, 0.920, and 0.904, respectively. CPHBV was superior to previous models like the aspartate aminotransferase (AST)-to-PLT ratio index, Fibrosis-4 score, gamma-glutamyl transpeptidase-to-PLT ratio, Forn’s score, and S-index in predicting significant fibrosis in HBV-infected individuals with PNALT.
CONCLUSION CPHBV could accurately predict liver fibrosis in HBV-infected individuals with PNALT. Therefore, CPHBV can be a valuable tool for antiviral treatment decisions.
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Affiliation(s)
- Na-Ling Kang
- Liver Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Jie-Min Zhang
- Department of Pharmacy, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Meng-Xin Lin
- Department of Infectious Diseases, The First Hospital of Quanzhou Affiliated with Fujian Medical University, Quanzhou 362000, Fujian Province, China
| | - Xu-Dong Chen
- Department of Gastroenterology, the 910th Hospital of the People's Liberation Army, Quanzhou 362000, Fujian Province, China
| | - Zu-Xiong Huang
- Hepatology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Yue-Yong Zhu
- Liver Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Yu-Rui Liu
- Liver Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Da-Wu Zeng
- Liver Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
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Raihan R, Akbar SMF, Al Mahtab M, Khan MSI, Tabassum S, Tee KK, Mohamed RB. Increased Proinflammatory Cytokine Production by Chronic Hepatitis B Patients with Mutant Hepatitis B Virus: Plausible Mechanisms Underlying Severe Liver Diseases in These Patients. Viral Immunol 2020; 33:530-534. [PMID: 32513066 DOI: 10.1089/vim.2019.0198] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Hepatitis B virus (HBV) is a noncytopathic virus and billions of HBV-infected patients live uneventful lives and do not suffer from notable liver damage. However, HBV also causes progressive liver diseases characterized by hepatic inflammation, hepatic fibrosis, and liver cancer in millions of HBV-infected patients. The goal of this study was to evaluate the role of mutant HBV in HBV pathogenesis. In a cohort of 360 chronic HBV-infected patients, mutations at T1762/A1764 of HBV genome were detected in most of the patients with HBV-induced liver cirrhosis and hepatocellular carcinoma. To explore if mutations at T1762/A1764 of HBV genome has any role in progressive liver disease, peripheral blood mononuclear cells (PBMCs) and antigen-presenting dendritic cells (DCs) were isolated from five chronic hepatitis B (CHB) patients with mutations at T1762/A1764 and five comparable patients of CHB without mutations at T1762/A1764. DCs were pulsed with hepatitis B surface antigen (HBsAg). The levels of cytokines produced by PBMCs and DCs as well as nitrite production by DCs were evaluated. Significantly higher levels of interleukin-12, tumor necrosis factor-alpha, interferon-gamma, and transforming growth factor-beta were detected in cultures of PBMCs, DCs, and HBsAg-pulsed DCs from CHB patients with mutations at T1762/A1764 compared with those without mutations (p < 0.05). DCs of all CHB patients with mutations produced significantly higher levels of nitrite compared with those without mutation at T1762/A1764 (p < 0.001). This study discusses the inflammatory potential of mutant HBV that may be responsible for diverse levels of pathogenicity of HBV. Further studies involving larger cohorts would provide more insight into these unresolved issues about HBV pathogenesis and these insights may aid in developing immune therapy for CHB patients.
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Affiliation(s)
- Ruksana Raihan
- Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Sheikh Mohammad Fazle Akbar
- Department of Pathology, Ehime University Proteo-Science Center, Ehime University Graduate School of Medicine, Toon City, Japan.,Miyakawa Memorial Research Foundation, Tokyo, Japan
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Md Sakirul Islam Khan
- Department of Anatomy and Embryology, Ehime University Graduate School of Medicine, Matsuyama, Japan
| | - Shahina Tabassum
- Department of Virology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Kok Keng Tee
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.,School of Healthcare and Medical Sciences, Sunway University, Bandar Sunway, Malaysia
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Lenci I, Milana M, Grassi G, Manzia TM, Gazia C, Tisone G, Angelico R, Baiocchi L. Hepatitis B virus recurrence after liver transplantation: An old tale or a clear and present danger? World J Gastroenterol 2020; 26:2166-2176. [PMID: 32476783 PMCID: PMC7235198 DOI: 10.3748/wjg.v26.i18.2166] [Citation(s) in RCA: 10] [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: 02/11/2020] [Revised: 03/12/2020] [Accepted: 04/30/2020] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) recurrence after liver transplantation (LT) has been described more than 50 years ago. Similarly, to other clinical conditions, in which impairment of host immune defense favors viral replication, early reports described in details recurrence and reactivation of HBV in liver transplant recipients. The evidence of a possible, severe, clinical evolution of HBV reappearance in a significant percentage of these patients, allowed to consider, for some years, HBV positivity a contraindication for LT. Moving from the old to the new millennium this picture has changed dramatically. Several studies contributed to establish efficient prophylactic protocols for HBV recurrence and with the advent of more potent anti-viral drugs an increased control of infection was achieved in transplanted patients as well as in the general immune-competent HBV population. Success obtained in the last decade led some authors to the conclusion that HBV is now to consider just as a “mere nuisance”. However, with regard to HBV and LT, outstanding issues are still on the table: (1) A standard HBV prophylaxis protocol after transplant has not yet been clearly defined; (2) The evidence of HBV resistant strains to the most potent antiviral agents is claiming for a new generation of drugs; and (3) The possibility of prophylaxis withdrawal in some patients has been demonstrated, but reliable methods for their selection are still lacking. The evolution of LT for HBV is examined in detail in this review together with the description of the strategies adopted to prevent HBV recurrence and their pros and cons.
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Affiliation(s)
- Ilaria Lenci
- Hepatology and Liver Transplant Unit, University of Tor Vergata, Rome 00133, Italy
| | - Martina Milana
- Hepatology and Liver Transplant Unit, University of Tor Vergata, Rome 00133, Italy
| | - Giuseppe Grassi
- Hepatology and Liver Transplant Unit, University of Tor Vergata, Rome 00133, Italy
| | - Tommaso M Manzia
- Hepato-Pancreato-Biliary and Transplant, Department of Surgery, University of Rome Tor Vergata, Rome 00133, Italy
| | - Carlo Gazia
- Hepato-Pancreato-Biliary and Transplant, Department of Surgery, University of Rome Tor Vergata, Rome 00133, Italy
| | - Giuseppe Tisone
- Hepato-Pancreato-Biliary and Transplant, Department of Surgery, University of Rome Tor Vergata, Rome 00133, Italy
| | - Roberta Angelico
- Hepato-Pancreato-Biliary and Transplant, Department of Surgery, University of Rome Tor Vergata, Rome 00133, Italy
| | - Leonardo Baiocchi
- Hepatology and Liver Transplant Unit, University of Tor Vergata, Rome 00133, Italy
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Wang L, Sun Y, Yi M, Zhao W, Yuan X. IEO model: A novel concept describing the complete metastatic process in the liver microenvironment. Oncol Lett 2020; 19:3627-3633. [PMID: 32391088 DOI: 10.3892/ol.2020.11525] [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: 07/17/2019] [Accepted: 01/16/2020] [Indexed: 11/06/2022] Open
Abstract
Metastasis is a characteristic behavior of malignant tumor cells. It is determined by the mutual interaction between primary tumor cells and the state of the microenvironment at sites of metastasis, particularly the liver, bone, lungs and brain. In the present review, a novel pattern is defined and termed the IEO model (prI-, prE- and pOst-metastatic niche), for the hepatic metastatic microenvironment which characterizes the complete metastatic process. In the IEO model, the components of the hepatic metastatic niche, including the extracellular matrix, hepatocytes, mesenchymal cells, Kupffer cells, hepatic sinusoidal endothelial cells, hepatic stellate cells and immunocytes are continually remodelled by tumor cells to form various microenvironments during different stages of hepatic metastasis. The IEO model explains the plasticity of the hepatic microenvironment and provides novel insights into the role of different stages of the metastatic niche. This novel concept may provide a basis for advances in theoretical cancer research and for improvements in the complete course management of malignant tumors.
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Affiliation(s)
- Lu Wang
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
| | - Yinan Sun
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
| | - Minxiao Yi
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
| | - Weiheng Zhao
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
| | - Xianglin Yuan
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
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Geng J, Bao H, Chen Y, Shi L, Geng J, Wang Q, Yu H. Nucleos(t)ide analogues for the treatment of chronic hepatitis B: a systematic review with network meta-analysis. Expert Rev Anti Infect Ther 2020; 18:823-834. [PMID: 32329638 DOI: 10.1080/14787210.2020.1760843] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
OBJECTIVES Chronic hepatitis B (CHB) is a major global health problem caused by hepatitis B virus (HBV) infection, and can put patients at high risk of death from cirrhosis and liver cancer. However, CHB can be treated with nucleos(t)ide analogues. We aimed to evaluate the effectiveness and safety of nucleos(t)ide analogues for the treatment of CHB patients. METHODS A systematic literature search was performed. Direct comparison meta-analyses and network meta-analysis (NMA) were carried out. RESULTS Thirty-six randomized controlled trials (RCTs) met inclusion criteria. Compared with placebo, the nucleos(t)ide analogues were all effective in HBeAg seroconversion, HBeAg loss, and achieving undetectable HBV DNA. Telbivudine was associated with higher HBeAg seroconversion compared with entecavir. For HBeAg loss rate and proportion of achieving undetectable HBV DNA, tenofovir ranked as the best. Entecavir might be the most potent in the normalization of alanine aminotransferase (ALT). The nucleos(t)ide analogues did not have higher serious adverse events rate as compared with placebo. CONCLUSION The nucleos(t)ide analogues are all effective for HBeAg seroconversion, HBeAg loss, undetectable HBV DNA, and most are effective for ALT normalization in adults with CHB. RCTs of multi-center, low risk of bias, and long-term follow-up are still needed.
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Affiliation(s)
- JinSong Geng
- Evidence-based Medicine Center, Medical School of Nantong University , Jiangsu, China
| | - HaiNi Bao
- Evidence-based Medicine Center, Medical School of Nantong University , Jiangsu, China
| | - YaLan Chen
- Evidence-based Medicine Center, Medical School of Nantong University , Jiangsu, China
| | - LiLi Shi
- Evidence-based Medicine Center, Medical School of Nantong University , Jiangsu, China
| | - Jing Geng
- Department of Gastroenterology, Lianyungang No 1 People's Hospital , Jiangsu, China
| | - Qing Wang
- Department of Infectious Disease, Ningxiang People's Hospital , Hunan, China
| | - Hao Yu
- Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute , Boston, MA, USA
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Aurpibul L, Kanjanavanit S, Leerapun A, Puthanakit T. Risk of Liver Fibrosis in Hepatitis B Virus and HIV Coinfected Youths Receiving Tenofovir-Containing Antiretroviral Regimen. J Int Assoc Provid AIDS Care 2020; 18:2325958218823259. [PMID: 30798669 PMCID: PMC6748531 DOI: 10.1177/2325958218823259] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) and HIV coinfection is associated with risk of progression to chronic liver disease. We assessed liver stiffness in HBV-HIV coinfected youths. METHODS A cross-sectional study in HBV-HIV coinfected youths aged 18 to 25 years who received a tenofovir (TDF)-containing antiretroviral therapy regimen for >96 weeks. Measurements included HBV DNA level, HBV serology profiles, and transient elastography (TE). The cutoff for TE results included ≥5.9 kPa for F2-moderate fibrosis, ≥7.4 kPa for F3-severe fibrosis, and ≥9.6 kPa for F4-cirrhosis. RESULTS From March to December 2016, 15 HBV-HIV coinfected youths with a median duration on TDF-containing regimens of 3.3 years were enrolled. Five (33%) youths had significant liver fibrosis, 3 with F2-moderate, 1 with F3-advanced fibrosis, and 1 with F4-cirrhosis. Other 5 without liver fibrosis had hepatitis B surface e antigen (HBsAg) and hepatitis B surface e antigen (HBeAg) loss. Higher mean alanine transaminase (ALT) was observed among the group with F2-F4 when compared to those with F0. CONCLUSION Liver fibrosis was evidenced in HBV-HIV coinfected youths in Thailand. Transient elastography might be considered for those who do not achieve HBsAg loss or have persistent ALT elevation while on treatment.
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Affiliation(s)
- Linda Aurpibul
- 1 Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand
| | | | - Apinya Leerapun
- 3 Division of Gastroenterology, Department of internal medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Thanyawee Puthanakit
- 4 The HIV Netherlands, Australia, Thailand Research Collaboration (HIVNAT), Bangkok, Thailand.,5 Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.,6 Center of Excellence in Pediatric Infectious Diseases and Vaccines, Chulalongkorn University, Bangkok, Thailand
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Tian F, Houle SKD, Alsabbagh MW, Wong WWL. Cost-Effectiveness of Tenofovir Alafenamide for Treatment of Chronic Hepatitis B in Canada. PHARMACOECONOMICS 2020; 38:181-192. [PMID: 31691902 DOI: 10.1007/s40273-019-00852-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
BACKGROUND/AIM Tenofovir alafenamide (TAF) has been approved for treating chronic hepatitis B (CHB) due to a proposed better safety profile in comparison with current therapies. We evaluated the cost effectiveness of TAF and other available treatment options for hepatitis B envelope antigen (HBeAg)-positive and HBeAg-negative CHB patients from a Canadian provincial Ministry of Health perspective. METHODS A state-transition model based on the published literature was developed to compare treatment strategies involving entecavir (ETV), tenofovir disoproxil fumarate (TDF), and TAF. It adopted a lifetime time horizon. Outcomes measured were predicted number of liver-related deaths, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS For HBeAg-positive patients, TAF followed by ETV generated an additional 0.16 QALYs/person at an additional cost of Can$14,836.18 with an ICER of Can$94,142.71/QALY compared with TDF followed by ETV. Of the iterations, 28.7% showed that it is the optimal strategy with a Can$50,000 willingness-to-pay threshold. For HBeAg-negative patients, ETV followed by TAF would prevent an additional 13 liver-related deaths per 1000 CHB patients compared with TDF, followed by ETV. It generated an additional 0.13 QALYs/person at an additional cost of Can$59,776.53 with an ICER of Can$461,162.21/QALY compared with TDF, followed by ETV. TAF-containing strategies are unlikely to be a rational choice in either case. The results were sensitive to the HBeAg seroconversion rates and viral suppression rates of the treatments. CONCLUSIONS Our analysis suggests that TAF is not cost effective at its current cost. A 33.4% reduction in price would be required to make it cost effective for HBeAg-positive patients with a Can$50,000 willingness-to-pay threshold.
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Affiliation(s)
- Feng Tian
- School of Pharmacy, Faculty of Science, University of Waterloo, 10A Victoria Street S, Kitchener, ON, N2G1C5, Canada
| | - Sherilyn K D Houle
- School of Pharmacy, Faculty of Science, University of Waterloo, 10A Victoria Street S, Kitchener, ON, N2G1C5, Canada
| | - Mhd Wasem Alsabbagh
- School of Pharmacy, Faculty of Science, University of Waterloo, 10A Victoria Street S, Kitchener, ON, N2G1C5, Canada
| | - William W L Wong
- School of Pharmacy, Faculty of Science, University of Waterloo, 10A Victoria Street S, Kitchener, ON, N2G1C5, Canada.
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Di Bona D, Pandey JP, Aiello A, Bilancia M, Candore G, Caruso C, Colomba C, Duro G, Ligotti ME, Macchia L, Rizzo S, Accardi G. The immunoglobulin γ marker 17 allotype and KIR/HLA genes prevent the development of chronic hepatitis B in humans. Immunology 2019; 159:178-182. [PMID: 31613998 DOI: 10.1111/imm.13133] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Revised: 09/18/2019] [Accepted: 10/09/2019] [Indexed: 01/02/2023] Open
Abstract
Hepatitis B virus (HBV) infection causes a self-limiting disease in most individuals. However, < 10% of infected subjects develop a chronic disease. Genetic host variability of polymorphic genes at the interface of innate and acquired immunity, such as killer immunoglobulin-like receptors (KIR), their human leucocyte antigen (HLA) and IgG allotypes (GM), could explain this different clinical picture. We previously showed a protective role of the KIR2DL3 gene for the development of chronic hepatitis B (CHB), and a detrimental role of the KIR ligand groups, HLA-A-Bw4 and HLA-C2. We have expanded the previous analysis genotyping patients for GM23 and GM3/17 allotypes. The comparison of the patients with CHB with those who resolved HBV infection showed that the presence of GM17 allele virtually eliminated the risk of developing CHB (OR, 0·03; 95% CI, 0·004-0·16; P < 0·0001). In addition, the combination of GM17, KIR2DL3, HLA-A-Bw4 and HLA-C2 was highly sensitive to predict the outcome of HBV infection.
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Affiliation(s)
- Danilo Di Bona
- Dipartimento dell'Emergenza e dei Trapianti d'Organo, Università di Bari Aldo Moro, Bari, Italy
| | - Janardan P Pandey
- Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA
| | - Anna Aiello
- Laboratorio di Immunopatologia e Immunosenescenza, Dipartimento di Biomedicina, Neuroscienze e Diagnostica Avanzata, Università di Palermo, Palermo, Italy
| | - Massimo Bilancia
- Dipartmento Jonico in Sistemi Giuridici ed Economici del Mediterraneo: società, ambiente, culture, Università di Bari Aldo Moro, Bari, Italy
| | - Giuseppina Candore
- Laboratorio di Immunopatologia e Immunosenescenza, Dipartimento di Biomedicina, Neuroscienze e Diagnostica Avanzata, Università di Palermo, Palermo, Italy
| | - Calogero Caruso
- Laboratorio di Immunopatologia e Immunosenescenza, Dipartimento di Biomedicina, Neuroscienze e Diagnostica Avanzata, Università di Palermo, Palermo, Italy
| | - Claudia Colomba
- Dipartimento di Scienze per la Promozione della Salute e Materno-Infantile 'G. D'Alessandro', Università di Palermo, Palermo, Italy
| | - Giovanni Duro
- Istituto di Biomedicina ed Immunologia Molecolare, Consiglio Nazionale delle Ricerche, Palermo, Italy
| | - Mattia Emanuela Ligotti
- Laboratorio di Immunopatologia e Immunosenescenza, Dipartimento di Biomedicina, Neuroscienze e Diagnostica Avanzata, Università di Palermo, Palermo, Italy
| | - Luigi Macchia
- Dipartimento dell'Emergenza e dei Trapianti d'Organo, Università di Bari Aldo Moro, Bari, Italy
| | - Sergio Rizzo
- Unità Operativa di Medicina Trasfusionale, AOUP, Palermo, Italy
| | - Giulia Accardi
- Laboratorio di Immunopatologia e Immunosenescenza, Dipartimento di Biomedicina, Neuroscienze e Diagnostica Avanzata, Università di Palermo, Palermo, Italy
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Younossi ZM, Stepanova M, Younossi I, Papatheodoridis G, Janssen HLA, Agarwal K, Nguyen MH, Gane E, Tsai N, Nader F. Patient-reported outcomes in patients chronic viral hepatitis without cirrhosis: The impact of hepatitis B and C viral replication. Liver Int 2019; 39:1837-1844. [PMID: 31173468 DOI: 10.1111/liv.14171] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Revised: 05/27/2019] [Accepted: 05/29/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIM Chronic infections with hepatitis B or C (HBV and HCV) are associated with adverse clinical outcomes and patient-reported outcomes (PROs). The aim is to compare PRO scores in patients with chronic HBV and HCV without advanced liver disease before and after suppression/clearance of their infection. METHODS Patients with HCV and HBV infection prior to initiation of antiviral treatment and after viral suppression/eradication completed PRO questionnaires. RESULTS We included 132 patients with HBV and 132 matched patients with HCV. Baseline PRO scores were significantly higher in patients with HBV in the domains of Physical Functioning, Role Physical, Bodily Pain, Social Functioning, and Role Emotional of SF-36, SF-6D utility, Emotional and Fatigue domains of CLDQ, Presenteeism and total Work Productivity Impairment of WPAI:SHP in comparison to patients with HCV by 5.8%-13.2% of a PRO score range (all P < 0.05). After viral suppression (HBV DNA < 20 IU/mL after 48 weeks of treatment for HBV) or eradication (SVR-12 for HCV), only Physical Functioning and Role Physical scores remained higher in HBV by 6.7%-9.9%, while other PRO scores became similar between HBV and HCV groups (P > 0.05). The most prominent improvement of PROs in HCV was noted in Vitality, Emotional, Fatigue and Worry domains. In addition, General Health, Worry and Work Productivity scores were the most improved in HBV. CONCLUSIONS Prior to treatment, PRO scores were lower in patients with HCV in comparison to HBV. After successful treatment, both groups of patients experienced improvement in some PRO domains confirming the positive impact of treatment.
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Affiliation(s)
- Zobair M Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia.,Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia
| | - Maria Stepanova
- Center for Outcomes Research in Liver Disease, Washington, District of Columbia
| | - Issah Younossi
- Center for Outcomes Research in Liver Disease, Washington, District of Columbia
| | | | - Harry L A Janssen
- Toronto Centre for Liver Disease, University Health Network, Toronto, Canada
| | - Kosh Agarwal
- Institute of Liver Studies, London, United Kingdom
| | | | - Ed Gane
- Auckland Clinical Studies, Auckland, New Zealand
| | - Naoky Tsai
- Queens Medical Center, University of Hawaii, Honolulu, Hawaii
| | - Fatema Nader
- Center for Outcomes Research in Liver Disease, Washington, District of Columbia
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Akao T, Onji M, Kawasaki K, Uehara T, Kuwabara Y, Nishimoto T, Yamamoto S, Miyaike J, Oomoto M, Miyake T. Surveillance of Hepatitis Viruses in Several Small Islands of Japan by Ship: A Public Health Approach for Elimination of Hepatitis Viruses by 2030. Euroasian J Hepatogastroenterol 2019; 9:57-62. [PMID: 32117691 PMCID: PMC7047309 DOI: 10.5005/jp-journals-10018-1304] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
Aim In 1990, an epidemiological survey by ship in some Japanese islands revealed high prevalence of hepatitis viruses and human T cell leukemia virus (HTLV). A second prevalence study of these viruses were accomplished in 2018, 28 years after initial survey. Analysis of these studies provide insights about strategies of elimination of hepatitis viruses at remote areas. Materials and methods In 2018, prevalence of hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), and HTLV was checked in 305 subjects in the islands those covered in 1990's survey. Hepatitis A virus was checked by the presence of anti-HAV IgG in sera; HBV was affirmed when hepatitis B surface antigen (HBsAg) in sera. Hepatitis C virus infection was evaluated by the presence of antibody to HCV (anti-HCV) and infection with HTLV was estimated by immunoassay. The methodology of assessment of different hepatitis viruses were optimized on the basis of present scientific knowhow. Results In 1990, the prevalence of HAV (presence of anti-HAV), HBV (presence of HBsAg), HCV (positivity for anti-HCV), and HTLV was found in 79.3%, 11.1%, 2.2%, and 3.3% of apparently health subjects of the islands, respectively. The prevalence of HAV, HBV, HCV, and HTLV was 47.9%, 4.6%, 1.0%, and 3.0%, respectively, in 2018. A shift of age of infected persons tilted towards right as the days progressed. Conclusion The study indicates a scenario of elimination of hepatitis viruses in Japan as lower trends of prevalence of HAV, HBV, and HCV have been recorded in 2018 compared with 1990, mainly by preventive measures. The most notable finding is that there are almost no new case below the age of 40 years, indicating an effective containment measure against these viruses. How to cite this article Akao T, Onji M, Kawasaki K, et al. Surveillance of Hepatitis Viruses in Several Small Islands of Japan by Ship: A Public Health Approach for Elimination of Hepatitis Viruses by 2030. Euroasian J Hepato-Gastroenterol 2019;9(2):57–62.
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Affiliation(s)
| | - Morikazu Onji
- Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | | | | | | | | | | | - Jiro Miyaike
- Saiseikai Imabari Hospital, Imabari, Ehime, Japan
| | | | - Teruki Miyake
- Ehime University Graduate School of Medicine, Toon, Ehime, Japan
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Ashtari S, Sharifian A, Hatami B, Mohebbi SR, Nouri G, Bazdar M, Naderi N. Comparative study on guidelines in determining HBV phases in Iranian patients. GASTROENTEROLOGY AND HEPATOLOGY FROM BED TO BENCH 2019; 12:S145-S148. [PMID: 32099615 PMCID: PMC7011065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
AIM The aim of this study was to compare the different phases of chronic Hepatitis B virus (HBV) infection with different values for normal ALT. BACKGROUND For many years, the upper limit of 40 IU was considered normal for ALT for both sexes, but in recent years this value is challenged and some guidelines have lowered their limit. METHODS In this cross-sectional study, 2000 HBsAg positive patients who were referred to Taleghani Hospital, Tehran, Iran, from 2011 through 2018 were classified in four groups according to American Association of the study of the liver disease (AASLD), European Association of the study of the liver (EASL) /Asian-Pacific Association of the study of the liver (APASL) and American Collage of Gastroenterology (ACG) guidelines. The frequency of each group based on 3 different guidelines was compared. RESULTS In HBeAg positive patients (n=100), the percentage of immune tolerance phase was 43% according to AASLD cutoff for normal ALT (35 IU for men, 25 IU for women), while it was 68% and 28% with regard to EASL/APASL and ACG (30 IU for men, 19 IU for women) cutoffs respectively. In HBeAg negative patients (n=1900), 66.68% were inactive carriers according to AASLD, but the percentage changed to 82.89% and 52.42% considering EASL/APASL and ACG values, respectively. CONCLUSION Using ACG and to a lesser extent AASLD cutoff for ALT, many patients shift from immune tolerance and inactive carrier state into the immune active phase. Thus, more patients are candidates for treatment or intensive workup to determine the extent of liver damage.
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Affiliation(s)
- Sara Ashtari
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Afsaneh Sharifian
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Behzad Hatami
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed Reza Mohebbi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Gholamreza Nouri
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Monireh Bazdar
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nosratollah Naderi
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Liu C, Wang L, Xie H, Zhang L, Wang B, Luo C, Wang S, Tang M, Fu Z, Ruan H, Liu Z, Wei L, Yi W, Xie Y. The relationship between serum hepatitis B virus DNA level and liver histology in patients with chronic HBV infection. PLoS One 2018; 13:e0206060. [PMID: 30403735 PMCID: PMC6221304 DOI: 10.1371/journal.pone.0206060] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2018] [Accepted: 10/06/2018] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND There is no consensus regarding the relationship between HBV DNA and liver fibrosis, and the relationship between HBV DNA and the degree of liver cirrhosis has not been reported in patients with chronic HBV infection. METHODS From January 2011 to December 2016, liver biopsies were performed on 396 patients with chronic hepatitis B and cirrhosis. Assessments of liver fibrosis and cirrhosis were based on the Laennec staging system. RESULTS Serum levels of HBV DNA were correlated with fibrosis and cirrhosis (KW = 73.946, P<0.001). Serum HBV DNA level was correlated with mild fibrosis, moderate to severe fibrosis and cirrhosis (P = 0.009, P<0.001, and P<0.001, respectively). The HBeAg-positive group and HBeAg-negative group showed significant differences in HBV DNA levels, and the rates of mild fibrosis, severe fibrosis and cirrhosis were significantly different between these two groups (F = 17.585, P<0.001 and F = 6.017, P = 0.003, respectively). The replication status of the serum HBV DNA affected fibrosis formation as well as cirrhosis (χ2 = 53.76, P<0.001). In the HBeAg-positive group, the sensitivity, specificity and AUC values of HBV DNA as a predictor for mild fibrosis and cirrhosis were 64.3%, 78.94% and 0.818, respectively, and 81.0%, 69.2%, and 0.871, respectively. In the HBeAg-negative group, the sensitivity, specificity and AUC values of HBV DNA for liver sclerosis prediction were 48%, 76.8% and 0.697, respectively. CONCLUSIONS Different HBV DNA levels had different effects on the formation of fibrosis and sclerosis in liver tissues. HBV DNA levels can predict mild fibrosis and cirrhosis in liver tissue, which is enhanced in HBeAg-positive patients.
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Affiliation(s)
- Changjiang Liu
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, China
| | - Li Wang
- Department of Pathology, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, China
| | - Huizhong Xie
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, China
- * E-mail:
| | - Liyuan Zhang
- Department of Infectious Diseases, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, China
| | - Bingshu Wang
- Department of Pathology, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, China
| | - Chun Luo
- Department of Pathology, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, China
| | - Suiqun Wang
- Department of Pathology, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, China
| | - Mingliang Tang
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, China
| | - Zhongbiao Fu
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, China
| | - Hailan Ruan
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, China
| | - Zhengjin Liu
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, China
| | - Ling Wei
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, China
| | - Wenyi Yi
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, China
| | - Yunqian Xie
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, China
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Increased CCR7 loPD-1 hiCXCR5 +CD4 + T Cells in Peripheral Blood Mononuclear Cells Are Correlated with Immune Activation in Patients with Chronic HBV Infection. Can J Gastroenterol Hepatol 2018; 2018:1020925. [PMID: 30402448 PMCID: PMC6196997 DOI: 10.1155/2018/1020925] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Revised: 07/06/2018] [Accepted: 09/30/2018] [Indexed: 02/07/2023] Open
Abstract
T follicular helper cells (Tfh cells) affect essential immune pathogenesis in chronic hepatitis B virus (HBV) infection. The CCR7loPD-1hi Tfh subset has a partial Tfh effector phenotype and is associated with active Tfh differentiation, whereas the CCR7hiPD-1lo Tfh subset is a resting phenotype. We recruited 20 healthy volunteers and 77 patients with chronic HBV infection, including those in the immune tolerant (IT) phase (n=19), immune clearance (IC) phase (n=20), low replicative (LR) phase (n=18), and reactivation (RA) phase (n=20). The expression of CD4, CXCR5, PD-1, and CCR7 was detected in T cells from peripheral blood by flow cytometry. The frequency of the CCR7loPD-1hi T subset was significantly higher in the patients than in the healthy controls (14.92±4.87% vs 12.23±2.95%, p=0.018). The frequency of this Tfh subset in the IC group (18.42%±3.08) was increased compared with the IT group (11.94±2.87%, p=0.001) and LR group (13.65±4.93%, p=0.031) and was higher in the RA group than in the IT group (16.03±5.37% vs 11.94±2.87%, p=0.030). We observed a weak positive correlation between the CCR7loPD-1hi Tfh subset population and the alanine transaminase (ALT) level (r=0.370, p=0.001). The CCR7loPD-1h Tfh subset in the chronic HBV-infected patients was elevated to various degrees among the different immune phases. CCR7loPD-1hiCXCR5+CD4+ T cells are correlated with the immune status of chronic HBV infection patients and may be developed as a potential indicator for antiviral treatment.
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Younossi ZM, Stepanova M, Janssen HLA, Agarwal K, Nguyen MH, Gane E, Tsai N, Younossi I, Racila A. Effects of Treatment of Chronic Hepatitis B Virus Infection on Patient-Reported Outcomes. Clin Gastroenterol Hepatol 2018; 16:1641-1649.e6. [PMID: 29505905 DOI: 10.1016/j.cgh.2018.02.037] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2018] [Revised: 02/16/2018] [Accepted: 02/25/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Chronic infection with hepatitis B virus (HBV) causes liver disease and cirrhosis. It is not clear how treatment of chronic HBV infection affects patient-reported outcomes (PROs). We aimed to assess changes in PROs in patients treated for chronic HBV infection. METHODS We collected and analyzed PRO data from 242 patients with chronic HBV infection (without advanced fibrosis or cirrhosis) enrolled in 2 international phase 2 blinded controlled clinical trials from 2015 through 2017. In these trials, patients were treated with an approved oral antiviral regimen (tenofovir, entecavir, adefovir, lamivudine, or telbivudine) and then randomly assigned to groups given vesatolimod (an oral agonist of Toll-like receptor 7) or placebo. PROs were collected using the Short Form-36, the Chronic Liver Disease Questionnaire, and the Work Productivity and Activity Impairment: Specific Health Problem questionnaires before treatment and during treatment weeks 12, 24, and 48. RESULTS We did not observe significant differences in PROs between patients receiving vesatolimod vs placebo. At baseline, patients with viral suppression (HBV DNA level, <20 IU/mL) had higher PRO scores (by up to +10.6% of a PRO range size). During treatment, there were significant increases in scores for some domains of the Chronic Liver Disease Questionnaire and in General Health scores of Short Form-36 (increases of up to 4.9%; P < .05). Patients with a decrease of at least 2.7 log10 IU/mL in level of HBV DNA had substantially larger increases in PRO scores (P < .05 for 10 of 22 studied PROs). In multivariate analysis, a reduction in viral load was independently associated with increases in PROs (β values up to 1.6% per log10 IU/mL decrease; P < .05). CONCLUSIONS In an analysis of data from phase 2 trials, we associated active treatment of chronic HBV infection with increased PRO scores. These findings support inclusion of PRO end points in assessments of efficacy and safety in clinical trials of treatments for HBV infection.
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Affiliation(s)
- Zobair M Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia.
| | - Maria Stepanova
- Center for Outcomes Research in Liver Disease, Washington, District of Columbia
| | - Harry L A Janssen
- Toronto Centre for Liver Disease, University Health Network, Toronto, Canada
| | - Kosh Agarwal
- Institute of Liver Studies, Kings College Hospital, London, United Kingdom
| | | | - Ed Gane
- Auckland Clinical Studies, Auckland, New Zealand
| | - Naoky Tsai
- Queens Medical Center, University of Hawaii, Honolulu, Hawaii
| | - Issah Younossi
- Center for Outcomes Research in Liver Disease, Washington, District of Columbia
| | - Andrei Racila
- Center for Outcomes Research in Liver Disease, Washington, District of Columbia
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Kmet Lunaček N, Poljak M, Matičič M. Distribution of hepatitis B virus genotypes in Europe and clinical implications: a review. ACTA DERMATOVENEROLOGICA ALPINA PANNONICA ET ADRIATICA 2018. [PMID: 30244264 DOI: 10.15570/actaapa.2018.28] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Khanna R, Verma SK. Pediatric hepatocellular carcinoma. World J Gastroenterol 2018; 24:3980-3999. [PMID: 30254403 PMCID: PMC6148423 DOI: 10.3748/wjg.v24.i35.3980] [Citation(s) in RCA: 88] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2018] [Revised: 07/11/2018] [Accepted: 08/01/2018] [Indexed: 02/06/2023] Open
Abstract
Pediatric hepatocellular carcinoma (HCC) is the second common malignant liver tumor in children after hepatoblastoma. It differs from the adult HCC in the etiological predisposition, biological behavior and lower frequency of cirrhosis. Perinatally acquired hepatitis-B virus, hepatorenal tyrosinemia, progressive familial intrahepatic cholestasis, glycogen storage disease, Alagille’s syndrome and congenital portosystemic shunts are important predisposing factors. Majority of children (87%) are older than 5 years of age. Following mass immunization against hepatitis-B, there has been a drastic fall in the incidence of new cases of pediatric HCC in the Asia-Pacific region. Management is targeted on complete surgical removal either by resection or liver transplantation. There is a trend towards improving survival of children transplanted for HCC beyond Milan criteria. Chemotherapeutic regimens do not offer good results but may be helpful for down-staging of advanced HCC. Surveillance of children with chronic liver diseases with ultrasound and alpha-fetoprotein may be helpful in timely detection, intervention and overall improvement in outcome of HCC.
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Affiliation(s)
- Rajeev Khanna
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi 110070, India
| | - Sanjeev Kumar Verma
- Department of Pediatrics, King George Medical University, Uttar Pradesh 226003, India
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Tufon KA, Anong DN, Meriki HD, Georges TD, Maurice M, Kouanou YS, Bolimo AF, Tony NJ, Kwenti TE, Wung NH, Nkuo-Akenji T. Characterization and assessment of HBV chronically infected patients: Identification of those eligible for treatment in the South West region of Cameroon. PLoS One 2018; 13:e0203312. [PMID: 30183765 PMCID: PMC6124766 DOI: 10.1371/journal.pone.0203312] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2018] [Accepted: 08/18/2018] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND The management of patients with chronic hepatitis B infection is quite complex because it requires an in-depth knowledge of the natural history of the disease. This study was aimed at characterizing HBV infected patients in order to determine the phase of the infection and identify the proportion eligible for treatment using 3 different guidelines. METHODS HBV chronically infected patients (negative for HIV and HCV) were enrolled and the following tests were done for them: ALT, AST, HBV viral load, HBV serologic panel and Full blood count. APRI score was calculated for all patients. These patients were classified into immunotolerant, immune clearance, immune control and immune escape phases of the infection. The WHO and the 2018 AASLD criteria was also used to identify those who need treatment. Patients were clinically examined for signs and symptoms. Questionnaire was administered to all participants to ascertain their treatment status. Statistical analysis was done using SPSS version 21. RESULTS A total of 283 participants (101 females and 182 males) with a mean age of 31.3±8.5 were enrolled. Fifty-two (18.4%) were eligible for treatment (Immune clearance and immune escape phases) and they recorded a significantly higher mean APRI score (0.71±0.51) as compared to those in the immune control and immune tolerant phase (0.43±0.20). Based on WHO and AASLD criteria, 12(4.2%) and 15 (5.3%) were eligible for treatment respectively and these were all subsets of the 52 cases mentioned above. Six (2.1%) and 29 (10.2%) of those identified under the immune control phase were on tenofovir and traditional medication respectively. CONCLUSION Considering treatment for patients in the immune clearance and immune escape phases of the infection can be a reliable strategy to implement in our setting as this may probably tie with considerations from other treatment guidelines. Fifty-two (18.4%) patients were eligible for treatment and none of them were among the 2.1% of patients put on Tenofovir based treatment. This calls for the need for more trained health experts to periodically assess patients, implement an adequate treatment guideline and place the right patients on treatment in Cameroon.
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Affiliation(s)
- Kukwah Anthony Tufon
- Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea, South West Region, Cameroon
- Buea Regional Hospital, Buea, South West Region, Cameroon
| | - Damian Nota Anong
- Department of Biological science, Faculty of Science, University of Bamenda, Bamenda, North West Region, Cameroon
| | - Henry Dilonga Meriki
- Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea, South West Region, Cameroon
- Buea Regional Hospital, Buea, South West Region, Cameroon
- Department of Public health and Hygiene, Faculty of Health science, University of Buea, Buea, South West Region, Cameroon
- BioCollections Worldwide Inc., Miami, FL, United States of America
| | - Teuwafeu Denis Georges
- Buea Regional Hospital, Buea, South West Region, Cameroon
- Department of internal medicine, Faculty of Health science, University of Buea, Buea, South West Region, Cameroon
| | | | | | | | - Nyeke James Tony
- Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea, South West Region, Cameroon
| | - Tebit Emmanuel Kwenti
- Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea, South West Region, Cameroon
- Buea Regional Hospital, Buea, South West Region, Cameroon
- Department of Public health and Hygiene, Faculty of Health science, University of Buea, Buea, South West Region, Cameroon
- Department of Medical Laboratory Science, Faculty of Health science, University of Buea, Buea, South West Region, Cameroon
| | - Ndze Henry Wung
- Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea, South West Region, Cameroon
| | - Theresa Nkuo-Akenji
- Department of Biological science, Faculty of Science, University of Bamenda, Bamenda, North West Region, Cameroon
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Chong LW, Hsu CC, Lee CY, Chou RH, Lin CL, Chang KH, Hsu YC. Association of viral hepatitis and bipolar disorder: a nationwide population-based study. J Transl Med 2018; 16:173. [PMID: 29929549 PMCID: PMC6013873 DOI: 10.1186/s12967-018-1542-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Accepted: 06/07/2018] [Indexed: 12/14/2022] Open
Abstract
Background Bipolar disorder (BD), a type of psychiatric mood disorder, is manifested by chronic and recurrent mood fluctuations. This study aims to determine whether hepatitis B virus (HBV) or hepatitis C virus (HCV) infection is a risk factor for BD. Methods A total of 48,215 patients with newly diagnosed viral hepatitis from 2000 to 2010 were identified and frequency-matched with 192,860 people without hepatitis. Both groups were followed until diagnosis with BD, withdrawal from the national health insurance program, or the end of 2011. Patients with viral hepatitis were grouped into 3 cohorts: HBV infection, HCV infection, and HBV/HCV coinfection. The association between viral hepatitis and BD were examined using Cox proportional hazards regression models. Results The incidence of BD was higher in HBV/HCV coinfection than in the control group, with an adjusted hazard ratio of 2.16 (95% confidence interval 1.06–4.41) when adjusted for sex, age, and comorbidity. After further adjustment, we noted that an age more than 65 years and female may be associated with an increased risk of BD in patients with chronic hepatitis B and C. Conclusion Viral hepatitis may be associated with increased risk of subsequent BD. Electronic supplementary material The online version of this article (10.1186/s12967-018-1542-3) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Lee-Won Chong
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.,School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
| | - Chih-Chao Hsu
- Division of Psychiatry, Taitung Branch, Taipei Veterans General Hospital, Taitung, Taiwan
| | - Chang-Yin Lee
- College of Medicine, The School of Chinese Medicine for Post Baccalaureate, I-Shou University (Yancho Campus), Kaohsiung, Taiwan.,Department of Chinese Medicine, E-DA Hospital, Kaohsiung, Taiwan.,Department of Chinese Medicine, E-DA Cancer Hospital, Kaohsiung, Taiwan
| | - Ruey-Hwang Chou
- Graduate Institute of Biomedical Sciences and Center for Molecular Medicine, China Medical University, Taichung, Taiwan.,Department of Biotechnology, Asia University, Taichung, Taiwan
| | - Cheng-Li Lin
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
| | - Kuang-Hsi Chang
- Department of Medical Research, Tungs' Taichung Metroharbor Hospital, Taichung, Taiwan. .,Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
| | - Yi-Chao Hsu
- Institute of Biomedical Sciences, Mackay Medical College, New Taipei City, Taiwan.
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Li Q, Lu C, Li W, Huang Y, Chen L. The gamma-glutamyl transpeptidase to platelet ratio for non-invasive assessment of liver fibrosis in patients with chronic hepatitis B and non-alcoholic fatty liver disease. Oncotarget 2018; 8:28641-28649. [PMID: 28415736 PMCID: PMC5438679 DOI: 10.18632/oncotarget.16162] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Accepted: 03/04/2017] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND/AIM The gamma-glutamyl transpeptidase-to-platelet ratio (GPR) is a novel serum model, which was reported more accurate than aspartate transaminase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) for diagnosing significant fibrosis and cirrhosis in HBV mono-infection in West Africa. We aimed to evaluate the diagnostic performance of GPR for liver fibrosis in patients with chronic hepatitis B (CHB) and non-alcoholic fatty liver disease (NAFLD). RESULTS Of 131 patients, 41 (31.3%), 20 (15.3%), and 10 (7.6%) were classified as having significant fibrosis, severe fibrosis and cirrhosis, respectively. To predict significant fibrosis, the AUROC of GPR was higher than that of APRI (0.86 vs 0.75, p = 0.001) and FIB-4 (0.86 vs 0.66, p < 0.001). To predict severe fibrosis, the AUROC of GPR was also higher than that of APRI (0.89 vs 0.77, p = 0.002) and FIB-4 (0.89 vs 0.72, p = 0.001). To predict cirrhosis, no difference was found between the AUROC of GPR and that of APRI (0.92 vs 0.86, p = 0.104). MATERIALS AND METHODS 131 patients with CHB-NAFLD were included, and the diagnostic performances of GPR, APRI and FIB-4 were compared by receiver operating characteristic (ROC) curves and the area under ROC curves (AUROCs). CONCLUSIONS The GPR could be used as a non-invasive marker to predict liver fibrosis and cirrhosis in CHB-NAFLD individuals.
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Affiliation(s)
- Qiang Li
- Department of Hepatitis, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.,Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Chuan Lu
- Department of Hepatitis, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
| | - Weixia Li
- Department of Hepatitis, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
| | - Yuxian Huang
- Department of Hepatitis, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.,Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Liang Chen
- Department of Hepatitis, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
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Li Q, Lu C, Li W, Huang Y, Chen L. The gamma-glutamyl transpeptidase-to-albumin ratio predicts significant fibrosis and cirrhosis in chronic hepatitis B patients. J Viral Hepat 2017; 24:1143-1150. [PMID: 28685907 DOI: 10.1111/jvh.12751] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2017] [Accepted: 05/31/2017] [Indexed: 12/20/2022]
Abstract
Background/Aim Simple, inexpensive and clinically available noninvasive liver fibrosis tests are highly needed. We aimed to develop a novel noninvasive index for predicting significant fibrosis and cirrhosis in chronic hepatitis B (CHB) patients. Methods Using liver histology as gold standard, we developed a novel index to predict significant fibrosis and cirrhosis in CHB patients and then compared the diagnostic accuracy of the novel index, aspartate transaminase-to-platelet ratio index (APRI), and fibrosis index based on four factors (FIB-4) in a training set (606 patients) and a validation set (216 patients) from the same patient catchment area. Results Of 606 CHB patients in the training set, 33.2% had significant fibrosis and 11.4% had cirrhosis. In multivariable analysis, gamma-glutamyl transpeptidase (GGT) (OR=1.032, p<0.001) and albumin (OR=0.953, p=0.048) were independent predictors of significant fibrosis. Consequently, a GGT-to-albumin ratio (GAR) was developed. In the training set, the area under the receiver operating characteristic curve (AUROC) of GAR was significantly higher than that of APRI and FIB-4 to predict ≥F2 (0.82, 0.70, and 0.68, respectively), ≥F3 (0.86, 0.76, and 0.75, respectively), and F4 (0.88, 0.75, and 0.73, respectively), respectively. In the validation set, the AUROC of GAR was also better than APRI and FIB-4 for predicting ≥F2 (0.81, 0.63 and 0.61, respectively), ≥F3 (0.88, 0.78, and 0.76, respectively) and F4 (0.92, 0.85, and 0.78, respectively), respectively. Conclusions GAR is a more accurate noninvasive index than APRI and FIB-4 to stage significant fibrosis and cirrhosis in CHB patients and represents a novel noninvasive alternative to liver biopsy.
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Affiliation(s)
- Q Li
- Department of Hepatitis, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.,Department of Infectious Disease, Huashan Hospital, Fudan University, Shanghai, China
| | - C Lu
- Department of Hepatitis, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - W Li
- Department of Hepatitis, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Y Huang
- Department of Hepatitis, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.,Department of Infectious Disease, Huashan Hospital, Fudan University, Shanghai, China
| | - L Chen
- Department of Hepatitis, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
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Chen HL, Wen WH, Chang MH. Management of Pregnant Women and Children: Focusing on Preventing Mother-to-Infant Transmission. J Infect Dis 2017; 216:S785-S791. [PMID: 29156049 DOI: 10.1093/infdis/jix429] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Hepatitis B virus (HBV) immunization has been effectively preventing chronic HBV infection with >90% efficacy in countries with universal neonatal immunization. Perinatal mother-to-infant transmission of HBV remains the major cause of chronic HBV infection despite immunization. Maternal hepatitis B e-antigen (HBeAg) and high viral load have been noted to be the most important risk factors for transmission. In recent years, short-term antiviral therapy for pregnant women in the third trimester has been shown to be highly effective in reducing 90% of vaccine failure in children. It is important to monitor maternal aminotransferase elevations postpartum. Long-term outcome of mothers and children is needed and awaits further investigations. Despite the above-mentioned preventive measures, it is also important to monitor high-risk children at 1 year of age with hepatitis B surface antigen and anti-hepatitis B to identify those with chronic HBV infection. Most of the children with chronic HBV infection were in the immune-tolerant phase. The goals for antiviral treatment in children are to reduce severity of liver injury, achieve HBeAg seroconversion, and prevent development of liver fibrosis and cancer. Studies on antiviral therapy are undergoing to elucidate the optimal indication and drug treatment for children. The ideal future goal of treatment is to eradicate chronic HBV infection globally.
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Affiliation(s)
- Huey-Ling Chen
- Department of Pediatrics, National Taiwan University Children's Hospital and College of Medicine, National Taiwan University, Taipei.,Department of Medical Education and Bioethics, College of Medicine, National Taiwan University, Taipei
| | - Wan-Hsin Wen
- Department of Pediatrics, Cardinal Tien Hospital, New Taipei City, Taiwan.,School of Medicine, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
| | - Mei-Hwei Chang
- Department of Pediatrics, National Taiwan University Children's Hospital and College of Medicine, National Taiwan University, Taipei
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Hu YC, Liu H, Liu XY, Ma LN, Guan YH, Luo X, Ding XC. Value of gamma-glutamyltranspeptidase-to-platelet ratio in diagnosis of hepatic fibrosis in patients with chronic hepatitis B. World J Gastroenterol 2017; 23:7425-7432. [PMID: 29151696 PMCID: PMC5685848 DOI: 10.3748/wjg.v23.i41.7425] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2017] [Revised: 09/14/2017] [Accepted: 09/28/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the value of the gamma-glutamyltraspeptidase (GGT)-to-platelet (PLT) ratio (GPR) in the diagnosis of hepatic fibrosis in patients with chronic hepatitis B (CHB).
METHODS We included 390 untreated CHB patients in this study. The GPR, aspartate aminotransferase (AST)-to-PLT ratio index (APRI), and fibrosis-4 (FIB-4) of all patients were analysed to determine if these parameter were correlated with age, gender, medical history, liver function [total bilirubin (TBil), alanine aminotransferase (ALT), and AST], GGT, PLT count, or hepatic fibrosis stage. The GPR, APRI, and FIB-4, as well as the combination of the GPR and APRI or the GPR and FIB-4 were assessed in different cirrhosis stages using receiver operating characteristic (ROC) curve analysis to evaluate their value in diagnosing hepatic fibrosis in CHB patients.
RESULTS The GPR, APRI, and FIB-4 were not correlated with CHB patients’ age, gender, or disease duration (P > 0.05), but all of these parameters were positively correlated with serum ALT, AST, GGT, and PLT count (P < 0.01). Additionally, the GPR, APRI, and FIB-4 were positively correlated with hepatic fibrosis (P < 0.01); the areas under the ROC curve for the GPR in F1, F2, F3, and F4 stages were 0.723, 0.741, 0.826, and 0.833, respectively, which were significantly higher than the respective values for the FIB-4 and APRI (F1: 0.581, 0.612; F2: 0.706, 0.711; F3: 0.73, 0.751; and F4: 0.799, 0.778). The respective diagnostic cut-off points for each stage were 0.402, 0.448, 0.548, and 0.833, respectively. The diagnostic sensitivity and specificity were, respectively, 88.8% and 87.5% in F1, 72.7% and 89.7% in F2, 81.3% and 98.6% in F3, and 80% and 97.4% in F4 when the GPR and APRI were connected in parallel; 86.6% and 90.2%, 78.4% and 96%, 78.6% and 97.4%, and 73.2% and 97.9%, respectively, when the GPR and APRI were connected in series; 80.2% and 89%, 65% and 89%, 70.3% and 98.5%, and 78.8% and 96.8%, respectively, when the GPR and FIB-4 were connected in parallel; and 83.6% and 87.9%, 76.8% and 96.6%, 72.7% and 98%, and 74.4% and 97.7%, respectively, when the GPR and FIB-4 were connected in series.
CONCLUSION The GPR, as a serum diagnostic index of liver fibrosis, is more accurate, sensitive, and easy to use than the FIB-4 and APRI, and the GPR can significantly improve the sensitivity and specificity of hepatic fibrosis diagnosis in CHB when combined with the FIB-4 or APRI.
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Affiliation(s)
- Yan-Chao Hu
- Department of Infectious Diseases, General Hospital of Ningxia Medical University, Yinchuan 750001, Ningxia Hui Autonomous Region, China
| | - Hao Liu
- Department of Gastroenterology, General Hospital of Ningxia Medical University, Yinchuan 750001, Ningxia Hui Autonomous Region, China
| | - Xiao-Yan Liu
- Department of Infectious Diseases, General Hospital of Ningxia Medical University, Yinchuan 750001, Ningxia Hui Autonomous Region, China
| | - Li-Na Ma
- Department of Infectious Diseases, General Hospital of Ningxia Medical University, Yinchuan 750001, Ningxia Hui Autonomous Region, China
| | - Yu-Hua Guan
- Department of Infectious Diseases, General Hospital of Ningxia Medical University, Yinchuan 750001, Ningxia Hui Autonomous Region, China
| | - Xia Luo
- Department of Infectious Diseases, General Hospital of Ningxia Medical University, Yinchuan 750001, Ningxia Hui Autonomous Region, China
| | - Xiang-Chun Ding
- Department of Infectious Diseases, General Hospital of Ningxia Medical University, Yinchuan 750001, Ningxia Hui Autonomous Region, China
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Association of TNF-Alpha gene polymorphisms and susceptibility to hepatitis B virus infection in Egyptians. Hum Immunol 2017; 78:739-746. [PMID: 29054398 DOI: 10.1016/j.humimm.2017.10.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2017] [Revised: 09/25/2017] [Accepted: 10/16/2017] [Indexed: 12/15/2022]
Abstract
Tumor necrosis factor alpha (TNF-α) is one of the important cytokine in generating an immune response against hepatitis B virus (HBV). Genetic polymorphisms might influence gene transcription, leading to disturbance in cytokine production. We hypothesized that single nucleotide polymorphism (SNPs) in TNF-α gene could affect the pathogenesis of HBV. To test this hypothesis, we investigated the role of TNF-α polymorphism [-863C/A (rs1800630), -308G/A (rs1800629), -376G/A (rs1800750), -857C/T (rs1799724) and +489G/A (rs1800610)] in the susceptibility to chronic hepatitis B (CHB) infection. Polymorphisms of the TNF-α (-863C/A (rs1800630), -308G/A) were analyzed by Polymerase chain reaction sequence specific primer (PCR-SSP) while TNF-α (-376G/A, -857C/T and +489G/A) by PCR-restriction fragment length polymorphism (PCR-RFLP) in 104 patients with CHB and 104 healthy controls. The plasma level of TNF-α was measured using Enzyme-linked immunosorbent assay (ELISA). The study showed a significant increase in the frequency of -863CC, -376GA, -857CC, -857TT and +489GA genotypes and -863C, -376A, -857C, and +489A alleles in CHB patients compared to controls. In addition, CAGCG haplotype had a highest frequency in CHB patients. A strong Linkage Disequilibrium (LD) between TNF-α -863C/A (rs1800630) and -376G/A (D' = 0.7888, r2 = 0.0200); -308G/A and -857C/T (D' = 0.9213, r2 = 0.1770); -308G/A and +489G/A (D' = 0.9088, r2 = 0.1576) was demonstrated. CHB patients had significantly lower levels of TNF-α compared to controls. In conclusion, our preliminary results suggest that -863C/A (rs1800630), -308G/A, -376G/A, and +489G/A of the TNF-α gene may play a role in HBV susceptibility in Egyptians. The significant reduction in TNF-α in CHB patient was independent of any particular genotype/haplotype in TNF-α.
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Ortega-Prieto AM, Dorner M. Immune Evasion Strategies during Chronic Hepatitis B and C Virus Infection. Vaccines (Basel) 2017; 5:E24. [PMID: 28862649 PMCID: PMC5620555 DOI: 10.3390/vaccines5030024] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Revised: 08/25/2017] [Accepted: 08/30/2017] [Indexed: 12/15/2022] Open
Abstract
Both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are a major global healthcare problem with more than 240 million and 70 million infected, respectively. Both viruses persist within the liver and result in progressive liver disease, resulting in liver fibrosis, cirrhosis and hepatocellular carcinoma. Strikingly, this pathogenesis is largely driven by immune responses, unable to clear an established infection, rather than by the viral pathogens themselves. Even though disease progression is very similar in both infections, HBV and HCV have evolved distinct mechanisms, by which they ensure persistence within the host. Whereas HCV utilizes a cloak-and-dagger approach, disguising itself as a lipid-like particle and immediately crippling essential pattern-recognition pathways, HBV has long been considered a "stealth" virus, due to the complete absence of innate immune responses during infection. Recent developments and access to improved model systems, however, revealed that even though it is among the smallest human-tropic viruses, HBV may, in addition to evading host responses, employ subtle immune evasion mechanisms directed at ensuring viral persistence in the absence of host responses. In this review, we compare the different strategies of both viruses to ensure viral persistence by actively interfering with viral recognition and innate immune responses.
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Affiliation(s)
| | - Marcus Dorner
- Section of Virology, Department of Medicine, Imperial College London, London W2 1PG, UK.
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