|
1
|
Wang J, Qiu K, Zhou S, Gan Y, Jiang K, Wang D, Wang H. Risk factors for hepatocellular carcinoma: an umbrella review of systematic review and meta-analysis. Ann Med 2025; 57:2455539. [PMID: 39834076 PMCID: PMC11753015 DOI: 10.1080/07853890.2025.2455539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 01/09/2025] [Accepted: 01/10/2025] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND Numerous meta-analyses have identified various risk factors for hepatocellular carcinoma (HCC), prompting a comprehensive study to synthesize evidence quality and strength. METHODS This umbrella review of meta-analyses was conducted throughout PubMed, EMBASE, Web of Science, and Cochrane Database of Systematic Reviews. Evidence strength was evaluated according to the evidence categories criteria. RESULTS We identified 101 risk factors throughout 175 meta-analyses. 31 risk factors were classified as evidence levels of class I, II, or III. HBV and HCV infections increase HCC risk by 12.5-fold and 11.2-fold, respectively. These risks are moderated by antiviral treatments and virological responses but are exacerbated by higher HBsAg levels, anti-HBc positivity, and co-infection. Smoking, obesity, non-alcoholic fatty liver disease, diabetes, low platelet, elevated liver enzymes and liver fluke infection increase HCC risk, while coffee consumption, a healthy diet, and bariatric surgery lower it. Medications like metformin, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), aspirin, statins, and selective serotonin reuptake inhibitors reduce HCC risk, while acid suppressive agents, particularly proton pump inhibitors, elevate it. Blood type O reduces the risk of HCC, while male gender and older age increase the risk. CONCLUSIONS HBV and HCV are major HCC risk factors, with risk mitigation through antiviral treatments. Lifestyle habits such as smoking and alcohol use significantly increase HCC risk, highlighting the importance of cessation. Certain drugs like aspirin, statins, GLP-1 RAs, and metformin may reduce HCC occurrence, but further research is needed to confirm these effects.
Collapse
Affiliation(s)
- Jie Wang
- Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China
| | - Kaijie Qiu
- Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China
| | - Songsheng Zhou
- Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China
| | - Yichao Gan
- Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China
| | - Keting Jiang
- Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China
| | - Donghuan Wang
- Operations Department, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China
| | - Haibiao Wang
- Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China
| |
Collapse
|
|
2
|
Li M, Tao C, Tang Z, Li K, Wang Y, Zhao C, Tao C, Geng J, Sun K. Ultrasensitive clinical identification of hepatitis B surface antigen (HBsAg) by CRISPR-assisted nanopore sensing. Biosens Bioelectron 2025; 286:117579. [PMID: 40408898 DOI: 10.1016/j.bios.2025.117579] [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: 03/26/2025] [Revised: 05/07/2025] [Accepted: 05/12/2025] [Indexed: 05/25/2025]
Abstract
Hepatitis B virus (HBV) infection is a major global health issue. The underdiagnosis of HBV contributes to the increasing mortality from hepatitis B-related complications. Hepatitis B surface antigen is a biomarker guiding the clinical management of chronic hepatitis B, and its disappearance from the blood is a key sign of functional cure. There is a need for highly sensitive detection methods for early intervention and prevention of disease recurrence. We presented a new CRISPR-assisted nanopore sensing method for ultrasensitive detection of hepatitis B surface antigen. It uses the high specificity and turnover efficiency of the CRISPR-Cas12a system. The system is activated by the competitive binding between hepatitis B surface antigen and its aptamer, followed by restriction enzyme digestion. The products are detected by a nanopore for precise quantification at very low concentrations. The result achieves the limit of quantification (LOQ) of 10 fM, outperforming conventional assays. Clinical validation with patient samples confirms its superiority. This integrated technology is a powerful tool for HBV early diagnosis, treatment monitoring, and disease assessment, and paves the way for nanopore technology in clinical diagnostics.
Collapse
Affiliation(s)
- Minghan Li
- Department of Laboratory Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu 610041, China
| | - Chengyan Tao
- Department of Laboratory Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu 610041, China
| | - Zhuoyun Tang
- Laboratory of Medicine, West China Hospital of Sichuan University, China
| | - Kaiju Li
- Department of Laboratory Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu 610041, China
| | - Yu Wang
- Department of Laboratory Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu 610041, China
| | - Changjian Zhao
- Department of Laboratory Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu 610041, China
| | - Chuanmin Tao
- Department of Laboratory Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu 610041, China.
| | - Jia Geng
- Department of Laboratory Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu 610041, China; Tianfu Jincheng Laboratory, City of Future Medicine, Chengdu 641400, China.
| | - Ke Sun
- Department of Laboratory Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu 610041, China.
| |
Collapse
|
|
3
|
Shan Y, Pang H, Tang Y, Yang N, Wang R, Yang F, Qin B. Altered LY6E and TRIM6 expression in PBMCs correlated with HBsAg clearance and response to Peg-IFN-α treatment in HBeAg-negative chronic hepatitis B patients. Virol J 2025; 22:74. [PMID: 40089754 PMCID: PMC11909810 DOI: 10.1186/s12985-025-02689-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Accepted: 03/01/2025] [Indexed: 03/17/2025] Open
Abstract
BACKGROUND Pegylated interferon alpha (Peg-IFN-α) has the potential to eradicate hepatitis B surface antigen (HBsAg). This study aimed to investigate whether the expression levels of lymphocyte antigen 6 family member E (LY6E) and tripartite motif-containing protein 6 (TRIM6) mRNAs in peripheral blood mononuclear cells (PBMCs) of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV) patients is associated with the response to Peg-IFN-α treatment and HBsAg clearance. METHODS In this prospective study, HBeAg-negative chronic HBV patients treated with Peg-IFN-α were followed for 48 weeks. The participants were classified into two groups, the virological response (VR) group and nonvirological response (NVR) group, according to the changes in HBV DNA and HBsAg levels observed at week 48 of treatment. Furthermore, these patients were divided into a serological response (SR) group and a nonserological response (NSR) group, depending on whether they exhibited a loss of serum HBsAg or evidence of seroconversion. The expression levels of LY6E and TRIM6 mRNAs in PBMCs were evaluated using real-time quantitative PCR with fluorescence detection. The diagnostic performance of LY6E and TRIM6 was assessed by analyzing the receiver operating characteristic (ROC) curve and calculating the area under the ROC curve (AUC). RESULTS After the treatment period, the observed VR and SR rates were 44.64% and 28.57%, respectively. Dynamic changes in LY6E and TRIM6 mRNA levels were significantly different between the VR and NVR groups and between the SR and NSR groups. Multivariate analysis revealed that TRIM6 was independently associated with VR at weeks 12 and 24 of Peg-IFN-α therapy and with SR at week 12; in addition, LY6E was independently associated with VR at week 12 and SR at week 24. At week 24, the area under the curve (AUC) for LY6E in the prediction of VR was 0.6942, and the AUC for the prediction of SR was 0.7766; at week 12, TRIM6 had AUCs of 0.7600 for the prediction of VR and 0.8469 for the prediction of SR. CONCLUSIONS LY6E and TRIM6 are important biomarkers for early therapeutic responses to Peg-IFN-α and HBsAg clearance. TRIAL REGISTRATION Registration number: 2023 - 311. Date of registration: 1 October 2023.
Collapse
Affiliation(s)
- Yiru Shan
- Department of Infectious Diseases, Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Hao Pang
- Department of Infectious Diseases, Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yao Tang
- Department of Infectious Diseases, Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Na Yang
- Central Laboratory, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Rui Wang
- Central Laboratory, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Fan Yang
- Department of Infectious Diseases, Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
| | - Bo Qin
- Department of Infectious Diseases, Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
| |
Collapse
|
|
4
|
Qiu Z, Xu Y, Qi W, Shen J, Wen T, Li C. Tenofovir vs Entecavir on the Prognosis of Patients With Hepatitis B Virus-Related Hepatocellular Carcinoma After Liver Resection: The Role of HBsAg Levels. Clin Transl Gastroenterol 2025; 16:e00814. [PMID: 39791573 PMCID: PMC11932590 DOI: 10.14309/ctg.0000000000000814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Accepted: 12/20/2024] [Indexed: 01/12/2025] Open
Abstract
INTRODUCTION Our study aimed to explore whether hepatitis B surface antigen (HBsAg) levels affected the role of nucleot(s)ide analog treatment (entecavir [ETV] and tenofovir disoproxil fumarate [TDF]) in improving the prognosis of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after liver resection. METHODS A total of 865 patients with HBV-related HCC after hepatectomy treated with TDF or ETV were included in our study. Patients were divided into the high HBsAg cohort (n = 681) and the low HBsAg cohort (n = 184). Propensity score matching (PSM) analysis was used to reduce the impact of potential confounding factors. Kaplan-Meier method and competing risk analysis were used to compare the survival outcomes. RESULTS In the high HBsAg cohort, patients in the TDF group had better recurrence-free survival (RFS) and overall survival (OS) compared with patients in the ETV group both before (RFS: P < 0.001; OS: P < 0.001) and after (RFS: P = 0.005; OS: P = 0.035) PSM. TDF treatment was a favorable factor independently associated with RFS (hazard ratio: 0.58, 95% confidence interval: 0.45-0.75, P < 0.001) and OS (hazard ratio: 0.43, 95% confidence interval: 0.28-0.66, P < 0.001). In the low HBsAg cohort, no difference was observed in RFS and OS between the TDF group and the ETV group both before (RFS: P = 0.140; OS: P = 0.640) and after (RFS: P = 0.480; OS: P = 0.920) PSM. TDF treatment remained superiority after controlling for competing events by competing risk analysis in the high HBsAg cohort. DISCUSSION TDF treatment was superior to ETV treatment in improving RFS and OS of HBV-related HCC patients with high HBsAg level after liver resection. Even after controlling for survival competing events, the advantage of TDF treatment remained. Our findings may better help clinicians to assign individualized antiviral regimens to patients with HBV-related HCC after liver resection.
Collapse
MESH Headings
- Humans
- Carcinoma, Hepatocellular/virology
- Carcinoma, Hepatocellular/mortality
- Carcinoma, Hepatocellular/surgery
- Carcinoma, Hepatocellular/blood
- Carcinoma, Hepatocellular/pathology
- Male
- Female
- Liver Neoplasms/virology
- Liver Neoplasms/mortality
- Liver Neoplasms/surgery
- Liver Neoplasms/blood
- Liver Neoplasms/pathology
- Hepatitis B Surface Antigens/blood
- Middle Aged
- Tenofovir/therapeutic use
- Hepatectomy
- Antiviral Agents/therapeutic use
- Guanine/analogs & derivatives
- Guanine/therapeutic use
- Retrospective Studies
- Prognosis
- Hepatitis B virus/isolation & purification
- Hepatitis B virus/immunology
- Aged
- Neoplasm Recurrence, Local/epidemiology
- Neoplasm Recurrence, Local/prevention & control
- Hepatitis B, Chronic/drug therapy
- Hepatitis B, Chronic/complications
- Hepatitis B, Chronic/mortality
- Propensity Score
- Adult
- Kaplan-Meier Estimate
- Hepatitis B/drug therapy
- Hepatitis B/complications
Collapse
Affiliation(s)
- Zhancheng Qiu
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Yueqing Xu
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Weili Qi
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Junyi Shen
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Tianfu Wen
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Chuan Li
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| |
Collapse
|
|
5
|
Kim KS, Iwamoto M, Kitagawa K, Park H, Hayashi S, Tsukuda S, Matsui T, Atsukawa M, Matsuura K, Chuaypen N, Tangkijvanich P, Allweiss L, Nishiyama T, Nakamura N, Fujita Y, Kawakami E, Nakaoka S, Muramatsu M, Aihara K, Wakita T, Perelson AS, Dandri M, Watashi K, Iwami S, Tanaka Y. Prediction of cccDNA dynamics in hepatitis B patients by a combination of serum surrogate markers. PLoS Comput Biol 2025; 21:e1012615. [PMID: 39787253 PMCID: PMC11753647 DOI: 10.1371/journal.pcbi.1012615] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 01/22/2025] [Accepted: 11/04/2024] [Indexed: 01/12/2025] Open
Abstract
Quantification of intrahepatic covalently closed circular DNA (cccDNA) is a key for evaluating an elimination of hepatitis B virus (HBV) in infected patients. However, quantifying cccDNA requires invasive methods such as a liver biopsy, which makes it impractical to access the dynamics of cccDNA in patients. Although HBV RNA and HBV core-related antigens (HBcrAg) have been proposed as surrogate markers for evaluating cccDNA activity, they do not necessarily estimate the amount of cccDNA. Here, we employed a recently developed multiscale mathematical model describing intra- and intercellular viral propagation and applied it in HBV-infected patients under treatment. We developed a model that can predict intracellular HBV dynamics by use of extracellular viral markers, including HBsAg, HBV DNA, and HBcrAg in peripheral blood. Importantly, the model prediction of the amount of cccDNA in patients over time was confirmed to be well correlated with the data for quantified cccDNA by paired liver biopsy. Thus, our method combining classic and emerging surrogate markers enables us to predict the decay dynamics of cccDNA in patients undergoing treatment.
Collapse
Affiliation(s)
- Kwang Su Kim
- interdisciplinary Biology Laboratory (iBLab), Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya, Japan
- Department of Scientific Computing, Pukyong National University, Busan, South Korea
| | - Masashi Iwamoto
- interdisciplinary Biology Laboratory (iBLab), Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya, Japan
- Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
| | - Kosaku Kitagawa
- interdisciplinary Biology Laboratory (iBLab), Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya, Japan
| | - Hyeongki Park
- interdisciplinary Biology Laboratory (iBLab), Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya, Japan
| | - Sanae Hayashi
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Senko Tsukuda
- Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - Takeshi Matsui
- Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Masanori Atsukawa
- Department of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Kentaro Matsuura
- Department of Gastroenterology and Metabolism, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan
| | - Natthaya Chuaypen
- Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Pisit Tangkijvanich
- Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Lena Allweiss
- Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel-Riems partner sites, Germany
| | - Takara Nishiyama
- interdisciplinary Biology Laboratory (iBLab), Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya, Japan
| | - Naotoshi Nakamura
- interdisciplinary Biology Laboratory (iBLab), Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya, Japan
| | - Yasuhisa Fujita
- interdisciplinary Biology Laboratory (iBLab), Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya, Japan
| | - Eiryo Kawakami
- Artificial Intelligence Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
- Medical Sciences Innovation Hub Program; RIKEN, Yokohama, Kanagawa, Japan
| | - Shinji Nakaoka
- Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan
| | - Masamichi Muramatsu
- Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
| | - Kazuyuki Aihara
- International Research Center for Neurointelligence, The University of Tokyo Institutes for Advanced Study, The University of Tokyo, Tokyo, Japan
| | - Takaji Wakita
- Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
| | - Alan S. Perelson
- Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America
| | - Maura Dandri
- Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Koichi Watashi
- Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
- Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo, Japan
- Department of Applied Biological Sciences, Faculty of Science and Technology, Tokyo University of Sciences, Chiba, Japan
| | - Shingo Iwami
- interdisciplinary Biology Laboratory (iBLab), Division of Natural Science, Graduate School of Science, Nagoya University, Nagoya, Japan
- International Research Center for Neurointelligence, The University of Tokyo Institutes for Advanced Study, The University of Tokyo, Tokyo, Japan
- Institute of Mathematics for Industry, Kyushu University,; Fukuoka, Japan
- Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto, Japan
- NEXT-Ganken Program, Japanese Foundation for Cancer Research (JFCR), Tokyo, Japan
- Interdisciplinary Theoretical and Mathematical Sciences (iTHEMS), RIKEN, Wako, Japan
- Science Groove Inc., Fukuoka, Japan
| | - Yasuhito Tanaka
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| |
Collapse
|
|
6
|
Nguyen UD, Le Do Q, Vu QAN, Trieu NT, Dao TT, Van Le N, Nguyen ST, Hoang TT, Nguyen CT, Nguyen TH, Van Nguyen D, Ho TH. Selective detection of HBV pre-genomic RNA in chronic hepatitis B patients using a novel RT-PCR assay. Clin Exp Med 2023; 23:5281-5289. [PMID: 37572154 DOI: 10.1007/s10238-023-01162-6] [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: 04/25/2023] [Accepted: 07/31/2023] [Indexed: 08/14/2023]
Abstract
In chronic hepatitis B (CHB) patients, quantification of HBV pgRNA in plasma has the potential to provide information on disease prognosis and liver injury or histopathology. However, current methods for detecting HBV pgRNA present technical difficulties due to the co-existence of HBV DNA in plasma samples. We have successfully established a novel one-step RT-PCR assay that allows selective quantification of HBV pgRNA. Two cohorts of participants were recruited for assay validation, including treatment-naïve patients with CHB and HBeAg-positive CHB patients who were treated with Tenofovir and monitored for 6 months to assess the predictive value of baseline HBV RNA for HBeAg seroclearance. Statistical analysis was performed using MedCalc version 20.019 software. The novel selective one-step RT-PCR assay for detecting HBV pgRNA was validated with a limit of detection of 100 copies/mL. The assay was able to selectively measure HBV pgRNA even in the presence of excess HBV rcDNA. In treatment-naïve CHB patients, HBV pgRNA levels were significantly lower than HBV DNA concentration. Serum HBV DNA levels and HBeAg status were positively associated with HBV pgRNA. Baseline serum HBV pgRNA levels were found to be strong predictors of HBeAg seroclearance after 6 months of Tenofovir treatment. The study presents a novel RT-PCR assay that allows accurate measurement of plasma HBV pgRNA in chronic hepatitis B patients, even in the presence of excess HBV DNA. The assay is highly selective and represents a significant advancement with potential for further breakthroughs in understanding the clinical significance of HBV pgRNA.
Collapse
Affiliation(s)
- Ung Dinh Nguyen
- Department of Genomics and Cytogenetics, Institute of Biomedicine and Pharmacy (IBP), Vietnam Military Medical University, Hanoi, Vietnam
| | - Quyen Le Do
- Department of Infectious Disease, 103 Military Hospital, Vietnam Military Medical University, Hanoi, Vietnam
| | - Quynh Anh Nguyen Vu
- Department of Genomics and Cytogenetics, Institute of Biomedicine and Pharmacy (IBP), Vietnam Military Medical University, Hanoi, Vietnam
| | - Nguyet Thi Trieu
- Department of Genomics and Cytogenetics, Institute of Biomedicine and Pharmacy (IBP), Vietnam Military Medical University, Hanoi, Vietnam
| | - Trang Thuy Dao
- Department of Genomics and Cytogenetics, Institute of Biomedicine and Pharmacy (IBP), Vietnam Military Medical University, Hanoi, Vietnam
| | - Nam Van Le
- Department of Infectious Disease, 103 Military Hospital, Vietnam Military Medical University, Hanoi, Vietnam
| | - Son Thai Nguyen
- Department of Microbiology, 103 Military Hospital, Vietnam Military Medical University, Hanoi, Vietnam
- Medical Testing Center, Medlatec Group, Hanoi, Vietnam
| | - Tuyen Tien Hoang
- Department of Infectious Disease, 103 Military Hospital, Vietnam Military Medical University, Hanoi, Vietnam
| | - Chinh Trong Nguyen
- Department of Infectious Disease, 103 Military Hospital, Vietnam Military Medical University, Hanoi, Vietnam
| | - Thang Hong Nguyen
- Outpatient Department, 103 Military Hospital, Vietnam Military Medical University, Hanoi, Vietnam
| | - Dien Van Nguyen
- Department of Infectious Disease, 103 Military Hospital, Vietnam Military Medical University, Hanoi, Vietnam
- Systems Immunity Research Institute, School of Medicine, Cardiff University, Cardiff, UK
| | - Tho Huu Ho
- Department of Genomics and Cytogenetics, Institute of Biomedicine and Pharmacy (IBP), Vietnam Military Medical University, Hanoi, Vietnam.
- Department of Microbiology, 103 Military Hospital, Vietnam Military Medical University, Hanoi, Vietnam.
| |
Collapse
|
|
7
|
Zhang L, Yang L, Gao Y, Bi X, Lin Y, Deng W, Jiang T, Lu Y, Hao H, Wan G, Yi W, Xie Y, Li M. Nomogram for evaluating obvious liver inflammation in treatment-naïve HBeAg positive chronic hepatitis B virus infection patients with normal ALT. Virulence 2023; 14:2158710. [PMID: 36600180 PMCID: PMC9828634 DOI: 10.1080/21505594.2022.2158710] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Accepted: 12/11/2022] [Indexed: 01/06/2023] Open
Abstract
The purpose of this study was to develop an effective and non-invasive nomogram for evaluating liver obvious inflammation in untreated HBeAg positive patients with chronic hepatitis B virus (HBV) infection. A nomogram was established on a model cohort of 292 treatment-naïve HBeAg positive patients with normal alanine aminotransferase (ALT ≤40 U/L) at Beijing Ditan Hospital from January 2008 to March 2018. Then the nomogram was prospectively validated in a cohort of 88 patients from July 2019 to May 2021. Calibration curves and Concordance index were used to evaluate the accuracy of prediction and identification performance of the model. In untreated HBeAg positive chronic hepatitis B virus infection patients with normal ALT, the formula for predicting liver inflammation was Logit (P) =-0.91-0.41×log10 (qHBeAg)+0.11×AST-0.01×PLT. The nomogram had C-index of 0.751 (95% CI, 0.688-0.815), indicating a good consistency between prediction and real observation on the model cohort. The validation cohort confirmed its good performance. In this study, liver inflammation nomograms based on HBeAg, AST, and PLT were established and verified in treatment-naïve HBeAg positive chronic HBV patients with normal ALT.
Collapse
Affiliation(s)
- Lu Zhang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Liu Yang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yuanjiao Gao
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xiaoyue Bi
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yanjie Lin
- Department of Medical Record Statistics, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Wen Deng
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Tingting Jiang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yao Lu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Hongxiao Hao
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Gang Wan
- Department of Gynecology and Obstetrics, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Wei Yi
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
| | - Yao Xie
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Department of Medical Record Statistics, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Minghui Li
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Department of Medical Record Statistics, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| |
Collapse
|
|
8
|
Kobayakawa T, Amano M, Nakayama M, Tsuji K, Ishii T, Miura Y, Shinohara K, Yamamoto K, Matsuoka M, Tamamura H. Development of anti-HBV agents targeting HBV capsid proteins. RSC Med Chem 2023; 14:1973-1980. [PMID: 37859721 PMCID: PMC10583812 DOI: 10.1039/d3md00258f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Accepted: 07/31/2023] [Indexed: 10/21/2023] Open
Abstract
Hepatitis B is a viral hepatitis, which is caused by infection of hepatitis B virus (HBV). This disease progresses to chronic hepatitis, cirrhosis and liver cancer. To treat hepatitis B, exclusion of virus and covalently closed circular DNA (cccDNA) that is formed in hepatocyte nucleus is necessary. A hepatitis B capsid protein (HBc) is an indispensable protein, which forms the capsid that encapsulates viral DNA. Since HBc is correlated to the transcriptional regulation of cccDNA, this protein would be an attractive target for complete cure of hepatitis B. By in silico screening of a library of compounds, a small compound, Cpd4 (1), which binds to a hydrophobic cavity located in the inner pocket on the tetramer interface of HBc proteins, was identified. In anti-HBV assays, this synthetic compound, Cpd4 (1) decreased the amount of HBV core related antigen (HBcrAg), which has been correlated with the proliferation of HBV, and decreased the amount of HBV surface antigen (HBsAg), which is correlated with the amount of cccDNA. Based on Cpd4 (1) as a lead compound, 20 derivatives of 1 were designed and synthesized and their structure-activity relationships were examined. As a result, specific interactions between each compound and amino acid residues of the target protein appeared to be unimportant but the shape/size of compounds which can bind to the hydrophobic cavity might be important in the expression of high anti-HBV activity, and a more potent derivative, TKB-HBV-CA-001 (3b), was discovered. These results will be useful in the development of novel anti-HBV agents for a complete cure of hepatitis B.
Collapse
Affiliation(s)
- Takuya Kobayakawa
- Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU) 2-3-10 Kandasurugadai, Chiyoda-ku Tokyo 101-0062 Japan
| | - Masayuki Amano
- Department of Clinical Retrovirology, Joint Research Center for Human Retrovirus Infection, Kumamoto and Kagoshima Universities Kumamoto 860-0811 Japan
- Department of Hematology, Rheumatology, and Infectious Diseases, Faculty of Life Sciences, Kumamoto University Kumamoto 860-8556 Japan
| | - Miyuki Nakayama
- Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU) 2-3-10 Kandasurugadai, Chiyoda-ku Tokyo 101-0062 Japan
| | - Kohei Tsuji
- Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU) 2-3-10 Kandasurugadai, Chiyoda-ku Tokyo 101-0062 Japan
| | - Takahiro Ishii
- Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU) 2-3-10 Kandasurugadai, Chiyoda-ku Tokyo 101-0062 Japan
| | - Yutaro Miura
- Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU) 2-3-10 Kandasurugadai, Chiyoda-ku Tokyo 101-0062 Japan
| | - Kouki Shinohara
- Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU) 2-3-10 Kandasurugadai, Chiyoda-ku Tokyo 101-0062 Japan
| | - Kenichi Yamamoto
- Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU) 2-3-10 Kandasurugadai, Chiyoda-ku Tokyo 101-0062 Japan
| | - Masao Matsuoka
- Department of Hematology, Rheumatology, and Infectious Diseases, Faculty of Life Sciences, Kumamoto University Kumamoto 860-8556 Japan
| | - Hirokazu Tamamura
- Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU) 2-3-10 Kandasurugadai, Chiyoda-ku Tokyo 101-0062 Japan
| |
Collapse
|
|
9
|
Kim SR, Kim SK. Hepatocellular Carcinoma and Hepatitis: Advanced Diagnosis and Management with a Focus on the Prevention of Hepatitis B-Related Hepatocellular Carcinoma. Diagnostics (Basel) 2023; 13:3212. [PMID: 37892033 PMCID: PMC10605503 DOI: 10.3390/diagnostics13203212] [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: 08/29/2023] [Revised: 10/06/2023] [Accepted: 10/10/2023] [Indexed: 10/29/2023] Open
Abstract
Though the world-wide hepatitis B virus (HBV) vaccination program has been well completed for almost thirty years in many nations, almost HBV-related hepatocellular carcinoma (HCC) occurs in unvaccinated middle-aged and elderly adults. Apparently, treating 80% of qualified subjects could decrease HBV-related mortality by 65% in a short period. Nevertheless, globally, only 2.2% of CHB patients undergo antiviral therapy. The HBV markers related to HCC occurrence and prevention are as follows: the HCC risk is the highest at a baseline of HBV DNA of 6-7 log copies/mL, and it is the lowest at a baseline of an HBV DNA level of >8 log copies/mL and ≤4 log copies/mL (parabolic, and not linear pattern). The titer of an HBV core-related antigen (HBcrAg) reflecting the amount of HBV covalently closed circular DNA (ccc DNA) in the liver is related to HCC occurrence. The seroclearance of HBs antigen (HBsAg) is more crucial than HBV DNA negativity for the prevention of HCC. In terms of the secondary prevention of hepatitis B-related HCC involving antiviral therapies with nucleos(t)ide analogues (NAs), unsolved issues include the definition of the immune-tolerant phase; the optimal time for starting antiviral therapies with NAs; the limits of increased aminotransferase (ALT) levels as criteria for therapy in CHB patients; the normalization of ALT levels with NAs and the relation to the risk of HCC; and the relation between serum HBV levels and the risk of HCC. Moreover, the first-line therapy with NAs including entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) remains to be clarified. Discussed here, therefore, are the recent findings of HBV markers related to HCC occurrence and prevention, unsolved issues, and the current secondary antiviral therapy for the prevention of HBV-related HCC.
Collapse
Affiliation(s)
| | - Soo Ki Kim
- Department of Gastroenterology, Kobe Asahi Hospital, Kobe 653-0801, Japan;
| |
Collapse
|
|
10
|
He P, Zhang P, Fang Y, Han N, Yang W, Xia Z, Zhu Y, Zhang Z, Shen J. The role of HBV cccDNA in occult hepatitis B virus infection. Mol Cell Biochem 2023; 478:2297-2307. [PMID: 36735210 DOI: 10.1007/s11010-023-04660-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Accepted: 01/09/2023] [Indexed: 02/04/2023]
Abstract
Occult hepatitis B virus (HBV) infection (OBI) refers to the presence of replication-competent HBV DNA in the liver, with or without HBV DNA in the blood, in individuals who tested negative for HBV surface antigen (HBsAg). In this peculiar phase of HBV infection, the covalently closed circular DNA (cccDNA) is in a low state of replication. Several advances have been made toward clarifying the mechanisms involved in such a suppression of viral activity, which seems to be mainly related to the host's immune control and epigenetic factors. Although the underlying mechanisms describing the genesis of OBI are not completely known, the presence of viral cccDNA, which remains in a low state of replication due to the host's strong immune suppression of HBV replication and gene expression, appears to be the causative factor. Through this review, we have provided an updated account on the role of HBV cccDNA in regulating OBI. We have comprehensively described the HBV cell cycle, cccDNA kinetics, current regulatory mechanisms, and the therapeutic methods of cccDNA in OBI-related diseases.
Collapse
Affiliation(s)
- Pei He
- Department of Laboratory Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230012, People's Republic of China
- Anhui Public Health Clinical Center, Hefei, 230012, People's Republic of China
- Department of Infectious Diseases, The Second Hospital of Anhui Medical University, Hefei, China
| | - Peixin Zhang
- Department of Infectious Diseases, The Second Hospital of Anhui Medical University, Hefei, China
| | - Yaping Fang
- Department of Clinical Laboratory, The Second Hospital of Anhui Medical University, Hefei, China
| | - Ning Han
- Department of Clinical Laboratory, The Second Hospital of Anhui Medical University, Hefei, China
| | - Wensu Yang
- Department of Laboratory Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230012, People's Republic of China
- Anhui Public Health Clinical Center, Hefei, 230012, People's Republic of China
| | - Zhaoxin Xia
- Department of Laboratory Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230012, People's Republic of China
- Anhui Public Health Clinical Center, Hefei, 230012, People's Republic of China
| | - Yi Zhu
- Department of Laboratory Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230012, People's Republic of China
- Anhui Public Health Clinical Center, Hefei, 230012, People's Republic of China
| | - Zhenhua Zhang
- Department of Infectious Diseases, The Second Hospital of Anhui Medical University, Hefei, China.
| | - Jilu Shen
- Department of Laboratory Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230012, People's Republic of China.
- Anhui Public Health Clinical Center, Hefei, 230012, People's Republic of China.
| |
Collapse
|
|
11
|
Hui KY, Fung J, Cheung KS, Mak LY, Seto WK, Yuen MF. Long-term Hepatitis B Surface Antigen Profile and Seroclearance after Severe Acute Flares of Chronic Hepatitis B. Gut Liver 2023; 17:280-287. [PMID: 36317514 PMCID: PMC10018308 DOI: 10.5009/gnl220122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 06/02/2022] [Accepted: 06/21/2022] [Indexed: 11/07/2022] Open
Abstract
Background/Aims Hepatitis B surface antigen (HBsAg) seroclearance remains uncommon in chronic hepatitis B (CHB) infection. During acute flares of CHB (AFOCHB), alanine aminotransferase elevation reflects a mounting immune response toward viral clearance. We hypothesized that severe AFOCHB is associated with a greater quantitative HBsAg (qHBsAg) decline and HBsAg seroclearance rate. Methods A total of 75 patients with severe AFOCHB with alanine aminotransferase 10× the upper limit of normal were matched to a control group by age and sex in a 1:2 ratio. qHBsAg levels were measured at the time of flare and annually (for both cases and controls) until the last follow-up. Results The median follow-up times for patients with severe AFOCHB and controls were 8.8 and 10.5 years, respectively. The cumulative rate of HBsAg seroclearance was higher in the severe AFOCHB group than in the control group (11.8% vs 5.0%, p=0.04) despite the former group having a trend of a higher baseline median qHBsAg (3,127 IU/mL vs 1,178 IU/mL, p=0.076). Compared with the control group, the severe AFOCHB group had a greater annual qHBsAg reduction (-242.4 IU/mL/yr vs -47.3 IU/mL/yr, p=0.002). Increasing age (p=0.049), lower baseline qHBsAg (p=0.002), and severe AFOCHB (p=0.014) were independently associated with HBsAg seroclearance. However, the cumulative rate of hepatocellular carcinoma was significantly higher in the severe AFOCHB group than in the control group (15.8% vs 1.9%, p<0.001). Conclusions Severe AFOCHB was associated with a greater incidence of HBsAg seroclearance and qHBsAg decline. However, it was associated with a higher incidence of hepatocellular carcinoma.
Collapse
Affiliation(s)
- Ka-Yin Hui
- Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China
| | - James Fung
- Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China
| | - Ka-Shing Cheung
- Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China.,Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Lung-Yi Mak
- Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China.,State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong SAR, China
| | - Wai-Kay Seto
- Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China.,Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.,State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong SAR, China
| | - Man-Fung Yuen
- Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China.,State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong SAR, China
| |
Collapse
|
|
12
|
Sun F, Xia W, Ouyang Y. Research progress on detection methods for hepatitis B virus covalently closed circular DNA. J Viral Hepat 2023; 30:366-373. [PMID: 36751941 DOI: 10.1111/jvh.13817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Accepted: 02/04/2023] [Indexed: 02/09/2023]
Abstract
Hepatitis B virus (HBV) infection remains a serious global public health problem, and HBV covalently closed circular DNA (cccDNA) in the nucleus of infected cells cannot be eliminated by current treatments and is a major factor in the persistence and recurrence of hepatitis B. Efficient and scientific detection methods are important for clinical monitoring of cccDNA and targeted drug development. Western blotting is the gold standard for the quantitative detection of cccDNA, but it is time-consuming and complex. In recent years, new detection technologies have been continuously updated. There are new developments and breakthroughs in both next-generation polymerase chain reaction (PCR) and non-PCR methods such as in situ hybridization. Some HBV-related markers (such as hepatitis B core-related antigen) have also been shown to be closely related to cccDNA, and they can be used as surrogate markers to indirectly reflect cccDNA content. In this paper, the main detection methods of cccDNA and their improvements are reviewed, the advantages and limitations of these methods are analysed and summarized, and future development directions are proposed.
Collapse
Affiliation(s)
- Fenglan Sun
- Department of Laboratory Medicine, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, China
| | - Wei Xia
- Department of Laboratory Medicine, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, China
| | - Yaoling Ouyang
- Department of Laboratory Medicine, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, China
| |
Collapse
|
|
13
|
Hu M, Liao G, Wei S, Qian Z, Chen H, Xia M, Xie Q, Peng J. Effective Analysis of Antiviral Treatment in Patients with HBeAg-Seropositive Chronic Hepatitis B with ALT < 2 Upper Limits of Normal: A Multi-center Retrospective Cohort Study. Infect Dis Ther 2023; 12:637-647. [PMID: 36633817 PMCID: PMC9925662 DOI: 10.1007/s40121-022-00757-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Accepted: 12/22/2022] [Indexed: 01/13/2023] Open
Abstract
INTRODUCTION Although the indications for antiviral therapy for patients with chronic hepatitis B have been gradually expanded in different guidelines, antiviral treatment efficacy remains unclear among HBeAg-seropositive patients with alanine aminotransferase (ALT) < 2 upper limits of normal (ULN). This study aimed to evaluate the efficacy of antiviral therapy for these patients. METHODS In total, 102 treatment-naive patients who were HBeAg seropositive with ALT < 2 ULN and had received nucleotide analogs were included, and their clinical data were retrospectively analyzed. RESULTS After 96-week treatment, 84.3% (n = 86), 26.5% (n = 27) and 20.6% (n = 21) patients achieved virological response, HBeAg seroclearance and HBeAg seroconversion, respectively. Logistic regression analysis revealed that baseline AST (odds ratio [OR] = 1.069, 95% confidence interval [CI] 1.014-1.127, p = 0.014), serum HBV DNA (OR = 0.540, 95% CI 0.309-0.946, p = 0.031) and quantitative HBsAg levels (OR = 0.147, 95% CI 0.036-0.597, p = 0.007) were independent factors for virological response. At baseline, HBsAg < 4.63 log10 IU/ml was identified as a strong predictor for the 96-week virological response, with a concordance rate of 0.902. Moreover, the levels of liver stiffness values (8.30 ± 3.86 vs. 6.17 ± 1.91, p < 0.001) at week 96 had significantly declined compared to baseline. CONCLUSION Nucleotide analog treatment effectively suppressed HBV DNA in patients with HBeAg-seropositive chronic hepatitis B with ALT < 2 × ULN and greatly improved liver fibrosis. The study also found that HBsAg < 4.63 log10 IU/ml was a strong predictor of the virological response.
Collapse
Affiliation(s)
- Meixin Hu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Guichan Liao
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Sufang Wei
- Department of Infectious Diseases, Shunde Hospital, Southern Medical University, Foshan, China
| | - Zhe Qian
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Hongjie Chen
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Muye Xia
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Qiuli Xie
- Department of Infectious Diseases, Shunde Hospital, Southern Medical University, Foshan, China
| | - Jie Peng
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
| |
Collapse
|
|
14
|
Xie Y, Zhu H, Guo Y, Ma Z, Qi X, Yang F, Mao R, Zhang J. Reduction of Hepatitis B Surface Antigen May Be More Significant in PEGylated Interferon-Alpha Therapy Combined with Nucleotide Analogues than Combined with Nucleoside Analogues in Chronic Hepatitis B Patients: A Propensity Score Matching Study. Can J Gastroenterol Hepatol 2022; 2022:4325352. [PMID: 36531834 PMCID: PMC9750779 DOI: 10.1155/2022/4325352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 11/09/2022] [Accepted: 11/28/2022] [Indexed: 12/12/2022] Open
Abstract
Background Nucleotide analogues (NTs) monotherapy may have a more significant effect on reducing hepatitis B surface antigen (HBsAg) than nucleoside analogues (NSs) due to their immunomodulatory function. However, this superiority remains unknown when combined with PEGylated interferon α (PegIFNα). Therefore, this study aimed to explore whether NTs have more significant antiviral effects than NSs in combination therapy with PegIFNα. Methods Chronic hepatitis B (CHB) patients treated with PegIFNα plus nucleos(t)ide analogues (NAs) were retrospectively recruited. Efficacy and the predictors of hepatitis B surface antigen (HBsAg) reduction >1 log10 IU/mL after 48 weeks were analyzed. Results A total of 95 patients were included and divided into the PegIFNα + NTs group and the PegIFNα + NSs group. Propensity score matching (PSM) was performed. The PegIFNα + NTs group had a greater reduction of HBsAg (-3.52 vs. -2.33 log10 IU/mL, P=0.032) and a higher proportion of patients with HBsAg reduction >1 log10 IU/mL (100.0% vs. 72.2%, P=0.003) even after PSM. However, HBsAg and hepatitis B e-antigen (HBeAg) loss rates, HBeAg seroconversion rates, degree of HBeAg and hepatitis B virus (HBV) DNA decline, HBV DNA undetectable rates, and alanine aminotransferase (ALT) normalization rates showed no significant differences. Subgroup analyses showed the difference in the reduction of HBsAg was particularly evident in HBeAg-positive and the "add-on" subgroups. PegIFNα plus NTs (OR = 36.667, 95% CI = 3.837-350.384) was an independent predictor for HBsAg reduction >1 log10 IU/mL after 48 weeks. Conclusion This study suggests that PegIFNα plus NTs may lead to more HBsAg reduction, especially in HBeAg-positive and "add-on" patients.
Collapse
Affiliation(s)
- Yiran Xie
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Haoxiang Zhu
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Yifei Guo
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Zhenxuan Ma
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Xun Qi
- Shanghai Public Health Center of Fudan University, Shanghai, China
| | - Feifei Yang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Richeng Mao
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Jiming Zhang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
- Department of Infectious Diseases, Jing'An Branch of Huashan Hospital, Fudan University, Shanghai, China
| |
Collapse
|
|
15
|
Ceesay A, Bouherrou K, Tan BK, Lemoine M, Ndow G, Testoni B, Chemin I. Viral Diagnosis of Hepatitis B and Delta: What We Know and What Is Still Required? Specific Focus on Low- and Middle-Income Countries. Microorganisms 2022; 10:2096. [PMID: 36363693 PMCID: PMC9694472 DOI: 10.3390/microorganisms10112096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Revised: 10/11/2022] [Accepted: 10/18/2022] [Indexed: 01/25/2023] Open
Abstract
To achieve the World Health Organization's (WHO) goals of eradicating viral hepatitis globally by 2030, the regional prevalence and epidemiology of hepatitis B virus (HBV) and hepatitis delta virus (HDV) coinfection must be known in order to implement preventiveon and treatment strategies. HBV/HDV coinfection is considered the most severe form of vira l hepatitis due to it's rapid progression towards cirrhosis, hepatocellular carcinoma, and liver-related death. The role of simplified diagnosticsis tools for screening and monitoring HBV/HDV-coinfected patients is crucial. Many sophisticated tools for diagnoses have been developed for detection of HBV alone as well as HBV/HDV coinfection. However, these advanced techniques are not widely available in low-income countries and there is no standardization for HDV detection assays, which are used for monitoring the response to antiviral therapy. More accessible and affordable alternative methods, such as rapid diagnostic tests (RDTs), are being developed and validated for equipment-free and specific detection of HBV and HDV. This review will provide some insight into both existing and diagnosis tools under development, their applicability in developing countries and how they could increase screening, patient monitoring and treatment eligibility.
Collapse
Affiliation(s)
- Amie Ceesay
- INSERM U1052, CNRS UMR-5286, Cancer Research Center of Lyon (CRCL), 69008 Lyon, France
- Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine, Atlantic Boulevard, Fajara P.O. Box 273, Banjul, The Gambia
- School of Arts and Sciences, University of The Gambia, Serrekunda P.O. Box 3530, Banjul, The Gambia
| | - Khaled Bouherrou
- INSERM U1052, CNRS UMR-5286, Cancer Research Center of Lyon (CRCL), 69008 Lyon, France
| | - Boun Kim Tan
- INSERM U1052, CNRS UMR-5286, Cancer Research Center of Lyon (CRCL), 69008 Lyon, France
- Department of Intensive Care Unit, Hôpital Lyon Sud, Hospices Civils de Lyon, 165, Chemin du Grand Revoyet, 69310 Pierre-Bénite, France
| | - Maud Lemoine
- Division of Digestive Diseases, Section of Hepatology, Department of Metabolism, Digestion and Reproduction, Imperial College London, London W2 1NY, UK
| | - Gibril Ndow
- Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine, Atlantic Boulevard, Fajara P.O. Box 273, Banjul, The Gambia
| | - Barbara Testoni
- INSERM U1052, CNRS UMR-5286, Cancer Research Center of Lyon (CRCL), 69008 Lyon, France
| | - Isabelle Chemin
- INSERM U1052, CNRS UMR-5286, Cancer Research Center of Lyon (CRCL), 69008 Lyon, France
| |
Collapse
|
|
16
|
A Predictive Model to Evaluate the HbeAg Positivity of Chronic Hepatitis B Virus Patients in Clinics: A Cross-Sectional Study. Medicina (B Aires) 2022; 58:medicina58091279. [PMID: 36143956 PMCID: PMC9500857 DOI: 10.3390/medicina58091279] [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: 06/23/2022] [Revised: 08/31/2022] [Accepted: 09/11/2022] [Indexed: 11/17/2022] Open
Abstract
Background and Objective: The study aims to investigate the correlation between Hepatitis B ‘e’ antigen (HBeAg) and HBV DNA levels, and to find a convenient tool to estimate the HBV DNA level for clinicians. Materials and Methods: We enrolled 1020 patients in this cross-sectional study and divided them into four groups: an HbeAg-positive and -negative group, and high and low HBV DNA levels groups. Results: Alanine aminotransferase (ALT), Albumin (ALB) and HBeAg are independent risk factors for CHB patients. When the level of HBeAg is higher than 16.15 S/CO, it is four times more likely that the patients will have high levels of HBV DNA than those who do not. The ALT and TB are independent risk factors in HBeAg-negative patients with a high HBV DNA level. We have drawn three predictive models to estimate the HBV DNA levels for those with the chronic hepatitis B virus (CHB), and those that are HBeAg-positive and HBeAg-negative (Y1 = 0.004 × ALT(IU/L) + 1.412 × HBeAg (S/CO) − 0.029 × ALB (g/L) + 0.779, the AUC is 0.672, and the cutoff value is −0.072, there the sensitivity is 0.615, the specificity is 0.648, PPV is 65.182% and NPV is 60.837%; Y2 = 0.007 × HBeAg (S/CO) − 0.016 × HGB (g/L) + 3.070, the AUC is 0.724, and the cutoff value is 1.216, where the sensitivity is 0.626, the specificity is 0.897, PPV is 94.118% and NPV is 34.437%; Y3 = −0.005 × ALT(IU/L) + 0.006 × TB (umol/L) + 0.385, the AUC is 0.661, and the cutoff value is 0.263, where the sensitivity is 0.677, the specificity is 0.587, PPV is 66.820% and NPV is 40.774%, respectively). We propose that HBeAg is the most important risk factor for the patient with a high HBV DNA level, however, it is not as important in the HBeAg-positive group. Conclusions: HBeAg is an independent risk factor that reflects the level of HBV DNA with a strong correlation. Patient with HBeAg (−) should combine TB and ALT to estimate the level of HBV DNA.
Collapse
|
|
17
|
Chu JH, Huang Y, Xie DY, Deng H, Wei J, Guan YJ, Li GJ, Zeng YL, Yang JH, Chen XY, Shang J, Li JB, Gao N, Gao ZL. Real-world study on HBsAg loss of combination therapy in HBeAg-negative chronic hepatitis B patients. J Viral Hepat 2022; 29:765-776. [PMID: 35718996 DOI: 10.1111/jvh.13722] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 04/11/2022] [Accepted: 05/21/2022] [Indexed: 12/22/2022]
Abstract
Combination therapy with pegylated interferon (PEG-IFN) and nucleos(t)ide analogues (NAs) can enhance hepatitis B surface antigen (HBsAg) clearance. However, the specific treatment strategy and the patients who would benefit the most are unclear. Therefore, we assessed the HBsAg loss rate of add-on PEG-IFN and explored the factors associated with HBsAg loss in chronic hepatitis B (CHB) patients. This was a real-world cohort study of adults with CHB. Hepatitis B e antigen (HBeAg)-negative NAs-treated patients with baseline HBsAg ≤1500 IU/ml and HBV DNA < the lower limit of detection, or 100 IU/ml, received 48 weeks of add-on PEG-IFN. The primary outcome of the study was the rate of HBsAg loss at 48 weeks of combination treatment. Using multivariable logistic regression analysis, we determined factors associated with HBsAg loss. HBsAg loss in 2579 patients (mean age: 41.2 years; 80.9% male) was 36.7% (947 patients) at 48 weeks. HBsAg loss was highest in patients from south-central and southwestern China (40.0%). Factors independently associated with HBsAg loss included: increasing age (odds ratio = 0.961); being male (0.543); baseline HBsAg level (0.216); HBsAg decrease at 12 weeks (between 0.5 and 1.0 log10 IU/ml [2.405] and >1.0 log10 IU/ml [7.370]); alanine aminotransferase (ALT) increase at 12 weeks (1.365); haemoglobin (HGB) decrease at 12 weeks (1.558). There was no difference in the primary outcomes associated with the combination regimen. In conclusion, HBsAg loss by combination therapy was higher in patients from southern China than those from the north. An increased chance of HBsAg loss was associated with baseline characteristics and dynamic changes in clinical indicators.
Collapse
Affiliation(s)
- Jun-Hao Chu
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Yan Huang
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Dong-Ying Xie
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.,Guandong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.,Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, Guangzhou, Guangdong, China
| | - Hong Deng
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.,Guandong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.,Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, Guangzhou, Guangdong, China
| | - Jia Wei
- Department of Gastroenterology, the Second People's Hospital Yunnan Province, Kunming, Yunnan, China
| | - Yu-Juan Guan
- Department of Hepatology, Guangzhou Eighth People's Hospital, Guangzhou, Guangdong, China
| | - Guo-Jun Li
- Department of Hepatology, Shenzhen Third People's Hospital, Shenzhen, Guangdong, China
| | - Yi-Lan Zeng
- Department of Hepatology, Chengdu Public Health Clinical Medical Center, Chengdu, Sichuan, China
| | - Jia-Hong Yang
- Department of Infectious Diseases, Deyang People's Hospital, Deyang, Sichuan, China
| | - Xin-Yue Chen
- Department of Hepatology, Beijing You'an Hospital, Capital Medical University, Beijing, China
| | - Jia Shang
- Department of Infectious Diseases, Henan Provincial People's Hospital, Zhengzhou, Henan, China
| | - Jia-Bin Li
- Department of Infectious Diseases, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Na Gao
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Zhi-Liang Gao
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.,Guandong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.,Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, Guangzhou, Guangdong, China
| |
Collapse
|
|
18
|
Detectability of Hepatitis B Virus in Peripheral Blood Mononuclear Cells Among Naive Chronic Hepatitis B Patients With Negative Viremia. INFECTIOUS DISEASES IN CLINICAL PRACTICE 2022. [DOI: 10.1097/ipc.0000000000001153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
|
|
19
|
Chung GE, Kim JY, Shin H, Hong JH, Hur MH, Cho H, Park MK, Choi NR, Kim J, Lee YB, Cho EJ, Yu SJ, Kim YJ, Yoon JH, Lee JH. Correlation between Results of Semi-Quantitative and Quantitative Tests for Hepatitis B Virus Surface Antigen among Patients Achieving Viral Suppression with Antiviral Treatment. Diagnostics (Basel) 2022; 12:diagnostics12071757. [PMID: 35885659 PMCID: PMC9317496 DOI: 10.3390/diagnostics12071757] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 07/13/2022] [Accepted: 07/19/2022] [Indexed: 11/16/2022] Open
Abstract
Background: Hepatitis B virus (HBV) infection remains a threat to global public health. Serum hepatitis B surface antigen (HBsAg) has been used in screening for HBV infection. Quantitative HBsAg assays are useful for monitoring the natural history of HBV infection and its response to therapy. The aim of this study was to determine the relationship between quantitative (qHBsAg; IU/mL) and semi-quantitative (sqHBsAg; signal-to-cutoff ratio [S/Co]) HBsAg titers in patients with chronic hepatitis B (CHB). Methods: We retrospectively included 284 samples with HBV DNA < 20 IU/mL from patients who had simultaneous qHBsAg (using electrochemiluminescence assay) and sqHBsAg tests. Patients were grouped according to their serum HBV-envelope antigen (HBeAg) status (HBeAg-negative, n = 239 and HBeAg-positive, n = 45). The Spearman test was used to analyze the correlation between the quantitative and semi-quantitative assays. Results: There was a significant linear correlation between sqHBsAg and qHBsAg in the HBeAg-negative patients (qHBsAg [IU/mL] = 0.0094 × sqHBsAg [S/Co]1.323; adjusted R2 = 0.8445; p < 0.001). There was a substantial hook effect in the assays from the HBeAg-positive patients, so we performed a stratified analysis according to qHBsAg <1000 IU/mL or ≥1000 IU/mL and found a significant positive linear correlation between sqHBsAg S/Co and qHBsAg (qHBsAg [IU/mL] = 0.072 × sqHBsAg [S/Co]1.331; adjusted R2 = 0.7878; p < 0.001) in HBeAg-positive patients with qHBsAg titers of <1000 IU/mL and a significant negative correlation in HBeAg-positive patients with qHBsAg titers of ≥1000 IU/mL (qHBsAg [IU/mL] = 8.987 × 1014 × sqHBsAg [S/Co]−3.175; adjusted R2 = 0.6350; p < 0.001). Conclusions: There was a highly linear, positive correlation between qHBsAg and sqHBsAg in HBeAg-negative CHB patients. The hook effect led to a negative correlation in HBeAg-positive CHB patients with qHBsAg titers ≥1000 IU/mL.
Collapse
Affiliation(s)
- Goh Eun Chung
- Department of Internal Medicine, Healthcare Research Institute, Gangnam Healthcare Center, Seoul National University Hospital, Seoul 03080, Korea;
| | - Ju Yeon Kim
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea; (J.Y.K.); (H.S.); (J.H.H.); (M.H.H.); (H.C.); (M.K.P.); (N.R.C.); (J.K.); (Y.B.L.); (E.J.C.); (S.J.Y.); (Y.J.K.); (J.-H.Y.)
| | - Hyunjae Shin
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea; (J.Y.K.); (H.S.); (J.H.H.); (M.H.H.); (H.C.); (M.K.P.); (N.R.C.); (J.K.); (Y.B.L.); (E.J.C.); (S.J.Y.); (Y.J.K.); (J.-H.Y.)
| | - Ji Hoon Hong
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea; (J.Y.K.); (H.S.); (J.H.H.); (M.H.H.); (H.C.); (M.K.P.); (N.R.C.); (J.K.); (Y.B.L.); (E.J.C.); (S.J.Y.); (Y.J.K.); (J.-H.Y.)
| | - Moon Haeng Hur
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea; (J.Y.K.); (H.S.); (J.H.H.); (M.H.H.); (H.C.); (M.K.P.); (N.R.C.); (J.K.); (Y.B.L.); (E.J.C.); (S.J.Y.); (Y.J.K.); (J.-H.Y.)
| | - Heejin Cho
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea; (J.Y.K.); (H.S.); (J.H.H.); (M.H.H.); (H.C.); (M.K.P.); (N.R.C.); (J.K.); (Y.B.L.); (E.J.C.); (S.J.Y.); (Y.J.K.); (J.-H.Y.)
| | - Min Kyung Park
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea; (J.Y.K.); (H.S.); (J.H.H.); (M.H.H.); (H.C.); (M.K.P.); (N.R.C.); (J.K.); (Y.B.L.); (E.J.C.); (S.J.Y.); (Y.J.K.); (J.-H.Y.)
| | - Na Ryung Choi
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea; (J.Y.K.); (H.S.); (J.H.H.); (M.H.H.); (H.C.); (M.K.P.); (N.R.C.); (J.K.); (Y.B.L.); (E.J.C.); (S.J.Y.); (Y.J.K.); (J.-H.Y.)
| | - Jihye Kim
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea; (J.Y.K.); (H.S.); (J.H.H.); (M.H.H.); (H.C.); (M.K.P.); (N.R.C.); (J.K.); (Y.B.L.); (E.J.C.); (S.J.Y.); (Y.J.K.); (J.-H.Y.)
| | - Yun Bin Lee
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea; (J.Y.K.); (H.S.); (J.H.H.); (M.H.H.); (H.C.); (M.K.P.); (N.R.C.); (J.K.); (Y.B.L.); (E.J.C.); (S.J.Y.); (Y.J.K.); (J.-H.Y.)
| | - Eun Ju Cho
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea; (J.Y.K.); (H.S.); (J.H.H.); (M.H.H.); (H.C.); (M.K.P.); (N.R.C.); (J.K.); (Y.B.L.); (E.J.C.); (S.J.Y.); (Y.J.K.); (J.-H.Y.)
| | - Su Jong Yu
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea; (J.Y.K.); (H.S.); (J.H.H.); (M.H.H.); (H.C.); (M.K.P.); (N.R.C.); (J.K.); (Y.B.L.); (E.J.C.); (S.J.Y.); (Y.J.K.); (J.-H.Y.)
| | - Yoon Jun Kim
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea; (J.Y.K.); (H.S.); (J.H.H.); (M.H.H.); (H.C.); (M.K.P.); (N.R.C.); (J.K.); (Y.B.L.); (E.J.C.); (S.J.Y.); (Y.J.K.); (J.-H.Y.)
| | - Jung-Hwan Yoon
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea; (J.Y.K.); (H.S.); (J.H.H.); (M.H.H.); (H.C.); (M.K.P.); (N.R.C.); (J.K.); (Y.B.L.); (E.J.C.); (S.J.Y.); (Y.J.K.); (J.-H.Y.)
| | - Jeong-Hoon Lee
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea; (J.Y.K.); (H.S.); (J.H.H.); (M.H.H.); (H.C.); (M.K.P.); (N.R.C.); (J.K.); (Y.B.L.); (E.J.C.); (S.J.Y.); (Y.J.K.); (J.-H.Y.)
- Correspondence: ; Tel.: +82-2-2072-2228
| |
Collapse
|
|
20
|
Broquetas T, Carrión JA. Current Perspectives on Nucleos(t)ide Analogue Therapy for the Long-Term Treatment of Hepatitis B Virus. Hepat Med 2022; 14:87-100. [PMID: 35936810 PMCID: PMC9346298 DOI: 10.2147/hmer.s291976] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 07/12/2022] [Indexed: 01/27/2023] Open
Affiliation(s)
- Teresa Broquetas
- Liver Section, Gastroenterology Department, Hospital del Mar, Barcelona, Spain
- IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain
| | - José A Carrión
- Liver Section, Gastroenterology Department, Hospital del Mar, Barcelona, Spain
- IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain
- Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona, Spain
| |
Collapse
|
|
21
|
Hawkins C, Kang M, Bhattacharya D, Cloherty G, Kuhns M, Matining R, Thio C, Samaneka W, Chinula L, Mulinda N, Badal-Faesen S, Sugandhavesa P, Lama J, Gaseitsiwe S, Holzmayer V, Anderson M, Murphy R, Peters M. Hepatitis B surface antigen and hepatitis B RNA changes in HIV/hepatitis B virus co-infected participants receiving hepatitis B virus-active antiretroviral therapy. AIDS 2022; 36:975-984. [PMID: 35165216 PMCID: PMC9167724 DOI: 10.1097/qad.0000000000003193] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
INTRODUCTION With advances in hepatitis B virus (HBV) therapies, there is a need to identify serum biomarkers that assess the HBV covalently closed circular DNA (cccDNA) reservoir and predict functional cure in HIV/HBV co-infection. METHODS In this retrospective study, combining samples from HIV/HBV co-infected participants enrolled in two ACTG interventional trials, proportions achieving HBsAg less than 0.05 log10 IU/ml and HBV RNA less than log10 1.65 U/ml or not detected (LLoQ/NEG) in response to DUAL [tenofovir TDF+emtricitabine (FTC)] vs. MONO [FTC or lamivudine (3TC)] HBV-active ART, were measured. Predictors of qHBsAg less than 0.05 log10 IU/ml were evaluated in logistic regression models. RESULTS There were 88 participants [58% women, median age 34; 47 on DUAL vs. 41 on MONO HBV-active ART]. Twenty-one percent achieved HBsAg less than 0.05 log10 IU/ml (30% DUAL vs. 10% MONO). Time to HBsAg less than 0.05 log10 IU/ml was lower (P = 0.02) and the odds of achieving HBsAg less than 0.05 log10 IU/ml were higher (P = 0.07) in DUAL participants. HBV RNA became less than LLoQ/NEG in 47% (DUAL 60% vs. MONO 33%). qHBsAg less than 3 log10 IU/ml was the strongest predictor of HBsAg less than 0.05 log10 IU/ml. CONCLUSION This study supports current recommendations of TDF-based DUAL-HBV active ART for initial use in HIV/HBV co-infection. HBV RNA could be a useful marker of treatment response in HIV/HBV co-infected patients on HBV-active ART.
Collapse
Affiliation(s)
- Claudia Hawkins
- Department of Medicine, Feinberg School of Medicine, Northwestern University CRS, Chicago, Illinois
| | - Minhee Kang
- Center for Biostatistics in AIDS Research, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Debika Bhattacharya
- David Geffen School of Medicine, Division of Infectious Diseases, University of California, Los Angeles (UCLA), California
| | - Gavin Cloherty
- Infectious Diseases Research, Abbott, Abbott Park, Illinois
| | - Mary Kuhns
- Infectious Diseases Research, Abbott, Abbott Park, Illinois
| | - Roy Matining
- Center for Biostatistics in AIDS Research, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Chloe Thio
- Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
| | | | - Lameck Chinula
- UNC Project Malawi CRS, UNC Department of Obstetrics and Gynecology's Division of Global Women's Health, Chapel Hill, North Carolina, USA
| | | | - Sharlaa Badal-Faesen
- Clinical HIV Research Unit, Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | | | - Javier Lama
- Asociacion Civil Impacta Salud y Educacion, Lima, Peru, and Botswana Harvard School of Public Health AIDS Initiative Partnership, Botswana
| | - Simani Gaseitsiwe
- Clinical HIV Research Unit, Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Vera Holzmayer
- Infectious Diseases Research, Abbott, Abbott Park, Illinois
| | - Mark Anderson
- Infectious Diseases Research, Abbott, Abbott Park, Illinois
| | - Robert Murphy
- Department of Medicine, Feinberg School of Medicine, Northwestern University CRS, Chicago, Illinois
| | - Marion Peters
- Department of Medicine, Feinberg School of Medicine, Northwestern University CRS, Chicago, Illinois
| |
Collapse
|
|
22
|
Bushen Jianpi Formula Combined with Entecavir for the Treatment of HBeAg-Negative Chronic Hepatitis B: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:6097221. [PMID: 35368769 PMCID: PMC8975667 DOI: 10.1155/2022/6097221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 02/28/2022] [Accepted: 03/03/2022] [Indexed: 11/17/2022]
Abstract
Background Bushen Jianpi formula (BSJPF, also known as Lingmao formula) is a traditional Chinese medicine for chronic hepatitis B (CHB). The previous study has suggested that the treatment combination of BSJPF and entecavir (ETV) can achieve a significant loss of hepatitis B e antigen (HBeAg) and a significant decrease in serum level of hepatitis B virus (HBV) DNA in HBeAg-positive CHB patients with mildly elevated alanine aminotransferase. Objective This study aimed to evaluate the efficacy and safety of BSJPF combined with ETV for treating HBeAg-negative CHB patients. Methods A total of 640 patients were assigned randomly to the treatment group (receiving BSJPF combined with ETV for 96 weeks) or the control group (receiving a placebo combined with ETV for 96 weeks) in a 1 : 1 ratio. The primary endpoints are the rate of loss of hepatitis B surface antigen (HBsAg). The secondary outcomes included the rate of decrease in the HBsAg concentration to ≥1 lg·IU/mL, the HBV DNA suppression, the decline of the level of covalently closed circular DNA (cccDNA) in the liver, histological improvements, and the rate of ALT normalization. Results The rate of HBsAg loss in the treatment group was significantly higher than that of the control group (5.5% versus 1.8%, P=0.031). There were 11.1% of patients in the treatment group who recorded a reduction in HBsAg ≥1 lg·IU/mL, which is better than 5.9% of patients in the control group (P=0.043). There was no significant difference between the two groups with regard to the rate of HBV DNA clearance, the reduction in intrahepatic cccDNA, and the rate of ALT normalization (P > 0.05). The rate of liver fibrosis improvement in the treatment group was better than that of the control group (35.5% versus 11.8%, P=0.031), but there was no difference in necroinflammatory improvement (P > 0.05). The adverse events (AEs) were similar between the two groups, except for the abnormal kidney function, with 2.2% in the control group and 0.0% in the treatment group (P=0.028). Conclusion The combination of BSJPF and ETV can increase the rate of HBsAg loss and the rate of histological fibrosis improvement without serious adverse events in CHB patients. Trial Registration. This trial is registered with ChiCTR-IOR-16009880 on November 16, 2016—retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=16836.
Collapse
|
|
23
|
Hayashi S, Isogawa M, Kawashima K, Ito K, Chuaypen N, Morine Y, Shimada M, Higashi-Kuwata N, Watanabe T, Tangkijvanich P, Mitsuya H, Tanaka Y. Droplet digital PCR assay provides intrahepatic HBV cccDNA quantification tool for clinical application. Sci Rep 2022; 12:2133. [PMID: 35136096 PMCID: PMC8826402 DOI: 10.1038/s41598-022-05882-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 01/13/2022] [Indexed: 12/14/2022] Open
Abstract
The persistence of covalently closed circular DNA (cccDNA) poses a major obstacle to curing chronic hepatitis B (CHB). Here, we used droplet digital PCR (ddPCR) for cccDNA quantitation. The cccDNA-specific ddPCR showed high accuracy with the dynamic range of cccDNA detection from 101 to 105 copies/assay. The ddPCR had higher sensitivity, specificity and precisely than qPCR. The results of ddPCR correlated closely with serum HB core-related antigen and HB surface antigen (HBsAg) in 24 HBV-infected human-liver-chimeric mice (PXB-mice). We demonstrated that in 2 PXB-mice after entecavir treatment, the total cccDNA content did not change during liver repopulation, although the cccDNA content per hepatocyte was reduced after the treatment. In the 6 patients with HBV-related hepatocellular carcinoma, ddPCR detected cccDNA in both tumor and non-tumor tissues. In 13 HBeAg-negative CHB patients with pegylated interferon alpha-2a, cccDNA contents from paired biopsies were more significantly reduced in virological response (VR) than in non-VR at week 48 (p = 0.0051). Interestingly, cccDNA levels were the lowest in VR with HBsAg clearance but remained detectable after the treatment. Collectively, ddPCR revealed that cccDNA content is stable during hepatocyte proliferation and persists at quantifiable levels, even after serum HBsAg clearance.
Collapse
Affiliation(s)
- Sanae Hayashi
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Masanori Isogawa
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Keigo Kawashima
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Kyoko Ito
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Natthaya Chuaypen
- Center of Excellence in Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Yuji Morine
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Mitsuo Shimada
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Nobuyo Higashi-Kuwata
- Department of Refractory Viral Infections, National Center for Global Health and Medicine Research Institute, Tokyo, Japan
| | - Takehisa Watanabe
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Pisit Tangkijvanich
- Center of Excellence in Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Hiroaki Mitsuya
- Department of Refractory Viral Infections, National Center for Global Health and Medicine Research Institute, Tokyo, Japan
- Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
- Department of Clinical Sciences, Kumamoto University Hospital, Kumamoto, Japan
| | - Yasuhito Tanaka
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
| |
Collapse
|
|
24
|
Alpsoy A, Adanir H, Bayramoglu Z, Elpek GO. Correlation of hepatitis B surface antigen expression with clinicopathological and biochemical parameters in liver biopsies: A comprehensive study. World J Hepatol 2022; 14:260-273. [PMID: 35126853 PMCID: PMC8790405 DOI: 10.4254/wjh.v14.i1.260] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 07/10/2021] [Accepted: 12/31/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Chronic viral B hepatitis (CHB) is a potentially life-threatening liver disease that may progress to liver failure and cirrhosis. Currently, although combinations of different laboratory methods are used in the follow-up and treatment of CHB, the failure of these procedures in some cases has led to the necessity of developing new approaches. In CHB, the intrahepatic expression pattern of viral antigens, including hepatitis B surface antigen (HBsAg), is related to different phases of inflammation. However, many studies have focused on the intracytoplasmic properties of HBsAg staining, and HBsAg positivity in liver tissue has not been evaluated by objective quantitative methods. AIM To investigate the relationship of image analysis-based quantitative HBsAg expression and its staining patterns with clinicopathological factors and treatment in CHB. METHODS A total of 140 liver biopsies from treatment-naïve cases with CHB infection were included in this study. Following diagnosis, all patients were treated with entecavir (0.5 mg) and followed up at three-month intervals. The percentage of immunohistochemical HBsAg (p-HBsAg) expression in the liver was determined in whole tissue sections of biopsies from each case by image analysis. The immunohistochemical staining pattern was also evaluated separately according to 3 different previously defined classifications. RESULTS A positive correlation between p-HBsAg and serum levels of hepatitis B virus (HBV) DNA and HBsAg was observed (P < 0.001). The p-HBsAg value was significantly higher in younger patients than in older patients. When the groups were categorized according to the hepatitis B e antigen (HBeAg) status in HBeAg-positive cases, p-HBsAg was correlated with HBV DNA, hepatitis activity index (HAI) and fibrosis scores (P < 0.001). In this group, p-HBsAg and HBsAg expression patterns were also correlated with the viral response (VR) and the serological response (SR) (P < 0.001). Multivariate analysis revealed that p-HBsAg was an independent predictor of either VR or SR (P < 0.001). In HBeAg-negative patients, although HBsAg expression patterns were correlated with both HAI and fibrosis, no relationship was observed among p-HBsAg, clinicopathological factors and VR. CONCLUSION In pretreatment liver biopsies, the immunohistochemical determination of HBsAg expression by quantitative methods, beyond its distribution within the cell, may be a good predictor of the treatment response, especially in HBeAg-positive cases.
Collapse
Affiliation(s)
- Anil Alpsoy
- Department of Pathology, Akdeniz University, Medical School, Antalya 07070, Turkey
| | - Haydar Adanir
- Department of Gastroenterology, Akdeniz University, Medical School, Antalya 07070, Turkey
| | - Zeynep Bayramoglu
- Department of Pathology, Akdeniz University, Medical School, Antalya 07070, Turkey
| | - Gulsum Ozlem Elpek
- Department of Pathology, Akdeniz University, Medical School, Antalya 07070, Turkey.
| |
Collapse
|
|
25
|
Charatcharoenwitthaya P, Kaewdech A, Piratvisuth T. Controversies in Treating Chronic HBV: The Role of PEG-interferon-alfa. Clin Liver Dis 2021; 25:741-762. [PMID: 34593151 DOI: 10.1016/j.cld.2021.06.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Pegylated interferon-alpha therapy is one of the first-line chronic hepatitis B treatment. Finite treatment duration, absence of drug resistance, delayed response, and higher hepatitis B surface antigen loss than nucleos(t)ides analog therapy are the advantages of pegylated interferon-alpha treatment. Common side effects and subcutaneous injections requirement limit its use. Identifying patients likely to respond to pegylated interferon-alpha and optimizing treatment is reasonable. Motivating patients to complete the 48-week treatment is necessary. Treatment is stopped or switched to other treatment strategies in patients with stopping rule criteria. Combination therapy with nucleos(t)ides analog may improve response, but remains controversial.
Collapse
Affiliation(s)
- Phunchai Charatcharoenwitthaya
- Gastroenterology Division, Department of Internal Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Wang-Lang Road, Bangkok 10700, Thailand
| | - Apichat Kaewdech
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Kanchanawanich Road, Songkhla 90110, Thailand
| | - Teerha Piratvisuth
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Kanchanawanich Road, Songkhla 90110, Thailand; NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Prince of Songkla University, Kanchanawanich Road, Songkhla 90110, Thailand.
| |
Collapse
|
|
26
|
Abstract
Hepatitis B was discovered by researchers who were investigating jaundice associated with blood transfusions as well as parenterally administered medications. Through trial and error, the HBV was identified. There are specific tests that detect HBV infection, whether it is a previous exposure or active infection. The various HBV serologies are reviewed in this work as well. Hepatitis B surface antigen has emerged as a tool in defining treatment endpoint and its significance is reviewed. HBV genotypes are distributed uniquely throughout the world, in particular, genotype C is associated with higher rates of hepatocellular carcinoma. Various HBV genotypes and their impact on the clinical course are discussed. The relationship of HBV serologies and HBV DNA to disease progression is outlined. There are specific recommendations on monitoring those infected with HBV and this is reviewed here. HBV mutations have an impact on the disease course and those of significance are also discussed.
Collapse
|
|
27
|
Zhang H, Tu T. Approaches to quantifying Hepatitis B Virus covalently closed circular (ccc)DNA. Clin Mol Hepatol 2021; 28:135-149. [PMID: 34674513 PMCID: PMC9013611 DOI: 10.3350/cmh.2021.0283] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 10/21/2021] [Indexed: 11/19/2022] Open
Abstract
Chronic hepatitis B is a major cause of liver disease worldwide and is currently incurable. Hepatitis B virus (HBV) covalently closed circular (ccc) DNA is a key form of the virus responsible for its persistence and is the transcriptional template for all viral transcripts. The field is focussed on methods to clear HBV cccDNA but this been limited by technical difficulties in its quantification due to: identical sequence to other forms of HBV DNA; low copy number per cell; and high resistance to denaturation by heat, leading to difficulty using polymerase chain reaction or hybridization methods for detection. A number of assays have been developed in order to overcome these hurdles either directly or detecting cccDNA levels indirectly via its transcriptional products. In this review, we summarize the approaches to cccDNA quantification that are currently used, and outline key open questions in the cccDNA biology field which remain to be answered due to the limitations of current methods.
Collapse
Affiliation(s)
- Henrik Zhang
- Storr Liver Centre, Westmead Clinical School and Westmead Institute for Medical Research, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW 2145, Australia
| | - Thomas Tu
- Storr Liver Centre, Westmead Clinical School and Westmead Institute for Medical Research, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW 2145, Australia.,Centre for Infectious Diseases and Microbiology, Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney at Westmead Hospital, Westmead NSW 2145, Australia
| |
Collapse
|
|
28
|
Nasser M, Zayed N, Gamal Eldeen H, Abdo M, Kabara Y, Elserafy M. Inter-method variability of hepatitis B surface antigen quantification in a cohort of Egyptian patients with chronic hepatitis B virus. Arab J Gastroenterol 2021; 22:151-157. [PMID: 34090829 DOI: 10.1016/j.ajg.2021.05.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Revised: 01/30/2021] [Accepted: 05/04/2021] [Indexed: 12/01/2022]
Abstract
BACKGROUND AND STUDY AIMS Hepatitis B (HB) surface antigen (HBsAg) levels can predict clinical and treatment outcomes in chronic HB virus (HBV) infection. We aimed to compare the performance of two different assays [Elecsys® (Roche) and Architect™ (Abbott)] for HBsAg quantification and evaluate HBsAg levels in the various immune phases in a cohort of Egyptian patients with chronic HBV. PATIENTS AND METHODS Quantitative HBsAg by Elecsys® and Architect™ assays, measurement of routine biochemical and serological markers, and transient elastography were performed in 92 patients with chronic HBV. Results of the two assays and other tests were compared. RESULTS Ninety-two treatment-naive patients with chronic HBV, (70% males; mean age, 36.1 ± 10.5 years) were recruited from Cairo Fatemic Hospital. Patients were categorized as HBeAg positive (n = 22) and HBeAg negative (n = 70). The Architect™ and Elecsys® assays were significantly correlated (intraclass correlation coefficient: 0.913; 95% CI: 0.870-0.943; p < 0.001). However, Deming regression, Passing and Bablok, and Bland-Altman statistical analyses showed discordance among the assays. HBsAg levels by both assays were significantly higher in the HBeAg positive than patients with HBeAg-negative (p = 0.033 and 0.013, respectively). HBsAg levels in the Architect™ and Elecsys® assays were significantly higher in HBeAg-negative chronic hepatitis than in HBeAg-negative chronic infection (p = 0.002 and 0.004, respectively) CONCLUSION: Both assays for qHBsAg were found to be simple and reproducible tests that could classify patients and provide additional evidence on the natural history of HBV.
Collapse
Affiliation(s)
- Mona Nasser
- Clinical Pathology, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt
| | - Naglaa Zayed
- Endemic Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt
| | | | - Mahmoud Abdo
- Endemic Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Younan Kabara
- Endemic Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Magdy Elserafy
- Endemic Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt
| |
Collapse
|
|
29
|
Vachon A, Osiowy C. Novel Biomarkers of Hepatitis B Virus and Their Use in Chronic Hepatitis B Patient Management. Viruses 2021; 13:951. [PMID: 34064049 PMCID: PMC8224022 DOI: 10.3390/v13060951] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 05/17/2021] [Accepted: 05/18/2021] [Indexed: 12/15/2022] Open
Abstract
Even though an approved vaccine for hepatitis B virus (HBV) is available and widely used, over 257 million individuals worldwide are living with chronic hepatitis B (CHB) who require monitoring of treatment response, viral activity, and disease progression to reduce their risk of HBV-related liver disease. There is currently a lack of predictive markers to guide clinical management and to allow treatment cessation with reduced risk of viral reactivation. Novel HBV biomarkers are in development in an effort to improve the management of people living with CHB, to predict disease outcomes of CHB, and further understand the natural history of HBV. This review focuses on novel HBV biomarkers and their use in the clinical setting, including the description of and methodology for quantification of serum HBV RNA, hepatitis B core-related antigen (HBcrAg), quantitative hepatitis B surface antigen (qHBsAg), including ultrasensitive HBsAg detection, quantitative anti-hepatitis B core antigen (qAHBc), and detection of HBV nucleic acid-related antigen (HBV-NRAg). The utility of these biomarkers in treatment-naïve and treated CHB patients in several clinical situations is further discussed. Novel HBV biomarkers have been observed to provide critical clinical information and show promise for improving patient management and our understanding of the natural history of HBV.
Collapse
Affiliation(s)
- Alicia Vachon
- Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB R3E 0J9, Canada;
- National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada
| | - Carla Osiowy
- Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB R3E 0J9, Canada;
- National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada
| |
Collapse
|
|
30
|
Li M, Zhang L, Lu Y, Chen Q, Lu H, Sun F, Zeng Z, Wan G, Zhao L, Xie Y. Early Serum HBsAg Kinetics as Predictor of HBsAg Loss in Patients with HBeAg-Negative Chronic Hepatitis B after Treatment with Pegylated Interferonα-2a. Virol Sin 2021; 36:311-320. [PMID: 32975731 PMCID: PMC8087759 DOI: 10.1007/s12250-020-00290-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2020] [Accepted: 07/16/2020] [Indexed: 01/05/2023] Open
Abstract
Hepatitis B surface antigen (HBsAg) loss is an ideal treatment endpoint for patients with chronic hepatitis B (CHB). We investigated the predictive value of on-treatment HBsAg levels for HBsAg loss in hepatitis B e antigen (HBeAg)-negative CHB patients who received 120-week PEG-IFNα-2a treatment. Serum HBV DNA, HBsAg, and anti-HBs levels were assayed at baseline and every 3 months during the treatment. Of 81 patients, 12 achieved HBsAg loss, 20 achieved HBsAg < 100 IU/mL, and 49 maintained HBsAg ≥ 100 IU/mL. HBsAg loss rate was only 3.7% at 48 weeks, while it reached to 11.1% and 14.8% after treatment of 96 weeks and 120 weeks. The cutoff HBsAg levels at 12 weeks predicting HBsAg loss at 96 weeks and 120 weeks of treatment were 400 IU/mL and 750 IU/mL, with AUC 0.725 and 0.722, positive predictive value (PPV) 29.41% and 30.56%, and negative predictive value (NPV) 93.75% and 97.78%, respectively. The cutoff HBsAg levels at 24 weeks predicting HBsAg loss at 96 weeks and 120 weeks of treatment were 174 IU/mL and 236 IU/mL respectively, with AUC 0.925 and 0.922, PPV 40.0% and 46.15%, and both NPV 100%. The predictive ability of the cutoff HBsAg levels at 24 weeks was better than that at 12 weeks for HBsAg loss at either 96 or 120 weeks (χ2 = 3.880, P = 0.049 and χ2 = 4.412, P = 0.036). These results indicate that extended therapy is critical to HBsAg loss in HBeAg-negative CHB patients during PEG-IFN treatment, and the HBsAg level at 24 weeks can be used to predict HBsAg loss during tailoring PEG-IFN therapy.
Collapse
Affiliation(s)
- Minghui Li
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, 100015, China
| | - Lu Zhang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China
| | - Yao Lu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China
| | - Qiqi Chen
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, 100015, China
| | - Huihui Lu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China
| | - Fangfang Sun
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China
| | - Zhan Zeng
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, 100015, China
| | - Gang Wan
- Department of Biostatistics, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China
| | - Linqing Zhao
- Laboratory of Virology Capital Institute of Pediatrics, Beijing, 100020, China.
| | - Yao Xie
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, 100015, China.
| |
Collapse
|
|
31
|
Hsu CW, Chu YD, Lai MW, Lin CL, Liang KH, Lin YH, Yeh CT. Hepatitis B Virus Covalently Closed Circular DNA Predicts Postoperative Liver Cancer Metastasis Independent of Virological Suppression. Cancers (Basel) 2021; 13:cancers13030538. [PMID: 33572617 PMCID: PMC7867012 DOI: 10.3390/cancers13030538] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Revised: 01/19/2021] [Accepted: 01/27/2021] [Indexed: 02/07/2023] Open
Abstract
New antiviral therapies against hepatitis B virus (HBV) focus on the elimination of covalently closed circular DNA (cccDNA). However, traditional cccDNA-specific quantitative PCR (qPCR) has a narrow effective range, hindering a reliable comparison between the levels of biopsy-derived cccDNAs. Collaterally, the prognostic role of cccDNA in HBV-related hepatocellular carcinoma (HCC) cannot be clearly defined. Here, we developed a peptide nucleic acid (PNA)-clamping qPCR method to provide a wider range of specific cccDNA quantification (up to 5 logs of effective range). Extrachromosomal DNA was extracted from para-neoplastic tissues for cccDNA quantification. In total, 350 HBV-related HCC patients were included for an outcome analysis. Without differential pre-dilution, cccDNA levels in para-neoplastic liver tissues were determined, ranging from < 2 × 103 to 123.0 × 106 copies/gram. The multivariate linear regression analysis showed that cccDNA was independently correlated with the HBV e antigen (p < 0.001) and serum HBV-DNA levels (p = 0.012). The Cox proportional hazard model analysis showed that cccDNA independently predicted overall survival (p = 0.003) and extrahepatic metastasis-free survival (p = 0.001). In virologically suppressed HCC patients, cccDNA still effectively predicted intrahepatic recurrence-free (p = 0.003) and extrahepatic metastasis-free (p = 0.009) survivals. In conclusion, cccDNA independently predicted postoperative extrahepatic metastasis-free survival.
Collapse
Affiliation(s)
- Chao-Wei Hsu
- Liver Research Center, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan; (C.-W.H.); (Y.-D.C.); (M.-W.L.); (Y.-H.L.)
- Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
| | - Yu-De Chu
- Liver Research Center, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan; (C.-W.H.); (Y.-D.C.); (M.-W.L.); (Y.-H.L.)
| | - Ming-Wei Lai
- Liver Research Center, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan; (C.-W.H.); (Y.-D.C.); (M.-W.L.); (Y.-H.L.)
- Division of Pediatric Gastroenterology, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
| | - Chih-Lang Lin
- Liver Research Unit, Chang Gung Memorial Hospital, Keelung 204, Taiwan;
| | - Kung-Hao Liang
- Medical Research Department, Taipei Veterans General Hospital, Taipei 112, Taiwan;
| | - Yang-Hsiang Lin
- Liver Research Center, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan; (C.-W.H.); (Y.-D.C.); (M.-W.L.); (Y.-H.L.)
| | - Chau-Ting Yeh
- Liver Research Center, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan; (C.-W.H.); (Y.-D.C.); (M.-W.L.); (Y.-H.L.)
- Molecular Medicine Research Center, Chang Gung University, Taoyuan 333, Taiwan
- Correspondence: ; Tel.: +886-3-3281200 (ext. 8129)
| |
Collapse
|
|
32
|
Saboor Soomro R, Shah IA, Saboor A, Bhutto AUB, Memon S. Sensitivity and Specificity of Hepatitis B Virus Screening via Rapid Immunoassay Chromatographic Test. Cureus 2021; 13:e12909. [PMID: 33654594 PMCID: PMC7906272 DOI: 10.7759/cureus.12909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Introduction: In low-income and high hepatitis B and C virus burden countries like Pakistan, it is important to develop cheap yet efficient strategies in diagnosing as well as treating hepatitis. The aim of this study is to assess the sensitivity and specificity of serum hepatitis B surface antigen (HbsAg) via Rapid Immunoassay Chromatographic Test (RICT) for the screening of hepatitis B, compared to the gold standard laboratory-based method. Methods: The study was conducted in the Hepatology Clinic of Civil Hospital, Sukkur. All records of the clinic from June 1, 2018, to December 31, 2018, were accessed for identification of the records in which hepatitis B screening via RICT and then confirmatory polymerase chair reaction (PCR) by gene amplification with forward and reverse primers was done. Results: There were 151 samples in this study. There were 32 (94.1%) true-positive and three (5.8%) false-negative samples. There were two (2.5%) false-positive and 114 (97.4%) true-negative samples. The sensitivity of HbsAg detection via RICT for the screening of 1-1B V was 91.43%, specificity was 98.28% and the accuracy was 96.69%, compared to PCR. Conclusion: The RICT method has high sensitivity and specificity. In low-income and high-hepatitis B virus-burden countries like Pakistan, it serves as a very efficient screening tool that is easy to use, cheaper in cost, and gives rapid and accurate results.
Collapse
Affiliation(s)
| | - Iftikhar Ali Shah
- Internal Medicine, Ghulam Muhammad Mahar Medical College Hospital, Sukkur, PAK
| | - Abdul Saboor
- Urology, Ghulam Muhammad Mahar Medical College Hospital, Sukkur, PAK
| | | | - Sidra Memon
- Internal Medicine, Jinnah Sindh Medical University, Karachi, PAK
| |
Collapse
|
|
33
|
Wang X, Chi X, Wu R, Xu H, Gao X, Yu L, Liu L, Zhang M, Tan Y, Niu J, Jin Q. Serum HBV RNA correlated with intrahepatic cccDNA more strongly than other HBV markers during peg-interferon treatment. Virol J 2021; 18:4. [PMID: 33407619 PMCID: PMC7789711 DOI: 10.1186/s12985-020-01471-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Accepted: 12/15/2020] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Serum hepatitis B virus RNA (HBV RNA) has been reported to be a surrogate marker of intrahepatic cccDNA during nucleos(t)ide analogs therapy. However, in HBeAg-positive patients treated with peg-interferon (peg-IFN), whether HBV RNA is superior to other HBV markers in reflecting cccDNA profile is still unclear. METHODS Serum HBV RNA, HBcrAg, HBV DNA, and HBsAg were longitudinally assessed among 30 HBeAg-positive patients during 48-week peg-IFN treatment. Besides, intrahepatic cccDNA was detected at baseline and week 48 respectively. Then, the individual correlations between HBV RNA, HBcrAg, HBV DNA, HBsAg, and cccDNA were statistically analyzed. RESULTS HBV RNA levels decreased more rapidly in patients with HBeAg seroconversion than those without HBeAg seroconversion. Among all patients, cccDNA correlated better with HBV RNA than with HBcrAg, HBV DNA, and HBsAg at baseline. After 48 weeks peg-IFN treatment, cccDNA still correlated more strongly with HBV RNA than other HBV markers. Further analysis indicated that in patients with HBeAg seroconversion cccDNA strongly correlated with HBV RNA and HBcrAg, whereas not correlate with HBV DNA and HBsAg. While in patients without HBeAg seroconversion, cccDNA highly correlated with HBV RNA and HBV DNA, moderately correlated with HBcrAg, and not correlated with HBsAg. CONCLUSION Compared to HBcrAg, HBV DNA, and HBsAg, serum HBV RNA correlated more strongly with intrahepatic cccDNA levels before and after 48-week peg-IFN treatment. The level of serum HBV RNA may be a superior surrogate marker in reflecting the intrahepatic cccDNA profile in HBeAg-positive patients during peg-IFN treatment. Trial registration ClinicalTrials, NCT03546530. Registered 1 January 2015. https://clinicaltrials.gov/ct2/results?cond=&term=NCT03546530 .
Collapse
Affiliation(s)
- Xiaomei Wang
- Department of Hepatology, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, Jilin Province, China
| | - Xiumei Chi
- Department of Hepatology, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, Jilin Province, China
| | - Ruihong Wu
- Department of Hepatology, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, Jilin Province, China
| | - Hongqin Xu
- Department of Hepatology, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, Jilin Province, China
| | - Xiuzhu Gao
- Department of Hepatology, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, Jilin Province, China
| | - Lei Yu
- Department of Infectious Diseases, The Fourth Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, China
| | - Longgen Liu
- Department of Infectious Diseases, The Third Hospital of Changzhou, Changzhou, 213001, Jiangsu Province, China
| | - Mingxiang Zhang
- Department of Hepatology, Shenyang Sixth People's Hospital, Shenyang, 110006, Liaoning Province, China
| | - Youwen Tan
- Department of Hepatology, The Third People's Hospital of Zhenjiang, Zhenjiang, 212021, Jiangsu Province, China
| | - Junqi Niu
- Department of Hepatology, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, Jilin Province, China
| | - Qinglong Jin
- Department of Hepatology, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, Jilin Province, China.
| |
Collapse
|
|
34
|
Xia C, Tang W, Geng P, Zhu H, Zhou W, Huang H, Zhou P, Shi X. Baicalin down-regulating hepatitis B virus transcription depends on the liver-specific HNF4α-HNF1α axis. Toxicol Appl Pharmacol 2020; 403:115131. [PMID: 32687838 DOI: 10.1016/j.taap.2020.115131] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 06/06/2020] [Accepted: 07/02/2020] [Indexed: 02/07/2023]
Abstract
Baicalin (BA) inhibits hepatitis B virus (HBV) RNAs production and reduces levels of the related hepatocyte nuclear factors (HNFs), although the underlying mechanism is unclear. In this study, we investigated the specific pathway by which BA regulates HBV transcription through the HBV-related HNFs. Following transfection of HepG2 cells with pHBV1.2, we observed that BA inhibited the production of HBV RNAs and viral proteins in a time- and dose-dependent manner. These effects were consistent with the downregulation of HNF1α, which was abolished by HNF1α-shRNA. The shRNA of HNF4α, the upstream gene of HNF1α, also remarkedly reduced HNF1α expression and impaired the anti-HBV efficacy of BA, indicating that this function of BA depended on HNF4α/HNF1α axis. Furthermore, chromatin immunoprecipitation assay showed that BA significantly reduced HNF4α-HNF1α transactivation activity. The similar effects of BA were observed in entecavir (ETV)-resistant HBVrtM204V/rtLl80M transfected HepG2 cells. Thus, we proposed a mechanism for the anti-HBV activity of BA in an HNF4α-HNF1α-dependent manner, which impaired HNF4α and HNF1α transactivation, and effectively inhibited HBV transcription and viral replication.
Collapse
Affiliation(s)
- Chengjie Xia
- Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, School of Pharmacy, Fudan University, Shanghai 201203, PR China
| | - Wenyi Tang
- Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, School of Pharmacy, Fudan University, Shanghai 201203, PR China
| | - Ping Geng
- Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, School of Pharmacy, Fudan University, Shanghai 201203, PR China
| | - Haiyan Zhu
- Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, School of Pharmacy, Fudan University, Shanghai 201203, PR China
| | - Wei Zhou
- Department of Chemistry, Fudan University, 220 Han Dan Road, Shanghai 200433, PR China
| | - Hai Huang
- Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, School of Pharmacy, Fudan University, Shanghai 201203, PR China
| | - Pei Zhou
- Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, School of Pharmacy, Fudan University, Shanghai 201203, PR China
| | - Xunlong Shi
- Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, School of Pharmacy, Fudan University, Shanghai 201203, PR China.
| |
Collapse
|
|
35
|
Hepatitis B surface antigen seroclearance: Immune mechanisms, clinical impact, importance for drug development. J Hepatol 2020; 73:409-422. [PMID: 32333923 DOI: 10.1016/j.jhep.2020.04.013] [Citation(s) in RCA: 102] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Revised: 04/03/2020] [Accepted: 04/07/2020] [Indexed: 12/16/2022]
Abstract
HBsAg seroclearance occurs rarely in the natural history of chronic hepatitis B (CHB) infection and is associated with improved clinical outcomes. Many factors are associated with HBsAg seroconversion, including immune and viral factors. However, the immune mechanisms associated with HBsAg seroclearance are still difficult to elucidate. HBsAg seroclearance is the ideal aim of HBV treatment. Unfortunately, this goal is rarely achieved with current treatments. Understanding the mechanisms of HBsAg loss appears to be important for the development of curative HBV treatments. While studies from animal models give insights into the potential immune mechanisms and interactions occurring between the immune system and HBsAg, they do not recapitulate all features of CHB in humans and are subject to variability due to their complexity. In this article, we review recent studies on these immune factors, focusing on their influence on CHB progression and HBsAg seroconversion. These data provide new insights for the development of therapeutic approaches to partially restore the anti-HBV immune response. Targeting HBsAg will ideally relieve the immunosuppressive effects on the immune system and help to restore anti-HBV immune responses.
Collapse
|
|
36
|
Wang Y, Wang M, Zhang G, Ou X, Ma H, You H, Jia J. Control of Chronic Hepatitis B in China: Perspective of Diagnosis and Treatment. China CDC Wkly 2020; 2:596-600. [PMID: 34594716 PMCID: PMC8428426 DOI: 10.46234/ccdcw2020.159] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 07/18/2020] [Indexed: 01/01/2023] Open
Affiliation(s)
- Yu Wang
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Min Wang
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Guanhua Zhang
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Xiaojuan Ou
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Hong Ma
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Hong You
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Diseases, Beijing, China
| |
Collapse
|
|
37
|
Abstract
Currently, despite the use of a preventive vaccine for several decades as well as the use of effective and well-tolerated viral suppressive medications since 1998, approximately 250 million people remain infected with the virus that causes hepatitis B worldwide. Hepatitis C virus (HCV) and hepatitis B virus (HBV) are the leading causes of liver cancer and overall mortality globally, surpassing malaria and tuberculosis. Linkage to care is estimated to be very poor both in developing countries and in high-income countries, such as the United States, countries in Western Europe, and Japan. In the United States, by CDC estimates, only one-third of HBV-infected patients or less are aware of their infection. Some reasons for these low rates of surveillance, diagnosis, and treatment include the asymptomatic nature of chronic hepatitis B until the very late stages, a lack of curative therapy with a finite treatment duration, a complex natural history, and a lack of knowledge about the disease by both care providers and patients. In the last 5 years, more attention has been focused on the important topics of HBV screening, diagnosis of HBV infection, and appropriate linkage to care. There have also been rapid clinical developments toward a functional cure of HBV infection, with novel compounds currently being in various phases of progress. Despite this knowledge, many of the professional organizations provide guidelines focused only on specific questions related to the treatment of HBV infection. This focus leaves a gap for care providers on the other HBV-related issues, which include HBV's epidemiological profile, its natural history, how it interacts with other viral hepatitis diseases, treatments, and the areas that still need to be addressed in order to achieve HBV elimination by 2030. Thus, to fill these gaps and provide a more comprehensive and relevant document to regions worldwide, we have taken a global approach by using the findings of global experts on HBV as well as citing major guidelines and their various approaches to addressing HBV and its disease burden.
Collapse
|
|
38
|
Role of quantitative hepatitis B surface antigen levels in predicting liver biopsy time in treatment-naive chronic hepatitis B patients. Clin Exp Hepatol 2020; 6:55-59. [PMID: 32166125 PMCID: PMC7062122 DOI: 10.5114/ceh.2020.93058] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2019] [Accepted: 12/11/2019] [Indexed: 12/13/2022] Open
Abstract
Aim of the study The quantitative hepatitis B surface antigen (qHBsAg) level indicates the amount of transcriptional activity of covalently closed circular DNA (cccDNA) and integrated DNA in hepatocytes which plays a role in development of chronic hepatitis B (CHB) and may help decide whether the treatment is necessary or not. The aim of this study is to evaluate the association between serum qHBsAg levels and viral replication and stage of liver fibrosis in treatment-naive CHB patients and to determine the role of qHBsAg levels in predicting when liver biopsy is necessary. Material and methods 967 patients were included in the study. Because of refusal of liver biopsy the study was conducted on 123 patients. The association between qHBsAg levels with HBV DNA, a-fetoprotein, fibrosis stage and histology activity index was evaluated. Results Of the patients, mean age was 48 ±11.2 years and 56.1% were male. We found that patients with HBV DNA ≥ 2000 IU/ml had a higher qHBsAg titer in comparison with HBV DNA < 2000 IU/ml. However, there was no relationship between qHBsAg titer and liver necroinflammation or fibrosis stage. Conclusions Monitoring of qHBsAg together with HBV DNA may be helpful in CHB management. However, qHBsAg level does not provide knowledge about the timing of biopsy or the decision of CHB treatment.
Collapse
|
|
39
|
Lee HW, Chan HLY. Unresolved issues of immune tolerance in chronic hepatitis B. J Gastroenterol 2020; 55:383-389. [PMID: 32016713 PMCID: PMC7080668 DOI: 10.1007/s00535-020-01665-z] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2019] [Accepted: 01/07/2020] [Indexed: 02/07/2023]
Abstract
During the natural course of chronic hepatitis B virus infection, immune-tolerant phase is characterized by high viral replication, the presence of HBV e antigen (HBeAg), and normal or minimally elevated serum alanine aminotransferase. Immune-tolerant phase is usually regarded as a benign course of the disease. International guidelines recommend observation rather than treatment during immune-tolerant phase. In this article, we review unresolved issues related to the definition of true immune-tolerant phase and the benefit of antiviral treatment. Defining true immune-tolerant phase requires a careful approach and long-term follow-up. In previous studies, many patients were misclassified as being immune-tolerant phase. Noninvasive methods of assessing fibrosis are warranted for patients in the immune-tolerant phase. Yet, there has been controversy over the benefit and harm of antiviral treatment for immune-tolerant phase patients. Thus, further larger scale studies are needed to investigate the prognosis of patients in true immune-tolerant phase and their need for antiviral therapy.
Collapse
Affiliation(s)
- Hye Won Lee
- grid.10784.3a0000 0004 1937 0482Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong ,grid.10784.3a0000 0004 1937 0482Insitute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong ,grid.15444.300000 0004 0470 5454Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Henry Lik-Yuen Chan
- grid.10784.3a0000 0004 1937 0482Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong ,grid.10784.3a0000 0004 1937 0482Insitute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| |
Collapse
|
|
40
|
Chen Y, Li JJ, Chen R, Li G, Ji J. Dynamics of HBV surface antigen related end points in chronic hepatitis B infection: a systematic review and meta-analysis. Antivir Ther 2020; 25:203-215. [PMID: 32609658 DOI: 10.3851/imp3366] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/23/2020] [Indexed: 12/23/2022]
Abstract
BACKGROUND In chronic hepatitis B (CHB) treatment, hepatitis B surface antigen (HBsAg) is regarded as a promising clinical end point associated with long-term clinical outcomes. We performed a meta-analysis to characterize the dynamics and influencing factors of HBsAg. METHODS Literature search was conducted through PubMed from January 1995 to May 2015 for papers reporting HBsAg in patients receiving various antiviral treatments. We conducted weighted linear regression to select for potential influencing factors on maximum HBsAg loss percentage, and subgroup analysis to calculate the pooled estimates of maximum HBsAg loss and seroconversion percentage following treatment of interferon (IFN), nucleoside analogue (NUC) or combination therapies (NUC+IFN), respectively. Study heterogeneity was assessed through sensitivity test and I-square statistics. RESULTS We collected data from 24 papers involving 6,674 adult CHB patients. In most studies, average HBsAg level decreased during treatment but relapsed after treatment cessation, while HBsAg loss or seroconversion percentage continued to increase or remained stable after treatment cessation. No strong relationship was observed between maximum HBsAg change and its baseline level. The pooled estimates of maximum HBsAg loss percentage for IFN (5.3%, 2.7-7.9%) and NUC+IFN (5.2%, 3.1-7.4%) were significantly higher than that of NUC (0.93%, 0.29-1.6%). Higher maximum HBsAg loss percentage is associated with longer peak time. Pooled maximum HBsAg seroconversion percentage estimates were 1.6%, 0.56% and 6.2% for IFN, NUC and NUC+IFN. CONCLUSIONS With respect to HBsAg lowering, this meta-analysis confirmed the importance of longer treatment duration and addition of IFN, which revealed the potential value of immune-based therapies.
Collapse
Affiliation(s)
- Yusi Chen
- School of Pharmaceutical Sciences, Tsinghua University, Beijing, China.,Present address: Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA
| | | | - Rong Chen
- School of Pharmaceutical Sciences, Peking University, Beijing, China.,Present address: Center for Drug Evaluation, National Medical Products Administration, Beijing, China
| | - Gailing Li
- Clinical Pharmacology and Pharmacometrics, Janssen China R&D, Beijing, China
| | - Jia Ji
- Clinical Pharmacology and Pharmacometrics, Janssen China R&D, Beijing, China
| |
Collapse
|
|
41
|
Peng S, Wan Z, Liu T, Wang Y, Chen H, Li X, Du Y. Quantitative Hepatitis B Surface Antigen Predicts Hepatitis B Transmission in Infants Born to e Antigen-positive Mothers. J Clin Gastroenterol 2020; 54:76-82. [PMID: 30575631 DOI: 10.1097/mcg.0000000000001158] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
GOALS This study aimed to explore whether quantitative surface antigen [hepatitis B surface antigen (HBsAg)] can be used as a surrogate marker of hepatitis B virus (HBV) DNA to predict hepatitis B transmission before the first hepatitis vaccine dose in infants born to hepatitis B e antigen (HBeAg)-positive pregnant women. BACKGROUND Currently, HBV transmission persistently occurs worldwide, especially in infants born to e antigen (HBeAg)-positive highly viremic mothers. However, due to high cost, the extensive use of viral load testing to identify these high-risk mothers is limited. MATERIALS AND METHODS In total of 275 HBeAg-positive pregnant women paired with 280 infants were enrolled in this study. Quantitative HBsAg and HBV DNA levels were measured in the third trimester. Spearman rank correlation was used to assess the correlation between HBsAg levels and viral load, and multivariate logistic regression to identify factors related to HBV transmission in infants. RESULTS Among 280 infants included, 15 (5.4%) infants were infected with HBV. In this study, we observed that quantitative HBsAg was positively correlated with maternal viral load (r=0.70, P<0.001) and highly predicted HBV transmission in infants born to HBeAg-positive mothers with area under the curve of 0.76 (95% confidence interval, 0.71-0.81). The optimum threshold HBsAg levels above 4.6 log10 IU/mL to predict HBV transmission in infants had a sensitivity of 80.0%, specificity of 67.9%. CONCLUSIONS Quantitative HBsAg could be used as a surrogate marker of HBV DNA levels to predict hepatitis B transmission occurring before the injection of first-dose vaccine in infants born to e antigen-positive mothers.
Collapse
Affiliation(s)
- Songxu Peng
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology.,Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhihua Wan
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology.,Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tingting Liu
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology.,Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yanni Wang
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology.,Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hongyan Chen
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology.,Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiu Li
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology.,Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yukai Du
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology.,Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| |
Collapse
|
|
42
|
Gill US, Battisti A, Kennedy PTF. Emerging tools in the changing landscape of chronic hepatitis B management. Expert Rev Anti Infect Ther 2019; 17:943-955. [PMID: 31738607 DOI: 10.1080/14787210.2019.1694906] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Introduction: The availability of a preventative vaccine, interferon, and nucleos(t)ide analogs have provided progress in the control of chronic hepatitis B (CHB). Despite this, it remains a major contributor to global morbidity and mortality. Developments in our understanding of the pathogenesis of CHB and the emergence of new therapies are paving the way, as we move toward HBV cure.Areas covered: We performed bibliographical searches of online databases to review the literature regarding conventional disease phases of CHB. We provide the latest evidence challenging the perception of the natural history of CHB, noting that previously considered quiescent disease phases may not represent benign disease states devoid of progression. We explore the use of potential novel immunological and viral tools which should enhance disease stratification and management decisions in the coming years. Finally, we discuss the timing of treatment and how this could be initiated earlier to improve treatment outcomes, preventing sequelae of chronic infection.Expert opinion: The treatment paradigm in CHB is set to change with multiple novel agents in early phase clinical trials with the aim of a functional cure. An improved understanding of disease pathogenesis and the timing of treatment will be critical to the success of new therapies.
Collapse
Affiliation(s)
- Upkar S Gill
- Barts Liver Centre, Centre for Immunobiology, Blizard Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, UK
| | - Arianna Battisti
- Barts Liver Centre, Centre for Immunobiology, Blizard Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, UK
| | - Patrick T F Kennedy
- Barts Liver Centre, Centre for Immunobiology, Blizard Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, UK
| |
Collapse
|
|
43
|
Targets and future direct-acting antiviral approaches to achieve hepatitis B virus cure. Lancet Gastroenterol Hepatol 2019; 4:883-892. [DOI: 10.1016/s2468-1253(19)30190-6] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Revised: 05/06/2019] [Accepted: 05/14/2019] [Indexed: 12/13/2022]
|
|
44
|
Liu S, Xin Y. HBV cccDNA: The Stumbling Block for Treatment of HBV Infection. J Clin Transl Hepatol 2019; 7:195-196. [PMID: 31608210 PMCID: PMC6783674 DOI: 10.14218/jcth.2019.00047] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2019] [Revised: 09/20/2019] [Accepted: 09/20/2019] [Indexed: 12/17/2022] Open
Affiliation(s)
- Shousheng Liu
- Central Laboratories, Qingdao Municipal Hospital, Qingdao, China
| | - Yongning Xin
- Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao, China
- Correspondence to: Yongning Xin, Department of Infectious Disease, Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao, Shandong 266011, China. Tel: +86-532-82789463, Fax: +86-532-85968434, E-mail:
| |
Collapse
|
|
45
|
Svicher V, Salpini R, Malagnino V, Piermatteo L, Alkhatib M, Cerva C, Sarmati L. New Markers in Monitoring the Reactivation of Hepatitis B Virus Infection in Immunocompromised Hosts. Viruses 2019; 11:v11090783. [PMID: 31450680 PMCID: PMC6784136 DOI: 10.3390/v11090783] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2019] [Revised: 08/21/2019] [Accepted: 08/23/2019] [Indexed: 02/07/2023] Open
Abstract
Hepatitis B virus (HBV) persistence is at the basis of HBV reactivation as a consequence of chemotherapy and immunosuppressive treatments. The identification of early viral replication indicators and markers of effective HBV immunological control would be useful in monitoring patients who are at risk of potential viral reactivation during the course of immunosuppressive treatment. Currently, international guidelines have shared some criteria to identify patients with a low, medium or high risk of HBV reactivation; however, permanently placing a patient in a definitive category is not always easy. More often, patients move from one category to another during the course of their immunosuppressive treatment; therefore, in many cases, there are no precise indicators or tools for monitoring possible reactivation and establishing the duration and suspension of antiviral prophylaxis. Historically, the sequence of HBV antigens and antibodies and HBV DNA levels has been used to evaluate the different stages of the acute and chronic phases of an HBV infection. In the last few years, new biomarkers, such as anti-HBs and anti-HBc titres, HBV core-related antigen (HBcrAg), ultra-sensitive HBsAg evaluation and HBV RNA, have been used in patients with an HBV infection to evaluate their diagnostic and prognostic potential. The aim of this review is to evaluate the published results on the use of new infection markers in the diagnosis and monitoring of HBV reactivation over the course of immunosuppressive treatments. Moreover, the importance of viral genotypic studies was emphasized, given the diagnostic and therapeutic implications of the mutational profiles of HBsAg during the HBV reactivation phase.
Collapse
Affiliation(s)
- Valentina Svicher
- Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, 00133 Rome, Italy
| | - Romina Salpini
- Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, 00133 Rome, Italy
| | - Vincenzo Malagnino
- Clinic of Infectious Diseases, Department of System Medicine, University of Rome Tor Vergata, 00133 Rome, Italy
| | - Lorenzo Piermatteo
- Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, 00133 Rome, Italy
| | - Mohammad Alkhatib
- Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, 00133 Rome, Italy
| | - Carlotta Cerva
- Clinic of Infectious Diseases, Department of System Medicine, University of Rome Tor Vergata, 00133 Rome, Italy
| | - Loredana Sarmati
- Clinic of Infectious Diseases, Department of System Medicine, University of Rome Tor Vergata, 00133 Rome, Italy.
| |
Collapse
|
|
46
|
Charre C, Levrero M, Zoulim F, Scholtès C. Non-invasive biomarkers for chronic hepatitis B virus infection management. Antiviral Res 2019; 169:104553. [PMID: 31288041 DOI: 10.1016/j.antiviral.2019.104553] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Revised: 07/05/2019] [Accepted: 07/05/2019] [Indexed: 12/12/2022]
Abstract
Chronic hepatitis B virus (HBV) infection remains a major health burden with over 250 million cases worldwide. This complex infection can lead to chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Complete recovery is seldom achieved due to the persistence in infected hepatocytes of covalently closed circular (ccc)DNA, which is not targeted by current antiviral therapies. Routine circulating biomarkers used for clinical monitoring of patients do not accurately reflect the cccDNA pool and transcriptional activity. New biomarkers, such as serum HB core-related Ag and circulating HBV RNAs, are under development. In this review, we discuss surrogate non-invasive biomarkers for evaluating intrahepatic cccDNA abundance and transcriptional activity. We also present their relevance for improving the classification of patients with regards to their natural history and for evaluating novel compounds to assess target engagement and to define new virological endpoints.
Collapse
Affiliation(s)
- Caroline Charre
- INSERM U1052-Cancer Research Center of Lyon (CRCL), 69008, Lyon, France; University of Lyon, University Claude Bernard Lyon 1 (UCBL1), Lyon, France; Department of Virology, Croix Rousse Hospital, Hospices Civils de Lyon, Lyon, France
| | - Massimo Levrero
- INSERM U1052-Cancer Research Center of Lyon (CRCL), 69008, Lyon, France; University of Lyon, University Claude Bernard Lyon 1 (UCBL1), Lyon, France; Department of Hepatology, Croix Rousse Hospital, Hospices Civils de Lyon, Lyon, France
| | - Fabien Zoulim
- INSERM U1052-Cancer Research Center of Lyon (CRCL), 69008, Lyon, France; University of Lyon, University Claude Bernard Lyon 1 (UCBL1), Lyon, France; Department of Hepatology, Croix Rousse Hospital, Hospices Civils de Lyon, Lyon, France
| | - Caroline Scholtès
- INSERM U1052-Cancer Research Center of Lyon (CRCL), 69008, Lyon, France; University of Lyon, University Claude Bernard Lyon 1 (UCBL1), Lyon, France; Department of Virology, Croix Rousse Hospital, Hospices Civils de Lyon, Lyon, France.
| |
Collapse
|
|
47
|
Akindigh TM, Joseph AO, Robert CO, Okojokwu OJ, Okechalu JN, Anejo-Okopi JA. Seroprevalence of hepatitis B virus co-infection among HIV-1-positive patients in North-Central Nigeria: The urgent need for surveillance. Afr J Lab Med 2019; 8:622. [PMID: 31309044 PMCID: PMC6620520 DOI: 10.4102/ajlm.v8i1.622] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2017] [Accepted: 12/04/2018] [Indexed: 12/23/2022] Open
Abstract
We report the seroprevalence of hepatitis B surface antigen among HIV-positive patients at a clinic in North-Central Nigeria. Screening for hepatitis B virus was based on serological markers. Alanine aminotransferase levels and CD4+ T-lymphocyte counts were compared between patients. The study showed that 9.2% were positive for hepatitis B surface antigen with significant differences between alanine aminotransferase levels of patients with and without hepatitis B virus. We recommend a national surveillance system to monitor control efforts.
Collapse
Affiliation(s)
- Terver M Akindigh
- Infectious Diseases Unit, Jos University Teaching Hospital, Jos, Nigeria
| | - Abba O Joseph
- Infectious Diseases Unit, Jos University Teaching Hospital, Jos, Nigeria
| | - Christiana O Robert
- Department of Microbiology, Faculty of Natural Sciences, University of Jos, Jos, Nigeria
| | - Ocheme J Okojokwu
- Department of Microbiology, Faculty of Natural Sciences, University of Jos, Jos, Nigeria
| | - Juliet N Okechalu
- Department of Microbiology, Faculty of Natural Sciences, University of Jos, Jos, Nigeria
| | - Joseph A Anejo-Okopi
- Department of Microbiology, Faculty of Natural Sciences, University of Jos, Jos, Nigeria
| |
Collapse
|
|
48
|
KASL clinical practice guidelines for management of chronic hepatitis B. Clin Mol Hepatol 2019; 25:93-159. [PMID: 31185710 PMCID: PMC6589848 DOI: 10.3350/cmh.2019.1002] [Citation(s) in RCA: 165] [Impact Index Per Article: 27.5] [Reference Citation Analysis] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Accepted: 03/25/2019] [Indexed: 02/06/2023] Open
|
|
49
|
Abd El Moety HA, Maharem DA, Gomaa SH. Serotonin: is it a marker for the diagnosis of hepatocellular carcinoma in cirrhotic patients? ALEXANDRIA JOURNAL OF MEDICINE 2019. [DOI: 10.1016/j.ajme.2013.03.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Affiliation(s)
- Hoda Aly Abd El Moety
- Chemical Pathology, Medical Research Institute , Alexandria University , 16 Alexander the Great , Azarita, Alexandria, Egypt
| | - Dalia Aly Maharem
- Internal Medicine, Medical Research Institute , Alexandria University , 16 Alexander the Great , Azarita, Alexandria, Egypt
| | - Salwa Hamdy Gomaa
- Chemical Pathology, Medical Research Institute , Alexandria University , 16 Alexander the Great , Azarita, Alexandria, Egypt
| |
Collapse
|
|
50
|
Evaluation of serum nitric oxide before and after local radiofrequency thermal ablation for hepatocellular carcinoma. ALEXANDRIA JOURNAL OF MEDICINE 2019. [DOI: 10.1016/j.ajme.2012.08.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
|