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Wu Y, Tang G, Wen J, Wan Y, Wang Y, Li L. Serum hepatitis B virus RNA in low-level viremia of chronic hepatitis B: clinical features and association with virological response. Virol J 2025; 22:132. [PMID: 40325459 PMCID: PMC12054217 DOI: 10.1186/s12985-025-02712-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 03/21/2025] [Indexed: 05/07/2025] Open
Abstract
BACKGROUND The role of hepatitis B virus (HBV) RNA in the management of patients with chronic hepatitis B (CHB) experienced with low-level viremia (LLV) remains poorly defined. This study was designed to evaluate the prognostic utility of serum HBV RNA as a biomarker for predicting treatment outcomes in this population. METHODS A retrospective cohort analysis was conducted on 117 pediatric patients with LLV (mean age: 13.14 years; 34% female) treated with continuous entecavir (ConT) or modified regimens (switching to or combining with tenofovir disoproxil fumarate) for ≥ 120 weeks. Virological response was defined as HBV DNA < 10 IU/mL at week 120. RESULTS No significant baseline differences existed between ConT and modified regimen groups. Compared to ConT, modified regimens achieved greater reductions in serum HBV DNA, HBV RNA, and quantitative HBsAg, with higher cumulative undetectable rates at week 120 (HBV DNA: ≥ 80.0%; HBV RNA: ≥ 54.8%; P < 0.05). Notably, qHBsAg levels remained elevated in most patients, with only 3 individuals achieving undetectable levels (< 0.05 IU/mL). Multivariate analysis identified higher HBV RNA levels at week 48 as an independent risk factor for non-virological response (adjusted odds ratio: 5.86; 95% confidence interval: 1.40-24.62; P = 0.016). Although HBV RNA alone was less predictive than HBV DNA (area under the receiver operating characteristic curve [AUC]: 0.76 vs. 0.80; P = 0.459), combining both markers improved prediction accuracy (AUC: 0.82; P < 0.05 vs. single markers). CONCLUSIONS In children with LLV, serum HBV RNA level is an independent risk factor for non-virological response and may serve as a complementary biomarker to HBV DNA for guiding antiviral therapy adjustments.
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Affiliation(s)
- Yongbin Wu
- Department of Laboratory Medicine, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin, China.
| | - Guifang Tang
- Department of Infectious Diseases, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin, China
| | - Jian Wen
- Department of Hematology, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin, China
| | - Ying Wan
- Department of Laboratory Medicine, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin, China
| | - Yufei Wang
- Department of Clinical Diagnosis, Laboratory of Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Ling Li
- School of Basic Medical Science, Southern Medical University, Guangzhou, China
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Huang J, Li X, You L, Chong Y, Cao H. Relationship Between Nucleos(t)ide analogue antiviral response time and prognosis in Chronic Hepatitis B: conclusions depend on baseline viral load and HBeAg status. Front Pharmacol 2025; 16:1572827. [PMID: 40343009 PMCID: PMC12058476 DOI: 10.3389/fphar.2025.1572827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Accepted: 04/10/2025] [Indexed: 05/11/2025] Open
Abstract
Introduction Current guidelines for changing antiviral therapy regimens do not consider different baseline statuses. This study aimed to investigate whether significant prognostic differences exist among patients achieving virological response at various time points and whether these differences vary by viral load and HBeAg status. Methods This retrospective cohort study included 1,037 patients, who were classified based on their baseline viral load (high viral load, HVL, ≥ 7log10 IU mL-1: 522 individuals; or non-HVL, < 7log10 IU mL-1: 515 individuals) and HBeAg status (positive: 668 individuals; or negative: 369 individuals). Based on the virological response time, patients were grouped separately using 48 weeks and 96 weeks as the boundaries. The prognoses across these groups were evaluated and compared. Results Patients in the within-48-week group, 48-96-week group, and after-96-week group exhibited no significant difference in the incidence of liver disease progression (5.08% vs 4.38% vs 9.61%, p = 0.33). For HVL or HBeAg-positive patients, there was no significant difference in the cumulative incidence of liver disease progression between the within-48-week group and the 48-96-week group. In contrast, for non-HVL or HBeAg-negative patients, the cumulative incidence of liver disease progression was significantly higher in the after-48-week group than in the within-48-week group. Only the after-96-week group showed a significant increase in maintained virological response rate (p = 0.04). Conclusion Antiviral treatment should be adjusted at 48 weeks for non-HVL or HBeAg-negative patients. For HVL and HBeAg-positive patients, we suggest changing the antiviral treatment plan to 96 weeks.
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Affiliation(s)
| | | | | | - Yutian Chong
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, China
| | - Hong Cao
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, China
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Li R, Li W, Yang Q, Guan Y, Chen Y, Zhu P, Su K, Li Q, Hu X, Zang M, Zhao M, Zhong M, Yan J, Yang K, Zhu W, Lin Z, Yuan G, Chen J. Low-Level Viremia Impairs Efficacy of Immune Checkpoint Inhibitors in Unresectable Hepatocellular Carcinoma. Liver Int 2025; 45:e70066. [PMID: 40078069 PMCID: PMC11904444 DOI: 10.1111/liv.70066] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2024] [Revised: 02/27/2025] [Accepted: 03/05/2025] [Indexed: 03/14/2025]
Abstract
BACKGROUND AND AIMS The impact of low-level viremia(LLV) on the efficacy of immune checkpoint inhibitors (ICIs) in unresectable hepatocellular carcinoma(uHCC) patients remains unclear. This study aims to investigate the effect of LLV on the outcomes of ICIs-based therapy in patients with uHCC. METHODS In this multicenter retrospective study, we included patients with uHCC who received ICIs-based therapy at four centres between January 2019 and December 2022. All patients were positive for HBsAg and were on nucleos(t)ide analogues (NAs) antiviral therapy. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to balance baseline characteristics between the LLV and maintained virological response (MVR) groups. Proteomic analysis was performed on a subset of patients to identify differential protein expression. RESULTS A total of 329 patients (mean age 56 years; 92.4% male; 70.8% BCLC stage C) were included, with 170 patients in the LLV group and 159 in the MVR group. The objective response rate (ORR) was significantly lower in the LLV group compared to the MVR group (21.2% vs. 36.5%, p = 0.002), as was the disease control rate (DCR) (78.8% vs. 92.5%, p < 0.001). Median progression-free survival (mPFS) was shorter in the LLV group (7.6 vs. 12.6 months, p < 0.001), as was median overall survival (mOS) (22.8 vs. 40.0 months, p < 0.001). These differences remained consistent after PSM and IPTW adjustments. Multivariate analysis identified LLV as the only independent risk factor for overall survival (hazard ratio [HR] 0.522, 95% CI 0.348-0.781; p = 0.002). Proteomic analysis revealed significant differences in the expression of Flt3L, SLAMF1 and FGF-5 proteins between the LLV and MVR groups. CONCLUSION LLV is associated with poorer responses to ICIs-based therapy and reduced survival in patients with HBV-related uHCC.
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Affiliation(s)
- Rong Li
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious DiseasesNanfang Hospital, Southern Medical UniversityGuangzhouGuangdongPeople's Republic of China
- Department of Respiratory MedicineThe Third People's Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong UniversityChengduSichuanPeople's Republic of China
| | - Wenli Li
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious DiseasesNanfang Hospital, Southern Medical UniversityGuangzhouGuangdongPeople's Republic of China
| | - Qing Yang
- Department of Infectious DiseasesZhuhai People's HospitalZhuhaiGuangdongPeople's Republic of China
| | - Yujuan Guan
- Department of HepatologyGuangzhou Eighth People's Hospital Affiliated to Guangzhou Medical UniversityGuangzhouGuangdongPeople's Republic of China
| | - Yongru Chen
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious DiseasesNanfang Hospital, Southern Medical UniversityGuangzhouGuangdongPeople's Republic of China
| | - Peilin Zhu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious DiseasesNanfang Hospital, Southern Medical UniversityGuangzhouGuangdongPeople's Republic of China
| | - Kaiyan Su
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious DiseasesNanfang Hospital, Southern Medical UniversityGuangzhouGuangdongPeople's Republic of China
| | - Qi Li
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious DiseasesNanfang Hospital, Southern Medical UniversityGuangzhouGuangdongPeople's Republic of China
| | - Xiaoyun Hu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious DiseasesNanfang Hospital, Southern Medical UniversityGuangzhouGuangdongPeople's Republic of China
| | - Mengya Zang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious DiseasesNanfang Hospital, Southern Medical UniversityGuangzhouGuangdongPeople's Republic of China
| | - Miaoxian Zhao
- Department of Infectious DiseasesZhuhai People's HospitalZhuhaiGuangdongPeople's Republic of China
| | - Manhua Zhong
- Department of Infectious DiseasesZhuhai People's HospitalZhuhaiGuangdongPeople's Republic of China
| | - Jingquan Yan
- Department of HepatologyHuizhou Central People's HospitalHuizhouGuangdongPeople's Republic of China
| | - Keli Yang
- Department of HepatologyGuangzhou Eighth People's Hospital Affiliated to Guangzhou Medical UniversityGuangzhouGuangdongPeople's Republic of China
| | - Wei Zhu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious DiseasesNanfang Hospital, Southern Medical UniversityGuangzhouGuangdongPeople's Republic of China
| | - Zhanzhou Lin
- Department of HepatologyHuizhou Central People's HospitalHuizhouGuangdongPeople's Republic of China
| | - Guosheng Yuan
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious DiseasesNanfang Hospital, Southern Medical UniversityGuangzhouGuangdongPeople's Republic of China
| | - Jinzhang Chen
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious DiseasesNanfang Hospital, Southern Medical UniversityGuangzhouGuangdongPeople's Republic of China
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Wu D, Kao JH, Piratvisuth T, Wang X, Kennedy PT, Otsuka M, Ahn SH, Tanaka Y, Wang G, Yuan Z, Li W, Lim YS, Niu J, Lu F, Zhang W, Gao Z, Kaewdech A, Han M, Yan W, Ren H, Hu P, Shu S, Kwo PY, Wang FS, Yuen MF, Ning Q. Update on the treatment navigation for functional cure of chronic hepatitis B: Expert consensus 2.0. Clin Mol Hepatol 2025; 31:S134-S164. [PMID: 39838828 PMCID: PMC11925436 DOI: 10.3350/cmh.2024.0780] [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: 09/09/2024] [Revised: 01/18/2025] [Accepted: 01/21/2025] [Indexed: 01/23/2025] Open
Abstract
As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.
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Affiliation(s)
- Di Wu
- Department of Infectious Diseases, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology, Wuhan, China
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Teerha Piratvisuth
- NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand
| | - Xiaojing Wang
- Department of Infectious Diseases, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology, Wuhan, China
| | - Patrick T.F. Kennedy
- Barts Liver Centre, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Motoyuki Otsuka
- Department of Gastroenterology and Hepatology, Academic Fields of Medicine, Dentistry, and Pharmaceutical Science, Okayama University, Okayama, Japan
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Yasuhito Tanaka
- Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Guiqiang Wang
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China
| | - Zhenghong Yuan
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Wenhui Li
- National Institute of Biological Sciences, Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China
| | - Young-Suk Lim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Junqi Niu
- Department of Hepatology, First Hospital of Jilin University, Jilin University, Jilin, China
| | - Fengmin Lu
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Wenhong Zhang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zhiliang Gao
- Department of Infectious Diseases, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Apichat Kaewdech
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | - Meifang Han
- Department of Infectious Diseases, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology, Wuhan, China
| | - Weiming Yan
- Department of Infectious Diseases, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology, Wuhan, China
| | - Hong Ren
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Peng Hu
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Sainan Shu
- Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Paul Yien Kwo
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford University School of Medicine, Stanford, CA, USA
| | - Fu-sheng Wang
- Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
| | - Man-Fung Yuen
- Department of Medicine, School of Clinical Medicine & State Key Laboratory of Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China
| | - Qin Ning
- Department of Infectious Diseases, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology, Wuhan, China
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Song YX, Song GJ, Ma H, Feng B, Xie YD. Long-Term Real-World Outcomes of Tenofovir Alafenamide in Chronic Hepatitis B: Detailed Analysis of Treatment-Naive and Experienced Patients. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2025; 85:64-72. [PMID: 39849813 DOI: 10.4166/kjg.2024.140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/16/2024] [Revised: 12/22/2024] [Accepted: 12/26/2024] [Indexed: 01/30/2025]
Abstract
Background/Aims This study assessed the long-term efficacy and safety of tenofovir alafenamide (TAF) in real-world settings. Methods Patients who were candidates for TAF treatment and were followed up at 12-week intervals over 192 weeks were enrolled in this study. Results One hundred and forty-four patients (50 treatment-naive and 94 treatment-experienced) were included in this study. The cumulative incidence rates of cirrhosis and hepatocellular carcinoma at 192 weeks were 3.9% and 0.7%, respectively. In treatment- naive patients, the rates of a virological response, HBeAg conversion, and HBsAg loss at 192 weeks were 100%, 33.3%, and 2%, respectively. The treatment-naive patients exhibited higher baseline HBsAg levels than the treatment-experienced patients (4.31 log10IU/mL vs. 3.97 log10IU/mL). A significant decrease in the HBsAg levels from the baseline was observed at 144 and 192 weeks in the treatment-naive patients (p=0.01). The baseline body mass index (BMI) <25 kg/m2 (p=0.02) and HBsAg <3.3 log10IU/mL (p=0.04) were identified as predictive factors for a decrease in HBsAg ≥0.5 log10IU/mL at 48 weeks. The eGFR levels were consistently lower in the treatment-experienced patients throughout the study. Although the treatment-naive patients showed no abnormal increases in urinary URBP, the treatment-experienced patients showed elevated urinary β2MG and NAG levels at the baseline, which decreased over the treatment course. The total cholesterol, triglyceride, and low-density lipoprotein levels were similar in both groups. Conclusions Prolonging the TAF treatment duration enhances the virological response rate. The decline in HBsAg levels was more significant in the treatment-naive patients than in the treatment-experienced patients. The baseline BMI <25 kg/m2 and HBsAg <3.3 log10IU/mL were predictive factors for a significant decline in HBsAg at 48 weeks. TAF has high renal safety and no significant impact on lipid levels.
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Affiliation(s)
- Yu-Xuan Song
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing, China
| | - Guang-Jun Song
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing, China
| | - Hui Ma
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing, China
| | - Bo Feng
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing, China
| | - Yan-Di Xie
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing, China
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Xing T. Existing problems and new advice on stage criteria of natural history for chronic hepatitis B. BMC Infect Dis 2025; 25:17. [PMID: 39754052 PMCID: PMC11699759 DOI: 10.1186/s12879-024-10408-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Accepted: 12/24/2024] [Indexed: 01/06/2025] Open
Abstract
The natural stages of chronic hepatitis B can be divided into four stages according to changes in virology, biochemistry, and pathology. However, there have been significant differences in the recommended stage criteria in the several major guidelines for chronic hepatitis B, especially regarding the immune tolerance phase. Inconsistent standards of indicators for different stages resulted in some problems, such as incorrect stage, uncertain stages and poor comparation of related studies. We propose suggestions for revisions to the stage criteria for CHB based on recent researches, including three stages: immune tolerance stage, immune clearance stage, and immune control stage. These revision suggestions rationalize some of the existing problems with the stage criteria for CHB and can significantly reduce the number of patients in the "uncertain stage" or "gray zone," which is particularly valuable in guiding clinical practice. However, further clinical studies with large samples are needed to confirm these suggestions.
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Affiliation(s)
- Tongjing Xing
- Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Linhai, Zhejiang Province, China.
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Li J, Liu S, Zang Q, Yang R, Zhao Y, He Y. Current trends and advances in antiviral therapy for chronic hepatitis B. Chin Med J (Engl) 2024; 137:2821-2832. [PMID: 38945693 PMCID: PMC11649291 DOI: 10.1097/cm9.0000000000003178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Indexed: 07/02/2024] Open
Abstract
ABSTRACT Chronic hepatitis B virus (HBV) infection is a global public health concern. Existing antiviral drugs, including nucleos(t)ide analogs and interferon-α, can suppress HBV replication and improve the prognosis. However, the persistence of covalently closed circular DNA (cccDNA), the integration of HBV-DNA into the host genome, and compromised immune responses impede the successful treatment of hepatitis B. While achieving a functional cure of HBV remains elusive with the current treatment methods, this is the goal of new therapeutic approaches. Therefore, developing novel antiviral drugs is necessary for achieving a functional or complete cure for chronic hepatitis B. In recent years, substantial progress has been made in drug discovery and development for HBV infection. Direct-acting antiviral agents such as entry inhibitors, capsid assembly modulators, subviral particle release inhibitors, cccDNA silencers, and RNA interference molecules have entered clinical trials. In addition, several immunomodulatory agents, including toll-like receptor agonists, therapeutic vaccines, checkpoint inhibitors, and monoclonal antibodies, are also making their way toward clinical use. In this review, we summarize the recent progress and limitations of chronic hepatitis B treatment and discuss perspectives on approaches to achieving functional cure. Although it will take some time for these new antiviral drugs to be widely used in clinical practice, combination therapy may become a preferable treatment option in the future.
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Affiliation(s)
- Juan Li
- Department of Infectious Diseases, First Affiliated Teaching Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China
- Institution of Hepatology, First Affiliated Teaching Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China
| | - Siyi Liu
- Department of Infectious Diseases, First Affiliated Teaching Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China
| | - Qijuan Zang
- Department of Infectious Diseases, First Affiliated Teaching Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China
| | - Ruijie Yang
- Institution of Hepatology, First Affiliated Teaching Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China
| | - Yingren Zhao
- Department of Infectious Diseases, First Affiliated Teaching Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China
- Institution of Hepatology, First Affiliated Teaching Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China
- Shaanxi Clinical Research Center of Infectious Diseases, Xi’an, Shaanxi 710061, China
- Clinical Research Center for Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China
| | - Yingli He
- Department of Infectious Diseases, First Affiliated Teaching Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China
- Institution of Hepatology, First Affiliated Teaching Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China
- Shaanxi Clinical Research Center of Infectious Diseases, Xi’an, Shaanxi 710061, China
- Clinical Research Center for Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China
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Lin WC, Lin K, Li MK, Liu X, Huang YF, Wang X, Wu B. Low level of hepatitis B viremia is associated with increased risk of hepatocellular carcinoma in compensated cirrhotic patients. World J Hepatol 2024; 16:1321-1330. [PMID: 39606169 PMCID: PMC11586753 DOI: 10.4254/wjh.v16.i11.1321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Revised: 09/09/2024] [Accepted: 10/10/2024] [Indexed: 11/06/2024] Open
Abstract
BACKGROUND Whether patients with compensated cirrhosis and low-level viremia (LLV) of hepatitis B should receive antiviral therapy (AVT) is still controversial, and published results are inconsistent. AIM To investigate the link between LLV in compensated cirrhosis and prognosis concerning hepatocellular carcinoma (HCC), decompensation, and liver-related events. METHODS The PubMed, EMBASE, and Cochrane Library databases were searched up to March 5, 2023. Outcomes of interest were assessed by pooled hazard ratios (HRs). The study was registered with PROSPERO (CRD42023405345). RESULTS Six cohort studies representing 3155 patients were included. Compared with patients with undetectable HBV DNA, patients with LLV was associated with increased risk of HCC (HR: 2.06, 95%CI: 1.36-3.13; Q-statistic-P = 0.07, I 2 = 51%) regardless of receiving AVT or not (AVT group: HR: 3.14; 95%CI: 1.73-5.69; Q-statistic-P = 0.60, I 2 = 0%; un-AVT group: HR: 1.73, 95%CI: 1.09-2.76; Q-statistic-P = 0.11, I 2 = 50%). The pooled results showed no statistical association between LLV and decompensation of cirrhosis (HR: 2.06, 95%CI: 0.89-4.76; Q-statistic-P = 0.04, I 2 = 69%), and liver-related events (HR: 1.84, 95%CI: 0.92-3.67; Q-statistic-P = 0.03, I 2 = 72%), respectively. Grading of Recommendations Assessment, Development and Evaluation assessment indicated moderate certainty for HCC, very low certainty for decompensation of cirrhosis and liver-related clinical events. CONCLUSION LLV in compensated cirrhotic patients is associated with increased risk of HCC, higher tendency for hepatic decompensation and liver-related events. Closer screening of HCC should be conducted in this population.
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Affiliation(s)
- Wei-Chun Lin
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Ke Lin
- Department of Medical Ultrasonics, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, Guangdong Province, China
| | - Ming-Kai Li
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Xiao Liu
- Department of Cardiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510000, Guangdong Province, China
| | - Yi-Fei Huang
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Xing Wang
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Bin Wu
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China.
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9
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Chen HM, Xia M, Zheng XF, Zheng JC. Long-term clinical outcomes of maintenance therapy with nucleos(t)ide analogues in chronic hepatitis B patients with low-level viremia: A systematic review and meta-analysis. Shijie Huaren Xiaohua Zazhi 2024; 32:686-694. [DOI: 10.11569/wcjd.v32.i9.686] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 08/26/2024] [Accepted: 09/19/2024] [Indexed: 09/28/2024] Open
Abstract
BACKGROUND For chronic hepatitis B patients who develop low-level viremia (LLV) after treatment with first-line nucleos(t)ide analogues (NAs), there is still a lack of research on the long-term clinical outcomes of continuing NAs therapy.
AIM To evaluate the long-term clinical outcomes of continuing the original NAs therapy vs switching to a different NAs regimen in patients with chronic hepatitis B experiencing LLV after first-line NAs treatment through a systematic review and meta-analysis.
METHODS Relevant studies were selected through computer searches of PubMed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases. R4.3.1 software was used for meta-analysis of the included studies.
RESULTS A total of 11 articles involving 3153 chronic hepatitis B patients with LLV were included. Among them, 7 articles conducted quantitative meta-analysis of HBV DNA seroconversion rate, indicating that the HBV DNA seroconversion rate in the group switching to a new NAs regimen after 24 wk [relative risk (RR) = 4.23, 95% confidence interval (CI): 2.47-7.24), P < 0.01] and 48 wk (RR = 2.90, 95%CI: 1.75-4.81, P < 0.01) of continued treatment was significantly higher than that of the group continuing the original NAs regimen. Six articles conducted quantitative meta-analysis of HBeAg seroconversion rate, showing that the HBeAg seroconversion rate of the group switching to a new NAs treatment regimen after 24 wk was higher than that of the group continuing the original regimen (RR = 2.31, 95%CI: 1.28-4.19, P < 0.01), but there was no significant difference between the two groups when switching occured at 48 wk (RR = 1.50, 95%CI: 0.88-2.54, P = 0.13). Qualitative systematic evaluation of the incidence of end-stage liver disease was conducted in 3 articles, showing that the LLV group continuing NAs treatment had a significantly higher incidence of long-term end-stage liver disease compared to the maintained virological response (MVR) group (P < 0.05).
CONCLUSION Switching to a new NAs regimen can improve the long-term HBV DNA and HBeAg seroconversion rates in chronic hepatitis B patients with LLV, but the incidence of end-stage liver disease in patients continuing NAs treatment is significantly higher than that of patients with MVR.
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Affiliation(s)
- He-Min Chen
- People's Hospital of Jiangshan, Jiangshan 324100, Zhejiang Province, China
| | - Ming Xia
- People's Hospital of Jiangshan, Jiangshan 324100, Zhejiang Province, China
| | - Xu-Feng Zheng
- People's Hospital of Jiangshan, Jiangshan 324100, Zhejiang Province, China
| | - Ji-Cai Zheng
- People's Hospital of Jiangshan, Jiangshan 324100, Zhejiang Province, China
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10
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Lin K, Jiang SW, Hu AR. Management of antiviral treatment for chronic hepatitis B patients with high viral load. Shijie Huaren Xiaohua Zazhi 2024; 32:625-634. [DOI: 10.11569/wcjd.v32.i9.625] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 08/30/2024] [Accepted: 09/19/2024] [Indexed: 09/28/2024] Open
Abstract
Currently, the therapeutic indications for chronic hepatitis B are expanding, and chronic hepatitis B virus (HBV) infection seemingly has entered the era of "treat-all" or "simplified treatment". In this context, there remain many unresolved issues encompassing aspects like diagnosis, treatment, and disease management. For patients with a high baseline viral load [HBV DNA > 2 × 107 IU/mL according to the Chinese Medical Association guidelines, and > 107 IU/mL according to the European Association for the Study of the Liver guidelines], following the implementation of antiviral treatment, there may exist issues such as a relatively low virological response rate and corresponding increased risks of low level viremia (LLV) and HBV drug resistance mutations. Once patients develop LLV, their liver diseases will continue to progress (including the progression of liver fibrosis, cirrhosis, and hepatocellular carcinoma). In the LLV population, how can we optimize the subsequent treatment strategy (replacement therapy or combination therapy)? What is the modality of combination therapy? How effective is the optimized treatment? Therefore, we must take precautions beforehand and remain vigilant against the potential issues that the new strategy might bring. In this paper, based on the advances in domestic and international research, we discuss the correlation between HBV DNA level and disease progression, the efficacy of antiviral therapy in patients with a high baseline viral load, the epidemiology and disease progression of LLV, and the optimization of treatment strategies for LLV, aiming to provide references for the management of antiviral therapy for hepatitis B patients with a high viral load.
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Affiliation(s)
- Ken Lin
- Health Science Center, Ningbo University, Ningbo 315211, Zhejiang Province, China
| | - Su-Wen Jiang
- Liver Diseases Center, Ningbo No. 2 Hospital, Ningbo 315010, Zhejiang Province, China
| | - Ai-Rong Hu
- Liver Diseases Center, Ningbo No. 2 Hospital, Ningbo 315010, Zhejiang Province, China
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11
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Xu J, Zhang Y, Zhu L, Tang S, Xu H, Zhang D, Chen H, Zhou J. Non-Invasive Monitoring of the Impact of Low-Level Viremia on Liver Fibrosis in Treated Chronic Hepatitis B Patients. Infect Drug Resist 2024; 17:2751-2758. [PMID: 38974312 PMCID: PMC11227854 DOI: 10.2147/idr.s463843] [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: 04/07/2024] [Accepted: 06/26/2024] [Indexed: 07/09/2024] Open
Abstract
Background Chronic hepatitis B (CHB) presents a global health challenge due to its potential to cause severe liver conditions such as hepatocellular carcinoma (HCC) and cirrhosis. Prior research has established a correlation between CHB infection with low-level viremia (LLV) and liver disease progression, such as increased HCC incidence. This study aims to investigate whether LLV during treatment with nucleos(t)ide analogs (NAs) contributes to the accelerated progression of liver fibrosis (LF). Methods This retrospective cohort study at Jinhua Central Hospital focused on CHB patients undergone NA monotherapy for over 96 weeks. Patients were categorized into maintained virological response (MVR) and LLV groups based on hepatitis B virus (HBV) DNA levels. The study assessed LF using various markers and methods, including chitinase 3-like 1 protein (CHI3L1), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 (FIB-4) score, and transient elastography. Results Analysis was conducted on 92 CHB patients, categorized into LLV (n=42) and MVR (n=50) groups, following the exclusion of 101 patients for various reasons. Significant findings included lower baseline HBV DNA in MVR (<20 IU/mL) compared to LLV (67.8 IU/mL, P<0.001) and different AST/ALT ratios (LLV: 1.1, MVR: 1.36, P=0.011). LF was assessed using CHI3L1, FIB-4, and APRI, with LLV showing a higher baseline CHI3L1 (LLV:83.3 ng/mL vs MVR: 54.5 ng/mL, P=0.016) and scores compared to MVR, indicative of fibrosis. CHI3L1 levels in LLV were higher at baseline and weeks 48, 72, and 96 than MVR, with significance at baseline (P=0.038) and week 48 (P=0.034). Liver stiffness measurement (LSM) showed a time-dependent decline in both groups but no significant intergroup differences. Conclusion Non-invasive monitoring of CHB patients who have received treatment indicates that LLV contributes to the progression of LF, necessitating proactive adjustment of antiviral treatment strategies.
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Affiliation(s)
- Jinxian Xu
- Department of Infectious Diseases, Zhejiang University Medical College Affiliated Jinhua Hospital, Jinhua, People’s Republic of China
| | - Yang Zhang
- Department of Infectious Diseases, Zhejiang University Medical College Affiliated Jinhua Hospital, Jinhua, People’s Republic of China
| | - Lujian Zhu
- Department of Infectious Diseases, Zhejiang University Medical College Affiliated Jinhua Hospital, Jinhua, People’s Republic of China
| | - Shiyue Tang
- Department of Infectious Diseases, Zhejiang University Medical College Affiliated Jinhua Hospital, Jinhua, People’s Republic of China
| | - Hanglu Xu
- Department of Infectious Diseases, Zhejiang University Medical College Affiliated Jinhua Hospital, Jinhua, People’s Republic of China
| | - Dehe Zhang
- Department of Infectious Diseases, Zhejiang University Medical College Affiliated Jinhua Hospital, Jinhua, People’s Republic of China
| | - Haijun Chen
- Department of Infectious Diseases, Zhejiang University Medical College Affiliated Jinhua Hospital, Jinhua, People’s Republic of China
| | - Jing Zhou
- Department of Infectious Diseases, Zhejiang University Medical College Affiliated Jinhua Hospital, Jinhua, People’s Republic of China
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12
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Chen YC, Yang CC, Kuo HT, Sheu MJ, Feng IC, Liu CF, Sun CS, Wang SH, Lin CY, Chen CH, Lin SH. Risk Factors and Nomogram Model for Hepatocellular Carcinoma Development in Chronic Hepatitis B Patients with Low-Level Viremia. Int J Med Sci 2024; 21:1661-1671. [PMID: 39006848 PMCID: PMC11241087 DOI: 10.7150/ijms.95861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2024] [Accepted: 06/04/2024] [Indexed: 07/16/2024] Open
Abstract
Background and aim: Patients with chronic hepatitis B patients (CHB) with low-level viremia (LLV) are not necessarily at low risk of developing hepatocellular carcinoma (HCC). The question of whether CHB patients with LLV require immediate antiviral agent (AVT) or long-term AVT remains controversial. The study aims to investigate the risk of HCC development and the risk factors in CHB patients with LLV and construct a nomogram model predicting the risk of HCC. Methods: We conducted a retrospective cohort study that enrolled 16,895 CHB patients from January 2008 to December 2020. The patients were divided into three groups for comparison: the LLV group, maintained virological response (MVR) group and HBV-DNA>2000 group. The cumulative incidence of progression to HCC was assessed. Cox regression analysis was performed to determine the final risk factors, and a nomogram model was constructed. The 10-fold Cross-Validation method was utilized for internal validation. Results: A total of 408 new cases of HCC occurred during the average follow-up period of 5.78 years. The 3, 5, and 10-year cumulative HCC risks in the LLV group were 3.56%, 4.96%, and 9.51%, respectively. There was a significant difference in the cumulative risk of HCC between the HBV-DNA level > 2000 IU/mL and LLV groups (p = 0.049). Independent risk factors for HCC development in LLV group included male gender, age, presence of cirrhosis, and platelets count. The Area Under the Curve (AUC) values for the 3-year and 5-year prediction from our HCC risk prediction model were 0.75 and 0.76, respectively. Conclusion: Patients with LLV and MVR are still at risk for developing HCC. The nomogram established for CHB patient with LLV, incorporating identified significant risk factors, serves as an effective tool for predicting HCC-free outcomes. This nomogram model provides valuable information for determining appropriate surveillance strategies and prescribing AVT.
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Affiliation(s)
- Yu-Ching Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Yongkang District, Tainan, Taiwan
- Department of Internal Medicine, Chi Mei Medical Center, Yongkang District, Tainan, Taiwan
| | - Chun-Chi Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Yongkang District, Tainan, Taiwan
| | - Hsing-Tao Kuo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Yongkang District, Tainan, Taiwan
| | - Ming-Jen Sheu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Yongkang District, Tainan, Taiwan
| | - I-Che Feng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Yongkang District, Tainan, Taiwan
| | - Chung-Feng Liu
- Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan
| | - Chi-Shu Sun
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Yongkang District, Tainan, Taiwan
| | - Su-Hung Wang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Yongkang District, Tainan, Taiwan
| | - Cheng-Yi Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Yongkang District, Tainan, Taiwan
| | - Chi-Hsing Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Yongkang District, Tainan, Taiwan
| | - Sheng-Hsiang Lin
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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13
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Tang Q, Hu P. The antiviral treatment should be initiated before the development of cirrhosis. Hepatobiliary Surg Nutr 2024; 13:136-138. [PMID: 38322213 PMCID: PMC10839712 DOI: 10.21037/hbsn-23-580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Accepted: 12/06/2023] [Indexed: 02/08/2024]
Affiliation(s)
- Qiao Tang
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Peng Hu
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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14
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You H, Wang F, Li T, Xu X, Sun Y, Nan Y, Wang G, Hou J, Duan Z, Wei L, Jia J, Zhuang H. Guidelines for the Prevention and Treatment of Chronic Hepatitis B (version 2022). J Clin Transl Hepatol 2023; 11:1425-1442. [PMID: 37719965 PMCID: PMC10500285 DOI: 10.14218/jcth.2023.00320] [Citation(s) in RCA: 64] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 08/02/2023] [Accepted: 08/03/2023] [Indexed: 09/19/2023] Open
Abstract
To facilitate the achieving of the goal of "eliminating viral hepatitis as a major public health threat by 2030" set by the World Health Organization, the Chinese Society of Hepatology together with the Chinese Society of Infectious Diseases (both are branches of the Chinese Medical Association) organized a panel of experts and updated the guidelines for prevention and treatment of chronic hepatitis B in China (version 2022). With the support of available evidence, this revision of the guidelines focuses on active prevention, large scale testing, and expansion of therapeutic indication of chronic hepatitis B with the aim of reducing the hepatitis B related disease burden.
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Affiliation(s)
- Hong You
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Fusheng Wang
- The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Taisheng Li
- Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Xiaoyuan Xu
- Peking University First Hospital, Beijing, China
| | - Yameng Sun
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yuemin Nan
- Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | | | - Jinlin Hou
- Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Zhongping Duan
- Beijing You-An Hospital, Capital Medical University, Beijing, China
| | - Lai Wei
- Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Jidong Jia
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Hui Zhuang
- Peking University Health Science Center, Beijing, China
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15
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Qiu S, Jin L, Yang D, Zhang D. Clinical application value of hepatitis B virus basal core promoter 1762/1764 and GGTII and GGT in patients with HBV-DNA-positive primary liver cancer. Medicine (Baltimore) 2023; 102:e35699. [PMID: 37904480 PMCID: PMC10615473 DOI: 10.1097/md.0000000000035699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Accepted: 09/27/2023] [Indexed: 11/01/2023] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) is closely related to the occurrence and development of primary liver cancer (PLC). The early diagnosis of PLC is difficult. The study explored the clinical application value of the HBV gene basal core promoter (BCP) region 1762/1764 combined with gamma-glutamyl transpeptidase (GGT) and its isozyme II (GGTII) in PLC. METHODS From June 2017 to June 2021, 145 hepatitis B surface antigen-positive and HBV DNA-positive patients were enrolled in the Third People Hospital of Zigong. Of them, 67 were chronic hepatitis B (CHB) patients, 30 were liver cirrhosis patients, and 48 were patients with hepatitis B-associated PLC. The HBV BCP 1762/1764 mutation was detected through the amplification refractory mutation system fluorescence PCR method, and GGTII was detected using the double-antibody sandwich method. RESULTS The results showed that the serum GGT activity, GGTII level, aspartate aminotransferase (AST) activity, AST/alanine aminotransferase (ALT) ratio, GGT/ALT ratio, and GGT/AST ratio were significantly different between the PLC and CHB groups. Statistically significant differences in serum GGT activity, AST activity, and GGT/ALT ratio were observed between the PLC and LC groups. The BCP 1762/1764 mutation rate between the PLC and CHB groups was statistically significant. The GGTII level in the early PLC (stage I + II) group and the advanced PLC (stage III + IV) group was higher than that in the N-PLC group. Serum GGT activity in the early PLC and advanced PLC groups was higher than that in the N-PLC group. The area under the curve of the receiver operator characteristic curve of GGT and GGTII for diagnosing PLC was 0.775 (95% confidence interval [CI] [0.697, 0.854]) and 0.608 (95% CI [0.512, 0.704]), respectively. The area under curve of GGT and GGTII for diagnosing early PLC was 0.732 (95% CI [0.620, 0.845]) and 0.579 (95% CI [0.452, 0.706]), respectively. CONCLUSION HBV gene BCP 1762/1764 mutation, GGT, and GGTII may be related to PLC occurrence. The HBV gene BCP region 1762/1764 combined with GGT has certain clinical diagnostic values for PLC and early PLC. However, GGTII is not a good indicator of early PLC and is more relevant to advanced PLC.
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Affiliation(s)
- Shunhua Qiu
- Department of Clinical Laboratory, Zigong Third People’s Hospital, Sichuan, P.R.[aff_start] [/aff_end]China
| | - Lifen Jin
- Department of pharmaceutical preparation, Zigong Third People’s Hospital, Sichuan, P.R.[aff_start] [/aff_end]China
| | - Dan Yang
- Department of Clinical Laboratory, Zigong Third People’s Hospital, Sichuan, P.R.[aff_start] [/aff_end]China
| | - Dewen Zhang
- Department of Clinical Laboratory, Zigong Third People’s Hospital, Sichuan, P.R.[aff_start] [/aff_end]China
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16
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Fan P, Li LQ, Chen EQ. The urgency to expand the antiviral indications of general chronic hepatitis B patients. Front Med (Lausanne) 2023; 10:1165891. [PMID: 37275355 PMCID: PMC10235492 DOI: 10.3389/fmed.2023.1165891] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Accepted: 05/02/2023] [Indexed: 06/07/2023] Open
Abstract
In recent years, liver experts have conducted in-depth discussions on whether it is necessary to expand the indication of antiviral therapy for patients with chronic hepatitis B (CHB). Currently, the guidelines are too strict in treating CHB patients. With the deepening understanding of the natural history of hepatitis B virus infection, there is more and more evidence challenging the view that there is no disease progression and no treatment in the immune tolerance period and inactive period. As the price of antiviral agents for CHB has decreased significantly, the availability of antiviral agents for CHB has been considerably improved. Therefore, expanding the indications for antiviral treatment of CHB is of great significance in achieving the goal of eliminating the public health threat of viral hepatitis by 2030, as the World Health Organization has proposed.
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Affiliation(s)
- Ping Fan
- Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, China
| | - Lan-Qing Li
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - En-Qiang Chen
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
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17
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Zhu M, Wang H, Lou T, Xiong P, Zhang J, Li L, Sun Y, Wu Y. Current treatment of chronic hepatitis B: Clinical aspects and future directions. Front Microbiol 2022; 13:975584. [PMID: 36160238 PMCID: PMC9493448 DOI: 10.3389/fmicb.2022.975584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Accepted: 07/26/2022] [Indexed: 11/23/2022] Open
Abstract
Hepatitis B virus (HBV) infection is a public health threat worldwide, and there is no direct treatment yet available. In the event of infection, patients may present liver cirrhosis and cancer, which threaten the patients’ health globally, especially in the Asia-Pacific region and China. In 2019, Chinese hepatopathologists updated the 2015 Guidelines for the Prevention and Treatment of Chronic Hepatitis B as the clinical reference. The other versions formulated by the American Association for the Study of Liver Diseases (2018 AASLD guidelines) (AASLD, 2018), European Association for the Study of the Liver (2017 EASL guidelines) (EASL, 2017), and Asian-Pacific Association for the Study of the Liver (2015 APASL guidelines) (APASL, 2015) also provide clinical guidance. However, there are still some issues that need to be addressed. In the present study, the following aspects will be introduced successively: (1) Who should be treated in the general population according to the guidelines; (2) Treatment of specific populations infected with HBV; (3) Controversial issues in clinical practice; (4) Perspective.
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Affiliation(s)
- Minmin Zhu
- The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Jinhua, China
| | - Hui Wang
- The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Jinhua, China
| | - Tao Lou
- The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Jinhua, China
| | - Pian Xiong
- The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Jinhua, China
| | - Jiebing Zhang
- The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Jinhua, China
| | - Lele Li
- The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Jinhua, China
| | - Yuchao Sun
- The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Jinhua, China
- International Institutes of Medicine, Zhejiang University, Jinhua, China
| | - Yingping Wu
- The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Jinhua, China
- International Institutes of Medicine, Zhejiang University, Jinhua, China
- *Correspondence: Yingping Wu,
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18
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Zhang Q, Cai DC, Hu P, Ren H. Low-level viremia in nucleoside analog-treated chronic hepatitis B patients. Chin Med J (Engl) 2021; 134:2810-2817. [PMID: 34759219 PMCID: PMC8668013 DOI: 10.1097/cm9.0000000000001793] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Indexed: 12/14/2022] Open
Abstract
ABSTRACT Low-level viremia (LLV) was defined as persistent or intermittent episodes of detectable hepatitis B virus (HBV) DNA (<2000 IU/mL, detection limit of 10 IU/mL) after 48 weeks of antiviral treatment. Effective antiviral therapies for chronic hepatitis B (CHB) patients, such as entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF), have been shown to inhibit the replication of HBV DNA and prevent liver-related complications. However, even with long-term antiviral therapy, there are still a number of patients with persistent or intermittent LLV. At present, the research on LLV to address whether adversely affect the clinical outcome is limited, and the follow-up treatment for these patients is open to question. At the same time, the mechanism of LLV is not clear. In this review, we summarize the incidence of LLV, the association between LLV and long-term outcomes, possible mechanisms, and management strategies in these patient populations.
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Affiliation(s)
- Qian Zhang
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
- Department of Infectious Diseases, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550001, China
| | - Da-Chuan Cai
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Peng Hu
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Hong Ren
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
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