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Hu Q, Qi X, Yu Y, Gao Y, Zhang X, Wang Q, Zhang X, Zhuo Y, Li J, Zhang J, Chen L, Huang Y. The efficacy and safety of adding on or switching to peginterferon α-2b in HBeAg-positive chronic hepatitis B patients with long-term entecavir treatment: a multicentre randomised controlled trial. Aliment Pharmacol Ther 2022; 56:1394-1407. [PMID: 36128636 DOI: 10.1111/apt.17222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Revised: 06/27/2022] [Accepted: 09/04/2022] [Indexed: 01/30/2023]
Abstract
BACKGROUND & AIMS The strategies of adding on or switching to peginterferon (PEG-IFN) improved the serological response rates in patients with chronic hepatitis B (CHB) who had previously experienced treatment with nucleos(t)ide analogues. However, robust data on which combination strategy is more effective remain lacking. METHODS In this multicentre, parallel, open-label, randomised, controlled trial, patients with HBeAg-positive CHB who were treated with entecavir ≥2 years, and had hepatitis B surface antigen (HBsAg) <3000 IU/ml, HBeAg <200S/CO and HBV DNA <50 IU/ml were randomly assigned in a 1:1:1 ratio to add on PEG-IFN, switch to PEG-IFN or continue entecavir monotherapy for 48 weeks. The primary endpoint was HBeAg seroconversion at week 48. RESULTS A total of 153 patients were randomised into three treatment arms (50 in add-on, 52 in switch-to and 51 in monotherapy). Compared with continuous entecavir monotherapy, both add-on and switch-to strategies achieved higher rates of HBeAg seroconversion (18.0% vs. 2.0%, p = 0.007; 19.2% vs. 2.0%, p = 0.005, respectively), HBeAg loss (24.0% vs. 5.9%, p = 0.010; 23.1% vs. 5.9%, p = 0.013, respectively), HBsAg < 100 IU/ml (30.0% vs. 0%, p < 0.001; 34.6% vs. 0%, p < 0.001, respectively), and higher HBsAg reduction (-0.90 vs. -0.06 log10 IU/ml, p < 0.001; -0.92 vs. -0.06 log10 IU/ml, p < 0.001, respectively) at week 48. The efficacy was comparable between add-on and switch-to arms (p > 0.05). Adverse events were mainly related to PEG-IFN but generally tolerable. CONCLUSION In patients with CHB who achieved virological response with long-term entecavir, both adding on and switching to PEG-IFN are alternative strategies resulting in higher rates of HBeAg seroconversion and HBsAg reduction than continuous entecavir. CLINICAL TRIALS REGISTRATION Chinese Clinical Trial Registry (www.chictr.org.cn, identifier: ChiCTR-IPR-17012055).
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Affiliation(s)
- Qiankun Hu
- Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Xun Qi
- Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Yiqi Yu
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Yueqiu Gao
- Department of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xinxin Zhang
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qianqian Wang
- Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Xueyun Zhang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Yunhui Zhuo
- Department of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jing Li
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiming Zhang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Liang Chen
- Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Yuxian Huang
- Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.,Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
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Choi HS, Tonthat A, Janssen HL, Terrault NA. Aiming for Functional Cure With Established and Novel Therapies for Chronic Hepatitis B. Hepatol Commun 2022; 6:935-949. [PMID: 34894108 PMCID: PMC9035586 DOI: 10.1002/hep4.1875] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 11/11/2021] [Accepted: 11/18/2021] [Indexed: 12/22/2022] Open
Abstract
Chronic hepatitis B virus (HBV) infection remains difficult to cure due to the persistent, self-replenishing nature of the viral genome and impaired host immune responses. Current treatment goals for chronic hepatitis B (CHB) are to prevent or significantly delay liver-related adverse outcomes and death, and two types of treatments are available: nucleos(t)ide analogues (NAs) and interferons (IFNs). NAs effectively suppress HBV replication, and IFNs improve serological response rates, thereby decreasing the risk of adverse outcomes. However, their efficacy in attaining serological responses, especially functional cure (i.e., loss of serum hepatitis B surface antigen), is very limited. Various strategies such as stopping antiviral therapy or combining therapies have been investigated to enhance response, but efficacy is only modestly improved. Importantly, the development of novel direct-acting antivirals and immunomodulators is underway to improve treatment efficacy and enhance rates of functional cure. The present review provides an overview of the treatment goals and indications, the possibility of expanding indications, and the safety and efficacy of different treatment strategies involving established and/or novel therapies as we continue our search for a cure.
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Affiliation(s)
- Hannah S.J. Choi
- Toronto Center for Liver DiseaseToronto General HospitalTorontoONCanada
| | - Alexander Tonthat
- Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCAUSA
| | | | - Norah A. Terrault
- Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCAUSA
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Colombatto P, Coco B, Bonino F, Brunetto MR. Management and Treatment of Patients with Chronic Hepatitis B: Towards Personalized Medicine. Viruses 2022; 14:701. [PMID: 35458431 PMCID: PMC9027850 DOI: 10.3390/v14040701] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Revised: 03/22/2022] [Accepted: 03/23/2022] [Indexed: 02/07/2023] Open
Abstract
The currently available antiviral treatments (Peg-Interferon-α and Nucleos(t)ide Analogues, NA) for chronic hepatitis B (CHB) achieve a functional cure (serum HBsAg and HDV-DNA clearance) of HBV infection in a limited number of patients. Nevertheless, the continuous pharmacological suppression of viral replication by NA halts liver disease progression lowering the risk of HCC development and improving the survival. In the near future, to fully exploit the potential of old and new drugs for HBV treatment a personalized approach to the patients will be required according to an accurate definition of their virologic, immunologic and clinical profile.
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Affiliation(s)
- Piero Colombatto
- Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Reference Center of the Tuscany Region for Chronic Liver Disease and Cancer, Department of Medical Specialties, University Hospital of Pisa, Via Paradisa 2, 56124 Pisa, Italy; (P.C.); (B.C.)
| | - Barbara Coco
- Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Reference Center of the Tuscany Region for Chronic Liver Disease and Cancer, Department of Medical Specialties, University Hospital of Pisa, Via Paradisa 2, 56124 Pisa, Italy; (P.C.); (B.C.)
| | - Ferruccio Bonino
- Institute of Biostructure and Bioimaging, National Research Council, Via De Amicis 95, 80145 Naples, Italy;
| | - Maurizia R. Brunetto
- Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Reference Center of the Tuscany Region for Chronic Liver Disease and Cancer, Department of Medical Specialties, University Hospital of Pisa, Via Paradisa 2, 56124 Pisa, Italy; (P.C.); (B.C.)
- Institute of Biostructure and Bioimaging, National Research Council, Via De Amicis 95, 80145 Naples, Italy;
- Internal Medicine, Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56127 Pisa, Italy
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Hirode G, Choi HSJ, Chen CH, Su TH, Seto WK, Van Hees S, Papatheodoridi M, Lens S, Wong G, Brakenhoff SM, Chien RN, Feld J, Sonneveld MJ, Chan HLY, Forns X, Papatheodoridis GV, Vanwolleghem T, Yuen MF, Hsu YC, Kao JH, Cornberg M, Hansen BE, Jeng WJ, Janssen HLA. Off-Therapy Response After Nucleos(t)ide Analogue Withdrawal in Patients With Chronic Hepatitis B: An International, Multicenter, Multiethnic Cohort (RETRACT-B Study). Gastroenterology 2022; 162:757-771.e4. [PMID: 34762906 DOI: 10.1053/j.gastro.2021.11.002] [Citation(s) in RCA: 120] [Impact Index Per Article: 40.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 10/28/2021] [Accepted: 11/01/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS Functional cure, defined based on hepatitis B surface antigen (HBsAg) loss, is rare during nucleos(t)ide analogue (NA) therapy and guidelines on finite NA therapy have not been well established. We aim to analyze off-therapy outcomes after NA cessation in a large, international, multicenter, multiethnic cohort of patients with chronic hepatitis B (CHB). METHODS This cohort study included patients with virally suppressed CHB who were hepatitis B e antigen (HBeAg)-negative and stopped NA therapy. Primary outcome was HBsAg loss after NA cessation, and secondary outcomes included virologic, biochemical, and clinical relapse, alanine aminotransferase flare, retreatment, and liver-related events after NA cessation. RESULTS Among 1552 patients with CHB, cumulative probability of HBsAg loss was 3.2% at 12 months and 13.0% at 48 months of follow-up. HBsAg loss was higher among Whites (vs Asians: subdistribution hazard ratio, 6.8; 95% confidence interval, 2.7-16.8; P < .001) and among patients with HBsAg levels <100 IU/mL at end of therapy (vs ≥100 IU/mL: subdistribution hazard ratio, 22.5; 95% confidence interval, 13.1-38.7; P < .001). At 48 months of follow-up, Whites with HBsAg levels <1000 IU/mL and Asians with HBsAg levels <100 IU/mL at end of therapy had a high predicted probability of HBsAg loss (>30%). Incidence rate of hepatic decompensation and hepatocellular carcinoma was 0.48 per 1000 person-years and 0.29 per 1000 person-years, respectively. Death occurred in 7/19 decompensated patients and 2/14 patients with hepatocellular carcinoma. CONCLUSIONS The best candidates for NA withdrawal are virally suppressed, HBeAg- negative, noncirrhotic patients with CHB with low HBsAg levels, particularly Whites with <1000 IU/mL and Asians with <100 IU/mL. However, strict surveillance is recommended to prevent deterioration.
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Affiliation(s)
- Grishma Hirode
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada; The Toronto Viral Hepatitis Care Network, Toronto, Canada
| | - Hannah S J Choi
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada
| | | | - Tung-Hung Su
- National Taiwan University Hospital, Taipei, Taiwan
| | - Wai-Kay Seto
- Department of Medicine and State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, Special administrative regions of China
| | - Stijn Van Hees
- Department of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium
| | | | - Sabela Lens
- Hospital Clinic Barcelona, IDIBAPS and CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Grace Wong
- The Chinese University of Hong Kong, Hong Kong, Special administrative regions of China
| | - Sylvia M Brakenhoff
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
| | - Rong-Nan Chien
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital Linkou Medical Center, Chang Gung University, Linkou, Taiwan
| | - Jordan Feld
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada; The Toronto Viral Hepatitis Care Network, Toronto, Canada
| | - Milan J Sonneveld
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
| | - Henry L Y Chan
- The Chinese University of Hong Kong, Hong Kong, Special administrative regions of China
| | - Xavier Forns
- Hospital Clinic Barcelona, IDIBAPS and CIBEREHD, University of Barcelona, Barcelona, Spain
| | | | - Thomas Vanwolleghem
- Department of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium
| | - Man-Fung Yuen
- Department of Medicine and State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, Special administrative regions of China
| | - Yao-Chun Hsu
- E-Da Hospital/I-Shou University, Kaohsiung, Taiwan
| | | | - Markus Cornberg
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany Centre for Individualized Infection Medicine, Hannover, Germany
| | - Bettina E Hansen
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada; The Toronto Viral Hepatitis Care Network, Toronto, Canada
| | - Wen-Juei Jeng
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital Linkou Medical Center, Chang Gung University, Linkou, Taiwan
| | - Harry L A Janssen
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada; The Toronto Viral Hepatitis Care Network, Toronto, Canada.
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Leowattana W, Leowattana T. Chronic hepatitis B: New potential therapeutic drugs target. World J Virol 2022; 11:57-72. [PMID: 35117971 PMCID: PMC8788212 DOI: 10.5501/wjv.v11.i1.57] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 08/13/2021] [Accepted: 01/05/2022] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis B (CHB) infection remains the most causative agent of liver-related morbidity and mortality worldwide. It impacts nearly 300 million people. The current treatment for chronic infection with the hepatitis B virus (HBV) is complex and lacks a durable treatment response, especially hepatitis B surface antigen (HBsAg) loss, necessitating indefinite treatment in most CHB patients due to the persistence of HBV covalently closed circular DNA (cccDNA). New drugs that target distinct steps of the HBV life cycle have been investigated, which comprise inhibiting the entry of HBV into hepatocytes, disrupting or silencing HBV cccDNA, modulating nucleocapsid assembly, interfering HBV transcription, and inhibiting HBsAg release. The achievement of a functional cure or sustained HBsAg loss in CHB patients represents the following approach towards HBV eradication. This review will explore the up-to-date advances in the development of new direct-acting anti-HBV drugs. Hopefully, with the combination of the current antiviral drugs and the newly developed direct-acting antiviral drugs targeting the different steps of the HBV life cycle, the ultimate eradication of CHB infection will soon be achieved.
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Affiliation(s)
- Wattana Leowattana
- Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
| | - Tawithep Leowattana
- Department of Medicine, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand
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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.
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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.
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Ohsaki E, Suwanmanee Y, Ueda K. Chronic Hepatitis B Treatment Strategies Using Polymerase Inhibitor-Based Combination Therapy. Viruses 2021; 13:v13091691. [PMID: 34578273 PMCID: PMC8473100 DOI: 10.3390/v13091691] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 08/19/2021] [Accepted: 08/25/2021] [Indexed: 12/12/2022] Open
Abstract
Viral polymerase is an essential enzyme for the amplification of the viral genome and is one of the major targets of antiviral therapies. However, a serious concern to be solved in hepatitis B virus (HBV) infection is the difficulty of eliminating covalently closed circular (ccc) DNA. More recently, therapeutic strategies targeting various stages of the HBV lifecycle have been attempted. Although cccDNA-targeted therapies are attractive, there are still many problems to be overcome, and the development of novel polymerase inhibitors remains an important issue. Interferons and nucleos(t)ide reverse transcriptase inhibitors (NRTIs) are the only therapeutic options currently available for HBV infection. Many studies have reported that the combination of interferons and NRTI causes the loss of hepatitis B surface antigen (HBsAg), which is suggestive of seroconversion. Although NRTIs do not directly target cccDNA, they can strongly reduce the serum viral DNA load and could suppress the recycling step of cccDNA formation, improve liver fibrosis/cirrhosis, and reduce the risk of hepatocellular carcinoma. Here, we review recent studies on combination therapies using polymerase inhibitors and discuss the future directions of therapeutic strategies for HBV infection.
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Yeh ML, Huang JF, Yu ML, Chuang WL. Hepatitis b infection: progress in identifying patients most likely to respond to peginterferon alfa. Expert Rev Gastroenterol Hepatol 2021; 15:427-435. [PMID: 33338385 DOI: 10.1080/17474124.2021.1866985] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Accepted: 12/17/2020] [Indexed: 02/07/2023]
Abstract
Introduction: Despite the disadvantage of side effects, pegylated interferon alpha (Peg-IFN α) remains an indispensable agent for chronic hepatitis B (CHB) due to its immunomodulatory effect. The selection of a patient most likely to have a favorable response becomes an essential issue for Peg-IFN α therapy.Areas covered: Recent progress in the prediction of the treatment response to Peg-IFN α.Expert opinion: Before Peg-IFN α therapy, baseline host and viral factors, including female sex, younger age, a high alanine aminotransferase level, HBV genotype A or B, and low viral load, predict a favorable response. In addition, on-treatment viral kinetics of hepatitis B surface antigen (HBsAg), e antigen (HBeAg) and HBV DNA help clinicians determine whether to continue or discontinue Peg-IFN α therapy. The novel HBV markers hepatitis B core-related antigen and HBV RNA have recently been investigated as useful predictors. The limited efficacy of Peg-IFN α monotherapy facilitated the development of new strategies of 'add-on' or 'switch to' Peg-IFN α in patients receiving long-term nucleot(s)ide analog treatment, which may lead to an increase in HBeAg and HBsAg loss. In summary, tailored Peg-IFN α therapeutic strategies based on predictors extended the landscape for CHB treatment.
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Affiliation(s)
- Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine, Lipid Science and Aging Research Center, and Hepatitis Research Center, College of Medicine, and Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine, Lipid Science and Aging Research Center, and Hepatitis Research Center, College of Medicine, and Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine, Lipid Science and Aging Research Center, and Hepatitis Research Center, College of Medicine, and Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine, Lipid Science and Aging Research Center, and Hepatitis Research Center, College of Medicine, and Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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Younossi ZM, Stepanova M, Younossi I, Racila A. Development and validation of a hepatitis B-specific health-related quality-of-life instrument: CLDQ-HBV. J Viral Hepat 2021; 28:484-492. [PMID: 33306234 DOI: 10.1111/jvh.13451] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Revised: 11/20/2020] [Accepted: 11/26/2020] [Indexed: 01/08/2023]
Abstract
Hepatitis B virus (HBV) carries a large global burden. Efforts abound to decrease the burden, which necessitates reporting of patient-reported outcomes (PROs). We aimed to develop and validate an HBV-specific PRO instrument using the Chronic Liver Disease Questionnaire (CLDQ). Data were obtained from patients enrolled in our HBV registries who completed the CLDQ, Short Form-36 (SF-36) and FACIT-F. The sample was split randomly 1:1 into training and testing groups. A standard PRO instrument validation pipeline was used to develop and validate the new CLDQ-HBV instrument. HBV patients (n = 1,339) were 48 ± 13 years old, 60% male, 8% cirrhosis, with 53% receiving oral antivirals (OAV). After reduction of 10 redundant items, exploratory factor analysis for the remaining 19 items found 95% of variance was explained by five factors-emotional function, fatigue, systemic symptoms, worry and sleep. Good-to-excellent internal consistency was found: Cronbach's alphas 0.70-0.90 and item-to-own-domain correlations >0.50 for 18/19 items. Known-group validity tests discriminated between HBV patients with and without cirrhosis, with FIB-4 ≥ 3.25 vs <3.25, with and without history of depression or clinically overt fatigue (all p < 0.0001), and treatment (all p < 0.05, all but one <0.0001). After 48-week follow-up, HBV patients receiving OAV (N = 144) with ≥2.7 log 10/mL decline in HBV viral load experienced significant improvements in fatigue, worry and total CLDQ-HBV scores (p < 0.05). The newly developed CLDQ-HBV is a short, disease-specific PRO instrument for HBV patients which was developed and validated using large data set and an established methodology showing excellent psychometric characteristics.
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Affiliation(s)
- Zobair M Younossi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
| | - Maria Stepanova
- Center for Outcomes Research in Liver Disease, Washington, DC, USA
| | - Issah Younossi
- Center for Outcomes Research in Liver Disease, Washington, DC, USA
| | - Andrei Racila
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
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10
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Yoshida K, Enomoto M, Tamori A, Nishiguchi S, Kawada N. Combination of Entecavir or Tenofovir with Pegylated Interferon-α for Long-Term Reduction in Hepatitis B Surface Antigen Levels: Simultaneous, Sequential, or Add-on Combination Therapy. Int J Mol Sci 2021; 22:1456. [PMID: 33535672 PMCID: PMC7867160 DOI: 10.3390/ijms22031456] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 01/21/2021] [Accepted: 01/27/2021] [Indexed: 12/16/2022] Open
Abstract
Seroclearance of hepatitis B surface antigen (HBsAg) ("functional cure") is the optimal endpoint of antiviral therapy for chronic hepatitis B virus (HBV) infection. Currently available anti-HBV therapy includes nucleoside/nucleotide analogs (NAs) and peginterferon-α (Peg-IFNα). Combination of NAs and Peg-IFNα, each with different mechanisms of action, is an attractive approach for treating chronic HBV infection. In earlier studies, compared with monotherapy using IFNα, combination therapy showed greater on-treatment HBV DNA suppression but no difference in the sustained response. However, responses to the combination of non-pegylated IFNα with lamivudine or adefovir were not assessed based on HBsAg quantification but were defined by normal alanine aminotransferase levels, testing negative for hepatitis B e-antigen, and low HBV DNA load over a short term. Here, we reviewed previous reports regarding the effects of combination therapy of entecavir or tenofovir with Peg-IFNα, focusing on long-term reduction in HBsAg levels. Regimens of combination therapy were classified into "simultaneous" combination ("de novo" strategy); "sequential" combination, which involved starting with one therapy followed by the other ("switch-to" strategy); "add-on" combination, which involved adding Peg-IFNα to an ongoing NAs. Some studies have shown promising results, but there is no robust evidence that combination therapy is superior to monotherapy. Large studies are needed to assess the safety and efficacy of combination therapies to increase the rates of HBsAg seroclearance over the long term.
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Affiliation(s)
- Kanako Yoshida
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan; (K.Y.); (A.T.); (N.K.)
| | - Masaru Enomoto
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan; (K.Y.); (A.T.); (N.K.)
| | - Akihiro Tamori
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan; (K.Y.); (A.T.); (N.K.)
| | - Shuhei Nishiguchi
- Division of Medical Science of Regional Cooperation for Liver Diseases, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan;
- Department of Internal Medicine, Kano General Hospital, Osaka 531-0041, Japan
| | - Norifumi Kawada
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan; (K.Y.); (A.T.); (N.K.)
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Hu C, Song Y, Tang C, Li M, Liu J, Liu J, Liao M, Zhou F, Zhang YY, Zhou Y. Effect of Pegylated Interferon Plus Tenofovir Combination on Higher Hepatitis B Surface Antigen Loss in Treatment-naive Patients With Hepatitis B e Antigen -positive Chronic Hepatitis B: A Real-world Experience. Clin Ther 2021; 43:572-581.e3. [PMID: 33516527 DOI: 10.1016/j.clinthera.2020.12.022] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Revised: 12/25/2020] [Accepted: 12/30/2020] [Indexed: 12/26/2022]
Abstract
PURPOSE The loss of serum hepatitis B surface antigen (HBsAg) in patients with chronic hepatitis B (CHB) is considered an ideal clinical outcome but rarely achieved with current standard of care. We evaluated the effectiveness in inducing HBsAg seroclearance in a real-world clinical cohort of Chinese patients with CHB treated with a combination of pegylated interferon (Peg-IFN) with tenofovir disoproxil fumarate (TDF) or monotherapy with each agent. METHODS A total of 330 patients with CHB were assigned to receive Peg-IFN plus TDF for 48 weeks (Peg-IFN plus TDF group), Peg-IFN alone for 48 weeks (Peg-IFN group), or TDF alone for 144 weeks (TDF group). The primary end point was the percentages of patients who achieved HBsAg seroclearance at week 72. Differences from the baseline characteristics and treatment data were compared using the χ2 test for categorical variables or 1-way ANOVA for continuous variables. A Kaplan-Meier test was performed to compare the HBsAg loss among the 3 groups. Discrimination of responders versus nonresponders was quantified using AUC curves. Optimal cut-offs were selected based on Youden's J statistic defined as J = sensitivity + specificity-1. FINDINGS At week 72, the Kaplan-Meier cumulative HBsAg loss was 11.5% in the Peg-IFN plus TDF group, 5.7% in the Peg-IFN group, and 0% in the TDF group. The percentage of patients with HBsAg loss was comparable in the Peg-IFN plus TDF and Peg-IFN groups (P = 0.143), but both were significantly higher than that in the TDF group (P = 0.000 and P = 0.010). In addition, a significantly higher percentage of patients in the combination group and Peg-IFN group had serum HBsAg of <100 IU/mL compared with the TDF group (32.7% vs 23.6% vs 9.2%; P < 0.001) but no significant differences in the percentages of patients with HBsAg <1000 IU/mL, the undetectable serum HBV DNA and hepatitis B e antigen seroconversion. Our model predicted serum HBsAg loss at week 72 (AUC = 0.846) if the HBsAg level was reduced by > 1.5 log10 IU/mL from baseline at treatment week 24, an optimal timepoint for prediction of HBsAg loss in this cohort. IMPLICATIONS A 48-week course of Peg-IFN and TDF combination therapy led to profound reduction in serum HBsAg level, resulting in a significantly higher rate of HBsAg loss compared with TDF monotherapy. Patients with steep HBsAg decline >1.5 log10 IU/mL at week 24 well signaled a higher probability of achieving HBsAg loss at week 72.
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Affiliation(s)
- Chengguang Hu
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yangda Song
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Cuirong Tang
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Meng Li
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Junwei Liu
- Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jia Liu
- Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Minjun Liao
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Fuyuan Zhou
- Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | | | - Yuanping Zhou
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
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Yang J, Guo R, Yan D, Lu H, Zhang H, Ye P, Jin L, Diao H, Li L. Plasma Level of ADAMTS13 or IL-12 as an Indicator of HBeAg Seroconversion in Chronic Hepatitis B Patients Undergoing m-ETV Treatment. Front Cell Infect Microbiol 2020; 10:335. [PMID: 32793509 PMCID: PMC7393286 DOI: 10.3389/fcimb.2020.00335] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Accepted: 06/03/2020] [Indexed: 02/05/2023] Open
Abstract
The ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin motif repeats 13) is a key factor involved in coagulation process and plays a vital role in the progression and prognosis of chronic hepatitis B (CHB) patients with antiviral treatment. However, there are few reports about the profile of plasma ADAMTS13 in CHB patients during entecavir maleate (m-ETV) treatment. One hundred two HBV e antigen (HBeAg)-positive CHB patients on continuous m-ETV naive for at least 96 weeks were recruited. Patients with liver cirrhosis were excluded using liver biopsies and real-time elastography. Plasma ADAMTS13 and interleukin 12 (IL-12) levels were evaluated at baseline and12, 24, 48, 72, and 96 weeks, respectively. The change of ADAMTS13 (ΔADAMTS13) and IL-12 (ΔIL-12) possesses a significant relationship in CHB patients with HBeAg seroconversion (SC) at 48-week m-ETV treatment (p < 0.001), but no significance in patients without SC. Furthermore, Cox multivariate analysis demonstrated that the change of ADAMTS13 (IL-12) is an independent predictor for HBeAg SC at week 96, and the area under the receiver operating characteristic curve for the ΔADAMTS13 (ΔIL-12) in CHB patients with 48-week m- ETV treatment is 0.8204 (0.8354) (p < 0.001, both) to predict HBeAg SC at week 96. The results suggested that higher increased ADAMTS13 and IL-12 after 48-week m-ETV treatment contributed to an enhanced probability of HBeAg SC, although the mechanism is undetermined. Quantification of ADAMTS13 (IL-12) during m-ETV treatment may help to predict long-term HBeAg SC in CHB patients.
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Affiliation(s)
- Jiezuan Yang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Renyong Guo
- Key Laboratory of Clinical in vitro Diagnostic Techniques of Zhejiang Province, Department of Laboratory Medicine, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Dong Yan
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Haifeng Lu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Hua Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Ping Ye
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Linfeng Jin
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Hongyan Diao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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13
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Li H, Yan L, Shi Y, Lv D, Shang J, Bai L, Tang H. Hepatitis B Virus Infection: Overview. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1179:1-16. [PMID: 31741331 DOI: 10.1007/978-981-13-9151-4_1] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Hepatitis B virus (HBV) is a DNA virus, belonging to the Hepadnaviridae family. It is a partially double-stranded DNA virus with a small viral genome (3.2 kb). Chronic HBV infection remains a global public health problem. If left untreated, chronic HBV infection can progress to end-stage liver disease, such as liver cirrhosis and hepatocellular carcinoma (HCC). In recent years, tremendous advances in the field of HBV basic and clinical research have been achieved, ranging from the HBV biological characteristics, immunopathogenesis, and animal models to the development of new therapeutic strategies and new drugs against HBV. In this overview, we begin with a brief history of HBV discovery and treatment milestones. We then briefly summarize the HBV research advances, which will be detailed in the following chapters.
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Affiliation(s)
- Hong Li
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Libo Yan
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Ying Shi
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Duoduo Lv
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jin Shang
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Lang Bai
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Hong Tang
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
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14
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Tao Y, Wu D, Zhou L, Chen E, Liu C, Tang X, Jiang W, Han N, Li H, Tang H. Present and Future Therapies for Chronic Hepatitis B. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1179:137-186. [PMID: 31741336 DOI: 10.1007/978-981-13-9151-4_6] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Chronic hepatitis B (CHB) remains the leading cause of liver-related morbidity and mortality across the world. If left untreated, approximately one-third of these patients will progress to severe end-stage liver diseases including liver failure, cirrhosis, and hepatocellular carcinoma (HCC). High level of serum HBV DNA is strongly associated with the development of liver failure, cirrhosis, and HCC. Therefore, antiviral therapy is crucial for the clinical management of CHB. Current antiviral drugs including nucleoside/nucleotide analogues (NAs) and interferon-α (IFN-α) can suppress HBV replication and reduce the progression of liver disease, thus improving the long-term outcomes of CHB patients. This chapter will discuss the standard and optimization antiviral therapies in treatment-naïve and treatment-experienced patients, as well as in the special populations. The up-to-date advances in the development of new anti-HBV agents will be also discussed. With the combination of the current antiviral drugs and the newly developed antiviral agents targeting the different steps of the viral life cycle or the newly developed agents modulating the host immune responses, the ultimate eradication of HBV will be achieved in the future.
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Affiliation(s)
- Yachao Tao
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Dongbo Wu
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Lingyun Zhou
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Enqiang Chen
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Changhai Liu
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xiaoqiong Tang
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Wei Jiang
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Ning Han
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Hong Li
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
| | - Hong Tang
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
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15
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Li G, Zhang Q, Yu Y, Qiu C, Zhang H, Zhang M, Song Z, Yang Y, Hong J, Lu J, Li N, Tang Q, Xu L, Wang X, Zhang W, Chen Z. Histological responses of peginterferon alpha add-on therapy in patients with chronic hepatitis B with advanced liver fibrosis after long-term nucleos(t)ide analog treatment. J Viral Hepat 2019; 26 Suppl 1:50-58. [PMID: 31380590 DOI: 10.1111/jvh.13152] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2019] [Accepted: 05/15/2019] [Indexed: 01/05/2023]
Abstract
Although long-term antiviral treatment with nucleos(t)ide analogs (NAs) can lead to histological improvement in patients with chronic hepatitis B (CHB), a substantial proportion of patients still fail to achieve regression of fibrosis. Here, we investigated whether peginterferon alpha (Peg-IFNα） add-on therapy had benefits on fibrosis regression in patients with sustained severe fibrosis even after long-term NA treatment. We conducted a retrospective analysis of data from 50 patients with CHB receiving 48 weeks of Peg-IFNα add-on therapy. All enrolled patients had advanced fibrosis or cirrhosis (S score ≥ 3) at baseline and underwent NA treatment for at least 1 year before Peg-IFNα addition. Paired liver biopsies before and after Peg-IFNα add-on treatment and laboratory tests at baseline, 24 weeks of treatment, 48 weeks of treatment and long-term follow-up were analysed. Of the 50 patients enrolled in this study, 34 patients (68.0%) had significant regression of fibrosis, and 42 (84.0%) showed significant remission of inflammation after Peg-IFNα add-on treatment. Compared with nonresponders, patients with significant histological improvement showed faster hepatitis B surface antigen (HBsAg) decline and tended to have higher cumulative hepatitis B e antigen (HBeAg) and HBsAg loss rates during long-term follow-up. Peg-IFNα add-on therapy led to significant regression of fibrosis and resolution of inflammation in patients with advanced fibrosis after long-term NA treatment.
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Affiliation(s)
- Guojun Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Qiran Zhang
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Yiqi Yu
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Chao Qiu
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.,Institutes of Biomedical Sciences and Key Laboratory of Medical Molecular Virology of Ministry of Education and Health, Fudan University, Shanghai, China
| | - Hanyue Zhang
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Miaoqu Zhang
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Zhangzhang Song
- Department of Hepatology, The Second Hospital of Yinzhou of Ningbo, Ningbo, China
| | - Yusheng Yang
- Department of Hepatology, The Second Hospital of Yinzhou of Ningbo, Ningbo, China
| | - Jiemin Hong
- Department of Infectious Diseases, Shenzhen University General Hospital, Guangdong Sheng, China
| | - Jian Lu
- Department of Infectious Diseases, Shenzhen University General Hospital, Guangdong Sheng, China
| | - Niuniu Li
- Department of Infectious Diseases, Shenzhen University General Hospital, Guangdong Sheng, China
| | - Quanzhen Tang
- Department of Infectious Diseases, Shenzhen University General Hospital, Guangdong Sheng, China
| | - Long Xu
- Department of Infectious Diseases, Shenzhen University General Hospital, Guangdong Sheng, China
| | - Xuanyi Wang
- Institutes of Biomedical Sciences and Key Laboratory of Medical Molecular Virology of Ministry of Education and Health, Fudan University, Shanghai, China
| | - Wenhong Zhang
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.,Institutes of Biomedical Sciences and Key Laboratory of Medical Molecular Virology of Ministry of Education and Health, Fudan University, Shanghai, China
| | - Zhi Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
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16
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Zhang L, Zhang FK. Recent advances in assessment and treatment of chronic hepatitis B. Shijie Huaren Xiaohua Zazhi 2019; 27:209-219. [DOI: 10.11569/wcjd.v27.i4.209] [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] [Indexed: 02/06/2023] Open
Abstract
This paper reviews the recent advances in the assessment and treatment of chronic hepatitis B with regard to predicting inflammation and fibrosis with non-invasive biomarkers and transient elastography, clinical benefits of long-term nucleos(t)ide analog (NA) antiviral therapy, serological benefits (HBeAg and HBsAg loss) of concurrent or sequential NAs and pegylated interferon, as well as risk factors for the development of hepatocellular carcinoma.
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Affiliation(s)
- Li Zhang
- Department of Gastroenterology, Beijing Shijingshan Hospital, Beijing 100043, China
| | - Fu-Kui Zhang
- Department of Gastroenterology, Beijing Shijingshan Hospital, Beijing 100043, China
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