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Tan L, Mo Z, Gan W, Gao Z, Zhu J, Wu Z. The remodeling of B-cell subsets was correlated with the clearance of hepatitis B antigen during pegylated IFN α-2a therapy in CHB patients. Ann Med 2025; 57:2463569. [PMID: 39957563 PMCID: PMC11834791 DOI: 10.1080/07853890.2025.2463569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 04/19/2024] [Accepted: 06/01/2024] [Indexed: 02/18/2025] Open
Abstract
BACKGROUND B-cell may participate in the cellular immune process of hepatitis B antigen clearance. However, the function and specific mechanism of B-cell during interferon-pegylated interferon α-2a (Peg-IFN-α) treatment in chronic hepatitis B (CHB) patients have not yet been described. METHODS A total of 150 CHB patients enrolled in this study, who received 48 weeks of Peg-IFN α treatment. The differentiation clusters CD19, CD24, CD27, CD38, CD40, and CD80 of B cell surface markers in CHB patients were detected by flow cytometry. Spearman correlation and Logistic regression analysis were performed for the analysis. RESULTS The clearance rate of HBsAg increased significantly with the duration of Peg-IFN-α treatment, reaching 32.2% by 48 weeks. During the Peg-IFN-α therapy, the frequency of B-cell and its subsets increased significantly. However, we did not observe any significant difference in the frequency of the B-cell and its subsets in patients with or without HBsAg clearance after 48 weeks Peg-IFN-α treatment. The change in HBsAg value was negatively related to the change in plasmablasts (CD19+CD38+) level before and after 48 weeks treatment (r = -0.326, p = 0.006). Moreover, the results showed that HBsAg <288.70 IU/mL at baseline and HBsAg <58.05 IU/mL at 12 weeks were strong predictors of HBsAg clearance in patients with 48 weeks Peg-IFN-α treatment. CONCLUSION The remodeling of B cell subsets, especially plasmablasts (CD19+CD38+), during Peg-IFN-α treatment was closed associated with the clearance of hepatitis B antigen.
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Affiliation(s)
- Lei Tan
- Department of Medical Ultrasonic, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Zhishuo Mo
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Key Laboratory of Topical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong, China
| | - Weiqiang Gan
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Key Laboratory of Topical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong, China
| | - Zhiliang Gao
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Key Laboratory of Topical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong, China
| | - Jianyun Zhu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Key Laboratory of Topical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong, China
| | - Zeqian Wu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Key Laboratory of Topical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong, China
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Wang T, Tang F, Li F, Chen J, Yan F, Du Q, Yin W, Liang J, Liu L, Wang F, Xu B, Ye Q, Xiang H. Discussion on the duration of response following HBsAg clearance in patients with chronic hepatitis B treated with PegIFNα-2b. Front Immunol 2025; 16:1518048. [PMID: 40264777 PMCID: PMC12011802 DOI: 10.3389/fimmu.2025.1518048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2024] [Accepted: 03/20/2025] [Indexed: 04/24/2025] Open
Abstract
Aim Functional cure strategies based on interferon therapy for chronic hepatitis B (CHB) are gaining increasing attention among clinicians. However, studies investigating the duration of response after achieving HBsAg clearance with interferon treatment are limited. This study aims to explore the patterns of sustained response following HBsAg clearance in patients treated with pegylated interferon alpha-2b (PegIFNα-2b) through long-term follow-up, providing guidance for clinical practice. Methods We collected data from CHB patients who achieved HBsAg clearance and were treated with either PegIFNα-2b monotherapy or in combination with nucleos(t)ide analogs (NAs) at Tianjin Third Central Hospital from January 2018 to May 2024. Regular follow-up assessments were conducted to observe the dynamic changes in HBsAg, HBV DNA, and liver function during the follow-up period. We recorded the time to HBsAg reversion (defined as HBsAg ≥ 0.05 IU/mL), analyzed the patterns of HBsAg reversion, and investigated the optimal time points for evaluating sustained HBsAg clearance. Results A total of 173 patients with CHB or compensated hepatitis B cirrhosis were included. The mean age was 41.5 ± 9.0 years, with 16.19% of patients having compensated cirrhosis. The median follow-up duration was 89.3 weeks (range: 18.6 to 289.1 weeks). HBsAg reversion occurred in 26 patients, yielding a reversion rate of 15.03% (26/173). Among these 26 patients, 50% (13/26) experienced reversion within 24 weeks, and 80.77% within 48 weeks; thereafter, the number of reversions gradually decreased. At 48 weeks post-treatment cessation, the HBsAg sustained response rate was 95.45%, stabilizing at 100% after 120 weeks. Among patients with regular follow-ups, virtually none experienced reversion beyond 72 weeks. At the time of HBsAg reversion, all 26 patients exhibited normal alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) levels, with a median HBsAg level of 0.70 IU/mL (range: 0.05 to 8.13 IU/mL), and only one patient showing low-level positive HBV DNA (117 IU/mL). No adverse events, including liver failure, decompensation, or hepatocellular carcinoma, occurred during the follow-up period. Conclusions Patients with chronic hepatitis B treated with PegIFNα-2b demonstrated favorable long-term persistence of HBsAg clearance. However, there remains a risk of HBsAg reversion after treatment cessation, predominantly within the first 48 weeks. HBsAg sustained response (HSR) at 48 weeks post-treatment is a critical follow-up time point for CHB patients post-HBsAg clearance, with HSR at 72 weeks potentially representing an ideal follow-up timeframe, while HSR at 120 weeks may serve as a marker for extended follow-up.
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Affiliation(s)
- Tao Wang
- Department of Gastroenterology and Hepatology, Tianjin University Central Hospital (Tianjin Third Central Hospital), Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin Institute of Hepatobiliary Disease, Tianjin, China
| | - Fei Tang
- Department of Gastroenterology and Hepatology, Tianjin University Central Hospital (Tianjin Third Central Hospital), Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin Institute of Hepatobiliary Disease, Tianjin, China
| | - Fenghui Li
- Department of Gastroenterology and Hepatology, Tianjin University Central Hospital (Tianjin Third Central Hospital), Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin Institute of Hepatobiliary Disease, Tianjin, China
| | - Jing Chen
- The Third Central Clinical College of Tianjin Medical University, Tianjin University Central Hospital (Tianjin Third Central Hospital), Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin Institute of Hepatobiliary Disease, Tianjin, China
| | - Fei Yan
- The Third Central Clinical College of Tianjin Medical University, Tianjin University Central Hospital (Tianjin Third Central Hospital), Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin Institute of Hepatobiliary Disease, Tianjin, China
| | - Qin Du
- Nankai University Affiliated Third Center Hospital, Tianjin University Central Hospital (Tianjin Third Central Hospital), Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin Institute of Hepatobiliary Disease, Tianjin, China
| | - Weili Yin
- Department of Gastroenterology and Hepatology, Tianjin University Central Hospital (Tianjin Third Central Hospital), Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin Institute of Hepatobiliary Disease, Tianjin, China
| | - Jing Liang
- Department of Gastroenterology and Hepatology, Tianjin University Central Hospital (Tianjin Third Central Hospital), Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin Institute of Hepatobiliary Disease, Tianjin, China
| | - Lei Liu
- Department of Gastroenterology and Hepatology, Tianjin University Central Hospital (Tianjin Third Central Hospital), Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin Institute of Hepatobiliary Disease, Tianjin, China
| | - Fang Wang
- Department of Gastroenterology and Hepatology, Tianjin University Central Hospital (Tianjin Third Central Hospital), Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin Institute of Hepatobiliary Disease, Tianjin, China
| | - Baiguo Xu
- Department of Gastroenterology and Hepatology, Tianjin University Central Hospital (Tianjin Third Central Hospital), Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin Institute of Hepatobiliary Disease, Tianjin, China
| | - Qing Ye
- Department of Gastroenterology and Hepatology, Tianjin University Central Hospital (Tianjin Third Central Hospital), Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin Institute of Hepatobiliary Disease, Tianjin, China
| | - Huiling Xiang
- Department of Gastroenterology and Hepatology, Tianjin University Central Hospital (Tianjin Third Central Hospital), Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin Institute of Hepatobiliary Disease, Tianjin, China
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Liang H, Zheng X, Liu Y, Mao Q, Wu C, Lin L, Huang Z, Chen Y, Zhang M, Zhang L, Min J, Hu M, Luo H, Chen S, Gu X. Effects of Different Antiviral Treatments on Liver Inflammation and Fibrosis in Patients With Chronic Hepatitis B. J Viral Hepat 2025; 32:e70019. [PMID: 40087906 DOI: 10.1111/jvh.70019] [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: 09/19/2024] [Revised: 01/19/2025] [Accepted: 02/14/2025] [Indexed: 03/17/2025]
Abstract
Oral nucleotide analogues (NAs) and peginterferon-α injections are commonly used for the treatment of patients with chronic hepatitis B (CHB). This study aims to evaluate the effects of different antiviral therapies on the degree of liver inflammation and fibrosis in CHB patients. This was a retrospective cohort study. A total of 101 CHB patients were admitted to the Liver Center of Xiamen Hospital of Traditional Chinese Medicine from 2017 to 2021 and were divided into three groups for different antiviral treatments: NAs therapy group (n = 36), peginterferon-α therapy group (n = 38) and nonantiviral therapy group (n = 27). The differences in degrees of liver inflammation and liver fibrosis between two histopathologic biopsies before and after treatment were analysed and compared to evaluate the efficacy of different treatments. The degrees of liver inflammation and liver fibrosis were improved after NAs or peginterferon-α therapy. In terms of improving the degree of liver inflammation, peginterferon-α therapy (74%) and NAs therapy (44%) were better than nonantiviral therapy (11%, p < 0.05), although no significant difference was shown between peginterferon-α therapy and NAs therapy (p = 0.974). For liver fibrosis improvement, peginterferon-α therapy showed significantly better efficacy than NAs therapy (68% vs. 33%, p = 0.044), while NAs therapy was better than nonantiviral therapy (33% vs. 11%, p = 0.028). Peginterferon-α and NAs can significantly improve the degree of liver inflammation and liver fibrosis in CHB patients. Peginterferon-α is superior to NAs in delaying and reversing liver fibrosis. This study provides a new basis for peginterferon-α therapy to prevent progression of fibrosis in CHB patients.
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Affiliation(s)
- Huiqing Liang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
- Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China
| | - Xiaoting Zheng
- Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China
| | - Yaoyu Liu
- Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China
| | - Qianguo Mao
- Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China
| | - Chuncheng Wu
- Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China
| | - Li Lin
- Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China
| | - Zhizhen Huang
- Fujian University of Traditional Chinese Medicine, Fujian, China
| | - Yue Chen
- Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China
| | - Manying Zhang
- Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China
| | - Luyun Zhang
- Fujian University of Traditional Chinese Medicine, Fujian, China
| | - Jia Min
- Fujian University of Traditional Chinese Medicine, Fujian, China
| | - Min Hu
- Fujian University of Traditional Chinese Medicine, Fujian, China
| | - Huiying Luo
- Fujian University of Traditional Chinese Medicine, Fujian, China
| | - Shaodong Chen
- School of Medicine, Xiamen University, Fujian, China
| | - Xiaohong Gu
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
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Tan Z, Kong N, Zhang Q, Gao X, Shang J, Geng J, You R, Wang T, Guo Y, Wu X, Zhang W, Qu L, Zhang F. Predictive model for HBsAg clearance rate in chronic hepatitis B patients treated with pegylated interferon α-2b for 48 weeks. Hepatol Int 2025; 19:358-367. [PMID: 39702655 PMCID: PMC12003487 DOI: 10.1007/s12072-024-10764-5] [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: 09/13/2024] [Accepted: 11/29/2024] [Indexed: 12/21/2024]
Abstract
BACKGROUND AND AIMS Chronic hepatitis B (CHB) is a major global health concern. This study aims to investigate the factors influencing hepatitis B surface antigen (HBsAg) clearance in CHB patients treated with pegylated interferon α-2b (Peg-IFNα-2b) for 48 weeks and to establish a predictive model. METHODS This analysis is based on the "OASIS" project, a prospective real-world multicenter study in China. We included CHB patients who completed 48 weeks of Peg-IFNα-2b treatment. Patients were randomly assigned to a training set and a validation set in a ratio of approximately 4:1 by spss 26.0, and were divided into clearance and non-clearance groups based on HBsAg status at 48 weeks. Clinical data were analyzed using SPSS 26.0, employing chi-square tests for categorical data and Mann-Whitney U tests for continuous variables. Significant factors (p < 0.05) were incorporated into a binary logistic regression model to identify independent predictors of HBsAg clearance. The predictive model's performance was evaluated using ROC curve analysis. RESULTS We included 868 subjects, divided into the clearance group (187 cases) and the non-clearance group (681 cases). They were randomly assigned to a training set (702 cases) and a validation set (166 cases). Key predictors included female gender (OR = 1.879), lower baseline HBsAg levels (OR = 0.371), and cirrhosis (OR = 0.438). The final predictive model was: Logit(P) = 0.92 + Gender (Female) * 0.66 - HBsAg (log) * 0.96 - Cirrhosis * 0.88. ROC analysis showed an AUC of 0.80 for the training set and 0.82 for the validation set, indicating good predictive performance. CONCLUSION Gender, baseline HBsAg levels, and cirrhosis are significant predictors of HBsAg clearance in CHB patients after 48 weeks of Peg-IFNα-2b therapy. The developed predictive model demonstrates high accuracy and potential clinical utility.
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Affiliation(s)
- Zhili Tan
- Department of Infectious Diseases, School of Medicine, Shanghai East Hospital, Tongji University, Shanghai, China
| | - Nan Kong
- Department of Infectious Diseases, School of Medicine, Shanghai East Hospital, Tongji University, Shanghai, China
| | - Qiran 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
| | - Xiaohong Gao
- Department of Infectious Diseases, Yanan University Affiliated Hospital, Yan'an, Shaanxi, China
| | - Jia Shang
- Department of Infectious Disease and Hepatic Disease, Henan Provincial People's Hospital, Henan, China
| | - Jiawei Geng
- Department of Infectious Disease and Hepatic Disease, First People's Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China
| | - Ruirui You
- 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
| | - Tao Wang
- Department of Infectious Diseases, School of Medicine, Shanghai East Hospital, Tongji University, Shanghai, China
| | - Ying Guo
- Deparment of Hepatology, The Third People's Hospital of Taiyuan, Taiyuan, China.
| | - Xiaoping Wu
- Department of Infectious Diseases, the First Affiliated Hospital of Nanchang University, Nanchang, 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.
| | - Lihong Qu
- Department of Infectious Diseases, School of Medicine, Shanghai East Hospital, Tongji University, Shanghai, China.
| | - Fengdi Zhang
- Department of Infectious Diseases, School of Medicine, Shanghai East Hospital, Tongji University, Shanghai, China.
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Wu F, Liu C, He L, Wang Y, Zhang X, Li M, Lu R, Kang P, Li M, Li Y, Jia X, Dang S. Peripheral Blood CD4 +/CD8 + T Cell Ratio Predicts HBsAg Clearance in Inactive HBsAg Carriers Treated with Peginterferon Alpha. J Clin Transl Hepatol 2025; 13:130-142. [PMID: 39917468 PMCID: PMC11797822 DOI: 10.14218/jcth.2024.00240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 10/22/2024] [Accepted: 11/05/2024] [Indexed: 02/09/2025] Open
Abstract
BACKGROUND AND AIMS T lymphocytes play a pivotal role in resolving hepatitis B virus infection. This study aimed to investigate the dynamics of peripheral blood T lymphocyte subsets during peginterferon alpha (peg-IFN-α) therapy and their association with hepatitis B surface antigen (HBsAg) clearance in inactive HBsAg carriers (IHCs). METHODS This prospective observational study enrolled 197 IHCs treated with peg-IFNα-2a/2b for 48 weeks and followed for 24 weeks (treatment group), and 221 IHCs who were regularly monitored for 72 weeks without treatment (IHC control group). Peripheral blood T lymphocyte subsets were evaluated using flow cytometry at baseline, and at 12, 24, 48, and 72 weeks in both groups. At 72 weeks, IHCs in the treatment group were categorized into an HBsAg clearance group and an HBsAg persistence group. Differences in T lymphocyte subsets among these groups were compared, and correlations between T lymphocyte subsets and HBsAg clearance were analyzed. RESULTS At 72 weeks, intention-to-treat analysis showed significantly higher HBsAg clearance (46.7%) and seroconversion rates (34.5%) in the treatment group compared to the IHC control group (HBsAg clearance rate of 1.4%, seroconversion rate of 0.9%; both p < 0.001). The median absolute counts of CD3+, CD4+, and CD8+ cells significantly decreased at 12, 24, and 48 weeks in both the HBsAg clearance and persistence groups, returning to baseline at 72 weeks (all p < 0.001). IHCs with HBsAg clearance had higher median percentages of CD3+ CD8+ cells and lower median percentages of CD3+ CD4+ cells and CD4+/CD8+ ratios at 12, 24, and 48 weeks compared to the HBsAg persistence and IHC control groups (all p < 0.001). Baseline HBsAg levels (below 2.0 log10 IU/mL) and hepatitis B virus DNA levels (below 20 IU/mL), alanine aminotransferase elevation at 12 weeks (greater than 2×upper limit of normal), and CD4+/CD8+ ratios (less than 1.5 at 12 weeks and below 1.4 at 24 weeks) were predictive of HBsAg clearance. CONCLUSIONS Peripheral blood CD4+/CD8+ ratios at 12 and 24 weeks may serve as predictive markers for HBsAg clearance in IHCs treated with peg-IFN-α.
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Affiliation(s)
- Fengping Wu
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Chenrui Liu
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Ling He
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Yikai Wang
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Xin Zhang
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Miaoxian Li
- Medical Laboratory, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Rui Lu
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Pei Kang
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Mei Li
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Yaping Li
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Xiaoli Jia
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Shuangsuo Dang
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
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Yan F, Tang F, Chen J, Lin Y, Chen X, Du Q, Yin W, Liang J, Liu L, Wang F, Xu B, Ye Q, Xiang H. Exploring using HBsAg to predict interferon treatment course to achieve clinical cure in chronic hepatitis B patients: a clinical study. Front Immunol 2025; 15:1528758. [PMID: 39867915 PMCID: PMC11758162 DOI: 10.3389/fimmu.2024.1528758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Accepted: 12/18/2024] [Indexed: 01/28/2025] Open
Abstract
Objective Although pegylated interferon α-2b (PEG-IFN α-2b) therapy for chronic hepatitis B has received increasing attention, determining the optimal treatment course remains challenging. This research aimed to develop an efficient model for predicting interferon (IFN) treatment course. Methods Patients with chronic hepatitis B, undergoing PEG-IFN α-2b monotherapy or combined with NAs (Nucleoside Analogs), were recruited from January 2018 to December 2023 at Tianjin Third Central Hospital. All patients achieved hepatitis B surface antigen (HBsAg) clearance post-treatment. Result The study enrolled 176 patients with chronic hepatitis B, with the median IFN treatment course of 35.23 ± 25.22 weeks. They were randomly divided into two cohorts in a ratio of 7:3. And there were 123 patients in the training cohort and 53 patients in the validation cohort. Univariable and multivariable analyses demonstrated that baseline HBsAg, 12 weeks HBsAg and the presence of cirrhosis significantly influenced IFN treatment course, and both are risk factors (β=7.27,4.27,10.91; p<0.05). After adjusting for confounding factors, HBsAg remained a significant predictor (β=6.99, 95%CI: 3.59,10.40; p<0.05), which was finally included to establish the model. The actual and predicted values in the validation cohort were highly matched, meanwhile the mean absolute percentage error (MAPE), root mean square error (RMSE) and accuracy (ACC) of the validation cohort were calculated. External validation also suggests that the model can be used as a tool for initial assessment. Conclusion Baseline HBsAg in chronic hepatitis B patients were a risk factor for prolonged IFN treatment course with a positive correlation. Ultimately, a personalized model based on baseline HBsAg levels can be established to roughly estimate the duration of interferon therapy prior to treatment initiation, thereby guiding clinical decision-making.
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Affiliation(s)
- Fei Yan
- The Third Central Clinical College of Tianjin Medical University, Tianjin Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin, China
| | - Fei Tang
- Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin, China
| | - Jing Chen
- The Third Central Clinical College of Tianjin Medical University, Tianjin Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin, China
| | - YiCheng Lin
- The Third Central Clinical College of Tianjin Medical University, Tianjin Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin, China
| | - XinYu Chen
- The Third Central Clinical College of Tianjin Medical University, Tianjin Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin, China
| | - Qin Du
- Nankai University Affiliated Third Center Hospital, Tianjin Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin, China
| | - WeiLi Yin
- Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin, China
| | - Jing Liang
- Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin, China
| | - Lei Liu
- Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin, China
| | - Fang Wang
- Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin, China
| | - BaiGuo Xu
- Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin, China
| | - Qing Ye
- Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin, China
| | - HuiLing Xiang
- Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Tianjin, China
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Lv YQ, Guo RH, Liu KY, Li JJ, Ji HF. Predictive factors for clinical cure in the treatment of HBeAg(-) chronic hepatitis B or compensated cirrhosis: a prospective observational study. Front Med (Lausanne) 2025; 11:1483744. [PMID: 39850101 PMCID: PMC11754238 DOI: 10.3389/fmed.2024.1483744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Accepted: 12/27/2024] [Indexed: 01/25/2025] Open
Abstract
Background Sequential or combined treatment with nucleos(t)ide analogs (NAs) and pegylated interferon alpha-2b (Peg-IFN-α-2b) can improve the clinical cure rate. However, its clinical application is limited due to the adverse reactions associated with IFN. Methods A multi-center prospective observational study was conducted involving 59 NAs-treated chronic hepatitis B (CHB) patients who were treated with a combination therapy of NAs and Peg-IFN-α-2b for 48 weeks. Another 327 NAs-treated patients received NAs monotherapy for 48 weeks. At the end of the treatment, patients were classified into either the clinically cured group or the non-clinically cured group based on clinical efficacy. The study aimed to analyze the clinical cure rate and the predictive factors. Results After propensity score matching (PSM), a total of 104 patients were included in the exposure and the control groups. After 48 weeks of treatment, 13 patients in the exposed group achieved clinical cure, with a cure rate of 25%. In contrast, in the control group was 1.92%. The clinical cure rate was greater in the population with CHB or compensated cirrhosis treated with sequential or combined Peg-IFN-α-2b and NAs than in the control group (p < 0.001). Patients treated with Peg-IFN-α-2b were divided into a clinical cure group and a non-clinical cure group for single-factor regression and multi-factor binary logistic regression. The results showed that baseline qHBsAg [relative ratio (RR) = 0.997, 95%CI: [0.995, 0.999], p = 0.031] and △TBiL (RR = 0.698, 95%CI: [0.555, 0.879], p = 0.002) were independent influencing factors for achieving clinical cure in patients with CHB or compensated cirrhosis. Conclusion A lower baseline qHBsAg and decrease in TBiL at 24 weeks of treatment are independent influencing factors for achieving clinical cure. The lower the baseline qHBsAg and the higher the △TBiL levels after 24 weeks of treatment, the higher the probability of patients achieving clinical cure.
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Affiliation(s)
| | | | | | | | - Hui-Fan Ji
- Department of Hepatobiliary and Pancreatic Medicine, The First Hospital of Jilin University Changchun, Changchun, Jilin, China
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8
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Peng Y, Ma M, Liu T, He W, Lin S, Zhong W, Min X. Predictors of HBsAg seroclearance in HBeAg-negative chronic hepatitis B patients treated with nucleotide analogs plus polyethylene glycol interferon. Front Med (Lausanne) 2025; 11:1510230. [PMID: 39845839 PMCID: PMC11751021 DOI: 10.3389/fmed.2024.1510230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Accepted: 12/23/2024] [Indexed: 01/24/2025] Open
Abstract
Introduction The minority of the chronic hepatitis B (CHB) patients received polyethylene glycol interferon (PEG-IFN) combined with nucleotide analogs (NAs) can obtain hepatitis B surface antigen (HBsAg) clearance. Methods In order to find out the advantaged population, we retrospectively collected 122 CHB patients treated with NAs alone or NAs plus PEG-IFN for 48 weeks, who were admitted to Sun Yat-sen Memorial Hospital from 2019 to 2024. Results We found HBsAg clearance rate in NAs plus PEG-IFN group was 40.98%, which was significantly higher than that in the NAs group. Thus, NAs plus PEG-IFN therapy served as a relatively ideal regimen and the patients received combined treatment were then incorporated for further analysis for searching efficacy predictors. Through using univariate and multivariate analysis, we confirmed the predictive value of HBsAg, alanine aminotransferase (ALT) at week 24, and ALT change values from baseline to week 24. The area under the receiver operating characteristic (ROC) curve of each indicators ranged from 0.663 to 0.982. Discussion In conclusion, our study verified the clinical value of NAs plus PEG-IFN for treating CHB patients. Moreover, for the first time, we found ALT change values from baseline to week 24 (dALT2) could act as a novel independent clinical efficacy predictors in the forementioned population.
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Affiliation(s)
- Yan Peng
- Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Mingzhe Ma
- Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Ting Liu
- Department of Infectious Disease, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Wenmin He
- Department of Gastroenterology, Shenshan Medical Center, Memorial Hospital of Sun Yat-sen University, Shanwei, China
| | - Shutao Lin
- Department of Infectious Diseases, Shenshan Medical Center, Memorial Hospital of Sun Yat-sen University, Shanwei, China
| | - Wa Zhong
- Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiaohui Min
- Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
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Zheng J, Wang Z, Huang L, Qiu Z, Xie Y, Jiang S, Feng B. Achieving chronic hepatitis B functional cure: Factors and potential mechanisms. Virus Res 2025; 351:199507. [PMID: 39662778 PMCID: PMC11699463 DOI: 10.1016/j.virusres.2024.199507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Revised: 08/20/2024] [Accepted: 12/03/2024] [Indexed: 12/13/2024]
Abstract
Chronic hepatitis B (CHB) is a significant global health issue affecting approximately 254 million individuals worldwide. Achieving the loss of hepatitis B surface antigen (HBsAg), either with or without seroconversion to hepatitis B surface antibody (HBsAb), is regarded as a functional cure and the optimal goal for addressing CHB, and can be achieved through various approaches, including induction with nucleos(t)ide analogues (NAs), induction with pegylated interferon alpha (PegIFNα), and spontaneous clearance of HBsAg. Spontaneous clearance of HBsAg is rare, while NAs can directly inhibit HBV DNA, they are unable to act on covalently closed circular DNA (cccDNA), hence inhibiting HBsAg production or clearing HBsAg is extremely challenging. On the other hand, functional cure based on PegIFNα shows good long-term durability, but over 10 % of patients still experience relapse, mostly within 48 weeks after functional cure. Factors related to CHB functional cure with antiviral therapy are complex, including host factors, viral factors, environmental factors, etc. The integration of HBV DNA into liver cells, persistence of HBV cccDNA, insufficient B cell responses and compromised T cell function pose significant barriers to HBV clearance. Therefore, this study systematically reviewed the relevant factors and potential mechanisms influencing functional cure CHB, which can provide a basis for personalized treatment, help predict treatment outcomes and assess prognosis, and provide theoretical support for the advancement of novel treatment strategies and medications.
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Affiliation(s)
- Jiarui Zheng
- Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China
| | - Zilong Wang
- Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China
| | - Linxiang Huang
- Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China
| | - Zixuan Qiu
- Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China
| | - Yandi Xie
- Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China
| | - Suzhen Jiang
- Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China
| | - Bo Feng
- Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China.
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Ye YM, Lin Y, Sun F, Yang WY, Zhou L, Lin C, Pan C. A predictive model for functional cure in chronic HBV patients treated with pegylated interferon alpha: a comparative study of multiple algorithms based on clinical data. Virol J 2024; 21:333. [PMID: 39710712 PMCID: PMC11665216 DOI: 10.1186/s12985-024-02599-1] [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: 10/08/2024] [Accepted: 12/04/2024] [Indexed: 12/24/2024] Open
Abstract
BACKGROUND A multivariate predictive model was constructed using baseline and 12-week clinical data to evaluate the rate of clearance of hepatitis B surface antigen (HBsAg) at the 48-week mark in patients diagnosed with chronic hepatitis B who are receiving treatment with pegylated interferon α (PEG-INFα). METHODS The study cohort comprised CHB patients who received pegylated interferon treatment at Mengchao Hepatobiliary Hospital, Fujian Medical University, between January 2019 and April 2024. Predictor variables were identified (LASSO), followed by multivariate analysis and logistic regression analysis. Subsequently, predictive models were developed via logistic regression, random forest (RF), gradient boosting decision tree (GBDT), extreme gradient boosting (XGBoost), and support vector machine (SVM) algorithms. The efficacy of these models was assessed through various performance metrics, including the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and F1 score. RESULTS This study included a total of 224 individuals diagnosed with chronic hepatitis B. The variables baseline log2(HBsAg), gender, age, neutrophil count at week 12, HBsAg decline rate at week 12, and HBcAb at week 12 were closely associated with functional cure and were included in the predictive model. In the validation term, the logistic regression model had an AUC of 0.858, which was better than that of the other machine learning models (AUC = 0.858,F1 = 0.753). Consequently, this model was selected for the development of the predictive tool. CONCLUSIONS The combined use of the baseline log2(HBsAg) value, HBsAg decline rate at week 12, gender, neutrophil count at week 12, and age can serve as a foundational predicting model for anticipating the clearance of HBsAg in individuals with chronic hepatitis B who are receiving PEG-INFα therapy.
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Affiliation(s)
- Ya-Mei Ye
- Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, 350000, China
| | - Yong Lin
- Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, 350000, China
| | - Fang Sun
- Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, 350000, China
| | - Wen-Yan Yang
- Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, 350000, China
| | - Lina Zhou
- Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, 350000, China
| | - Chun Lin
- Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, 350000, China.
| | - Chen Pan
- Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, 350000, China.
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11
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Wang Z, Wang X, Zhou L, Shi S, Hua Y, Feng Y. Safety and efficacy of 48-week pegylated interferon- α-2b therapy in patients with hepatitis B virus-related compensated liver cirrhosis: a pilot observational study. Front Med (Lausanne) 2024; 11:1489671. [PMID: 39697201 PMCID: PMC11652151 DOI: 10.3389/fmed.2024.1489671] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Accepted: 11/25/2024] [Indexed: 12/20/2024] Open
Abstract
Background Pegylated interferon-α (PEG-IFN-α) therapy could decrease hepatitis B surface antigen (HBsAg) and improve long-term prognosis of hepatitis B virus (HBV) infection. However, studies on safety and efficacy of PEG-IFN-α for patients with HBV-related cirrhosis are limited. Methods This was a single-center study. Fifty-four patients with HBV-related compensated cirrhosis were enrolled. All patients received subcutaneous injection of PEG-IFN-α-2b 180 μg per week for 48 weeks. The monotherapy of PEG-IFN-α-2b was used for treatment-naïve patients, while addition of PEG-IFN-α-2b to on-going nucleos(t)ide analogs (NAs) was used for NAs-experienced patients. Clinical symptoms, laboratory tests, examination indicators, and adverse events were collected at each observational time point. Results Forty-two patients achieved undetectable serum HBV DNA at 48 weeks post-therapy. HBsAg level was significantly reduced at 48 weeks post-therapy (227.2 IU/mL vs. 1,668 IU/mL; p < 0.001), especially in NAs-experienced patients (161.0 IU/mL vs. 1,207 IU/mL; p = 0.005). Three patients achieved HBsAg loss, and two of them obtained HBsAg seroconversion. There were no significant differences in liver stiffness measurement, thickness and length of spleen, or diameter of portal vein between baseline and 48 weeks post-therapy (p > 0.05). The aminotransferase levels were increased, while white blood cells, neutrophils, and platelets counts were decreased during PEG-IFN-α-2b therapy (p < 0.05), especially in treatment-naïve patients. Three patients discontinued PEG-IFN-α-2b therapy due to severe adverse events. No patients suffered with virological breakthrough or progressed to end-stage liver diseases during observational period. Conclusion A finite course of PEG-IFN-α-2b therapy was well-tolerated, and reduced HBsAg level without accelerating disease progression in patients with HBV-related compensated cirrhosis. Clinical trial registration This trial is a part of ZhuFeng Project (ClinicalTrials.gov, identifier NCT04035837).
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Yuen MF, Lim YS, Yoon KT, Lim TH, Heo J, Tangkijvanich P, Tak WY, Thanawala V, Cloutier D, Mao S, Arizpe A, Cathcart AL, Gupta SV, Hwang C, Gane E. VIR-2218 (elebsiran) plus pegylated interferon-alfa-2a in participants with chronic hepatitis B virus infection: a phase 2 study. Lancet Gastroenterol Hepatol 2024; 9:1121-1132. [PMID: 39389081 DOI: 10.1016/s2468-1253(24)00237-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 07/19/2024] [Accepted: 07/20/2024] [Indexed: 10/12/2024]
Abstract
BACKGROUND Chronic hepatitis B virus (HBV) remains a global concern, with current treatments achieving low rates of HBsAg seroclearance. VIR-2218 (elebsiran), a small interfering RNA agent against HBV transcripts, reduces HBsAg concentrations. We aimed to evaluate the safety and antiviral activity of VIR-2218 with and without pegylated interferon-alpha-2a treatment in participants with chronic HBV. METHODS This open-label, phase 2 study was conducted at 23 sites in six countries (New Zealand, Australia, Hong Kong, Thailand, South Korea, and Malaysia). Adults (aged 18-65 years) with chronic HBV infection without cirrhosis and with HBsAg more than 50 IU/mL and HBV DNA less than 90 IU/mL who were on continued nucleoside or nucleotide reverse transcriptase inhibitor (NRTI) therapy for 2 months or longer were eligible. Participants were enrolled into one of six cohorts to receive VIR-2218 200 mg subcutaneously every 4 weeks, with or without 180 μg subcutaneous pegylated interferon-alfa-2a once per week. Cohort 1 received six doses of VIR-2218 (total 20 weeks); cohort 2 received six doses of VIR-2218 starting at day 1, plus 12 doses of pegylated interferon-alfa-2a starting at week 12 (total 24 weeks); cohort 3 received six doses of VIR-2218 and 24 doses of pegylated interferon-alfa-2a (total 24 weeks); cohort 4 received six doses of VIR-2218 and up to 48 doses of pegylated interferon-alfa-2a (total 48 weeks); cohort 5 received up to 13 doses of VIR-2218 and up to 44 doses of pegylated interferon-alfa-2a (total 48 weeks); and cohort 6 received three doses of VIR-2218 and 12 doses of pegylated interferon-alfa-2a (total 12 weeks). The primary endpoints were the incidence of adverse events and clinical assessments (including results of laboratory tests). Secondary endpoints were the mean maximum reduction of serum HBsAg at any timepoint; the proportion of participants with serum HBsAg seroclearance at any timepoint and for more than 6 months after the end of treatment; and the proportion of participants with anti-HBs seroconversion at any timepoint. For patients who were HBeAg-positive, we also assessed the proportion with HBeAg seroclearance or anti-HBe seroconversion at any timepoint. This study is registered with ClinicalTrials.gov, NCT03672188, and is ongoing. FINDINGS Between July 2, 2020, and Nov 2, 2021, 124 individuals were screened for eligibility, 84 of whom were enrolled (15 in cohort 1, 15 in cohort 2, 18 in cohort 3, 18 in cohort 4, 13 in cohort 5, and five in cohort 6). Participants were predominantly HBeAg-negative, Asian, and male (66 [79%] participants were male and 18 [21%] were female). Most treatment emergent adverse events were grades 1-2. Three (20%) participants in cohort 1, four (27%) in cohort 2, eight (44%) in cohort 3, seven (39%) in cohort 4, six (46%) in cohort 5, and two (40%) in cohort 6 reported treatment-emergent adverse events related to VIR-2218. 12 (80%) participants in cohort 2, 12 (67%) in cohort 3, 14 (78%) in cohort 4, 13 (100%) in cohort 5, and three (60%) in cohort 6 reported treatment-emergent adverse events related to pegylated interferon-alfa-2a. Two (13%) participants in cohort 1 had elevations in alanine aminotransferase, compared with 13 (87%) participants in cohort 2, 15 (83%) in cohort 3, 17 (94%) in cohort 4, 11 (85%) in cohort 5, and three (60%) in cohort 6. The mean maximum change from baseline at any timepoint in HBsAg concentration was -2·0 log10 IU/mL (95% CI -2·1 to -1·8) in cohort 1, -2·2 log10 IU/mL (-2·5 to -1·8) in cohort 2, -2·5 log10 IU/mL (-2·8 to -2·1) in cohort 3, -2·4 log10 IU/mL (-3·1 to -1·8) in cohort 4, -3·0 log10 IU/mL (-3·7 to -2·3) in cohort 5, and -1·7 log10 IU/mL (-2·1 to -1·4) in cohort 6. 11 participants (one in cohort 2, one in cohort 3, five in cohort 4, and four in cohort 5) receiving VIR-2218 plus pegylated interferon-alfa-2a had HBsAg seroclearance at any timepoint. Of these, ten (91%; one in cohort 2, five in cohort 4, and four in cohort 5) had anti-HBs seropositivity. Six participants (one in cohort 2, three in cohort 4, and two in cohort 5) had sustained HBsAg seroclearance through to 24 weeks after the end of treatment. No participants receiving VIR-2218 monotherapy (cohort 1) or VIR-2218 plus pegylated interferon-alfa-2a 12-week regimen (cohort 6) had HBsAg seroclearance. 12 (42%) of 26 participants (one of four in cohort 1, two of six in cohort 2, four of seven in cohort 3, four of six in cohort 4, and one of three in cohort 5) who were HBeAg positive at baseline had HBeAg seroclearance or anti-HBe seroconversion. INTERPRETATION The results of this phase 2 study support further development of VIR-2218 as a potential therapy for patients with chronic HBV infection. Additional clinical trials of VIR-2218 with and without pegylated interferon-alfa-2a in combination with an HBsAg-targeting monoclonal antibody are ongoing. FUNDING Vir Biotechnology.
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Affiliation(s)
- Man-Fung Yuen
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong Special Administrative Region, China.
| | - Young-Suk Lim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Ki Tae Yoon
- Liver Center, Pusan National University Yangsan Hospital, Yangsan, South Korea; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Pusan National University College of Medicine, Yangsan, South Korea
| | - Tien-Huey Lim
- Department of Gastroenterology and Hepatology, Middlemore Hospital, Auckland, New Zealand
| | - Jeong Heo
- Department of Internal Medicine, College of Medicine, Pusan National University and Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
| | - Pisit Tangkijvanich
- Center of Excellence in Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Won Young Tak
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine Kyungpook National University, Daegu, South Korea
| | | | | | | | | | | | | | | | - Edward Gane
- Department of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
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Wang J, Zhang Z, Zhu L, Zhang Q, Zhang S, Pan Y, Liu J, Cao F, Fan T, Xiong Y, Yin S, Yan X, Chen Y, Zhu C, Li J, Liu X, Wu C, Huang R. Association of hepatitis B core antibody level and hepatitis B surface antigen clearance in HBeAg-negative patients with chronic hepatitis B. Virulence 2024; 15:2404965. [PMID: 39317345 PMCID: PMC11423664 DOI: 10.1080/21505594.2024.2404965] [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: 01/31/2024] [Revised: 08/15/2024] [Accepted: 09/05/2024] [Indexed: 09/26/2024] Open
Abstract
Predicting hepatitis B surface antigen (HBsAg) clearance is important for chronic hepatitis B (CHB) patients receiving pegylated interferon-alfa (Peg-IFN) therapy. We aimed to determine the predictive value of serum hepatitis B core antibody (anti-HBc) for HBsAg clearance. A total of 189 HBeAg-negative CHB patients who received Peg-IFN based therapy were retrospectively included and classified into two groups: nucleos(t)ide analogues (NAs) add-on Peg-IFN group (add-on group, n = 94) and Peg-IFN combined with NAs or Peg-IFN monotherapy group (combination or monotherapy group, n = 95). After 48 weeks of treatment, 27.5% (52/189) and 15.9% (30/189) of patients achieved HBsAg clearance and seroconversion, respectively. Patients in the combination or monotherapy group tended to achieve relatively higher HBsAg clearance (31.6% vs. 23.4%, p = 0.208) and seroconversion (21.1% vs. 10.6%, p = 0.050) rates than those in the add-on group. In combination or monotherapy group, anti-HBc levels at week 12 were lower in patients with HBsAg clearance (9.0 S/CO vs. 9.9 S/CO, p < 0.001) and seroconversion (8.8 S/CO vs. 9.8 S/CO, p < 0.001) than those without. Anti-HBc level at week 12 was an independent predictor of HBsAg clearance and seroconversion. Patients with lower anti-HBc levels at week 12 showed a more significant decline in HBsAg levels during treatment. Combination of anti-HBc at week 12 and baseline HBsAg could identify over 70% of patients who achieved HBsAg clearance after 48 weeks of treatment. In addition to HBsAg, anti-HBc level could be used as a promising marker for selecting HBeAg-negative CHB patients who are more likely to respond to Peg-IFN-based therapy.
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Affiliation(s)
- Jian Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Zhiyi Zhang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Li Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Qing Zhang
- Department of Infectious Diseases, Huai’an No. 4 People’s Hospital, Huai’an, Jiangsu, China
| | - Shaoqiu Zhang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Yifan Pan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Jiacheng Liu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Fei Cao
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Tao Fan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Ye Xiong
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Shengxia Yin
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Xiaomin Yan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Yuxin Chen
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Chuanwu Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Jie Li
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Xingxiang Liu
- Department of Clinical Laboratory, Huai’an No. 4 People’s Hospital, Huai’an, Jiangsu, China
| | - Chao Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Rui Huang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
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Xu S, Ye XT, Zhang D, Dong P, Wu YH, Pan CW. Predicting clinical outcomes in chronic hepatitis B patients receiving nucleoside analogues and pegylated interferon alpha: a hematochemical and clinical analysis. BMC Infect Dis 2024; 24:1149. [PMID: 39396949 PMCID: PMC11472561 DOI: 10.1186/s12879-024-10057-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Accepted: 10/03/2024] [Indexed: 10/15/2024] Open
Abstract
BACKGROUND The best antiviral treatment for chronic hepatitis B (CHB) poses a complex challenge. The treatment effect of the combination of nucleoside analogues (NAs) and pegylated interferon alpha (PegIFN) was still in debate. METHODS We studied patients treated with NAs and PegIFN-2b at our institution from November 2019 to January 2022. Logistic regression identified independent factors influencing clinical cure. The predictive accuracy of the formula was assessed using the Receiver operating characteristic (ROC) curve at different time points (before therapy, 12 weeks, and 24 weeks into treatment). RESULTS A total of 120 patients were enrolled in the final analysis. Among the cohort of patients under study, 71 (59.1%) patients had clinical cure while 49 (40.9%) patients did not. Hepatitis B surface antigen (HBsAg) at baseline and age were the powerful variables predicting the clearance of HBsAg. The area under the ROC (AUC) was 0.907 for pre-treatment predictive model, 0.958 for 12-week predictive model and 0.747 for 24-week predictive model. CONCLUSION This study provided predictive formulas for clinical cure, offering valuable insights for CHB treatment. PegIFN and NAs exhibited efficacy. Future research that explores additional factors, such as HBV genotype, in a larger cohort study is needed.
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Affiliation(s)
- Shuang Xu
- Department of infectious Diseases, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Xiao-Ting Ye
- Department of infectious Diseases, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Dong Zhang
- Department of infectious Diseases, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Pu Dong
- Department of infectious Diseases, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Yang-He Wu
- Department of infectious Diseases, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Chen-Wei Pan
- Department of infectious Diseases, The Second Affiliated Hospital and Yuying Children's Hospital, of Wenzhou Medical University, Wenzhou, China.
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Li Y, Yang S, Li C, Ma Z, Zhang M, Zou W, Wu Z, Hou H, Wang W, Zhu L. Efficacy of short-term Peg-IFN α-2b treatment in chronic hepatitis B patients with ultra-low HBsAg levels: a retrospective cohort study. Virol J 2024; 21:231. [PMID: 39334422 PMCID: PMC11428405 DOI: 10.1186/s12985-024-02512-w] [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: 06/17/2024] [Accepted: 09/19/2024] [Indexed: 09/30/2024] Open
Abstract
PURPOSE Peginterferon alfa-2b (Peg-IFN α-2b) has demonstrated superior efficacy over nucleos(t)ide analogs (NAs) in the treatment of chronic hepatitis B (CHB), particularly among patients with low levels of hepatitis B surface antigen (HBsAg). This study aims to determine whether patients with ultra-low HBsAg levels (< 200 IU/mL) can achieve significantly higher clinical cure rates with abbreviated courses of Peg-IFN α-2b therapy. METHODS In this retrospective analysis, CHB patients with HBsAg levels below 200 IU/mL were categorized into a Peg-IFN α-2b group and a control group. The Peg-IFN α-2b group received Peg-IFN α-2b for a minimum of 24 weeks, with the possibility of early discontinuation upon achieving HBsAg clearance, and were followed through week 48. The control group remained untreated for hepatitis B virus (HBV), and was observed for 24 weeks. HBsAg clearance rates were compared between groups. Univariate and multivariate logistic regression analyses were employed to identify factors associated with HBsAg clearance . RESULTS By week 24, the HBsAg clearance rate in the Peg-IFN α-2b group was notably 52.1% (38/73), contrasting sharply with the mere 1.3% (1/77) observed in the control group. Within the Peg-IFN α-2b group, a substantial 97.3% (71/73) of patients noted a reduction in HBsAg levels. Besides, the decision to continue or discontinue treatment after the 24-week mark had no significant impact on the HBsAg clearance rate at week 48. Multivariable analysis pinpointed baseline HBsAg levels (OR = 0.984, p = 0.001) and the presence of fatty liver (OR = 5.960, p = 0.033) as independent predictors of HBsAg clearance. CONCLUSION Our findings confirm that a 24-week course of Peg-IFN α-2b yields robust efficacy in CHB patients with ultra-low HBsAg levels. Prolonging treatment beyond the 24-week threshold is deemed unnecessary. Both baseline HBsAg level and the presence of fatty liver emerged as significant predictors for HBsAg clearance.
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Affiliation(s)
- Yuying Li
- Department of Infectious Diseases, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, Heilongjiang, China
| | - Siqi Yang
- Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan, 430062, Hubei, China
| | - Cong Li
- Department of Urology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China
| | - Zhenjie Ma
- Department of Infectious Diseases, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, Heilongjiang, China
| | - Mengmeng Zhang
- Department of Infectious Diseases, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, Heilongjiang, China
| | - Wenhang Zou
- Department of Infectious Diseases, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, Heilongjiang, China
| | - Zihao Wu
- Department of Infectious Diseases, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, Heilongjiang, China
| | - Haiyan Hou
- Department of Infectious Diseases, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, Heilongjiang, China
| | - Weixing Wang
- Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan, 430062, Hubei, China.
| | - Liying Zhu
- Department of Infectious Diseases, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, Heilongjiang, China.
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Zhong W, Yan L, Zhu Y, Shi L, He Y, Chen T, Zheng J. A high functional cure rate was induced by pegylated interferon alpha-2b treatment in postpartum hepatitis B e antigen-negative women with chronic hepatitis B virus infection: an exploratory study. Front Cell Infect Microbiol 2024; 14:1426960. [PMID: 39176265 PMCID: PMC11338904 DOI: 10.3389/fcimb.2024.1426960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Accepted: 07/24/2024] [Indexed: 08/24/2024] Open
Abstract
Background and aims Limited data have been reported on achieving functional cure using pegylated interferon (Peg-IFN) alpha-2b treatment for postpartum hepatitis B e antigen (HBeAg)-negative women with chronic hepatitis B virus (HBV) infection. This study was to assess the effectiveness and safety of Peg-IFN alpha-2b in HBV postpartum women without HBeAg and identify factors linked to the functional cure. Methods A total of 150 HBeAg-negative postpartum women were retrospectively recruited.47 patients received Peg-IFN alpha-2b [Peg-IFN(+) group] and 103 patients did not [Peg-IFN(-) group]. Propensity score matching (PSM) was used to adjust the baseline imbalance between the two groups. The patients were followed for at least 48 weeks. The primary endpoints were hepatitis B surface antigen(HBsAg) loss and HBsAg seroconversion at 48 weeks. Logistic regression analysis was used to assess factors associated with HBsAg loss at 48 weeks. Results At week 48,the HBsAg loss and seroconversion rate in Peg-IFN(+) group were 51.06%(24/47) and 40.43%(19/47), respectively. Even after PSM, Peg-IFN(+) group still showed higher HBsAg loss rate (50.00% vs 7.14%,p<0.001) and higher HBsAg seroconversion rate (38.10% vs 2.38%,p<0.001). Baseline HBsAg levels (Odds Ratio [OR]: 0.051, 95% Confidence Interval [CI]: 0.003-0.273, P=0.010), HBsAg at week 24 (OR:0.214, 95%CI:0.033-0.616, P=0.022), HBsAg decline at week 24 (OR:4.682, 95%CI: 1.624-30.198, P=0.022) and postpartum flare (OR:21.181, 95%CI:1.872-633.801, P=0.030) were significantly associated with HBsAg loss at week 48 after Peg-IFN alpha-2b therapy. Furthermore, the receiver operating characteristic curve (ROC) showed that the use of baseline HBsAg<182 IU/mL, HBsAg at week24 < 4 IU/mL and HBsAg decline at week24>12IU/mL were good predictors of HBsAg loss. No serious adverse events were reported. Conclusion Peg-IFN alpha-2b treatment could achieve a high rate of HBsAg loss and seroconversion in HBeAg-negative postpartum women with reliable safety, particularly for patients experience postpartum flare and have low baseline HBsAg levels.
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Affiliation(s)
- Wenting Zhong
- Department of Infectious Disease, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Lanzhi Yan
- Department of Infectious Disease, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Yage Zhu
- Department of Infectious Disease, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Lei Shi
- Department of Infectious Disease, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Yingli He
- Department of Infectious Disease, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Tianyan Chen
- Department of Infectious Disease, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Jie Zheng
- Department of Radiology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
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17
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Zhang PX, Tang QQ, Zhu J, Deng WY, Zhang ZH. Predictive models for functional cure in patients with CHB receiving PEG-IFN therapy based on HBsAg quantification through meta-analysis. Hepatol Int 2024; 18:1110-1121. [PMID: 38913149 DOI: 10.1007/s12072-024-10666-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Accepted: 02/25/2024] [Indexed: 06/25/2024]
Abstract
BACKGROUND AND AIMS The efficacy of achieving HBsAg clearance through pegylated interferon (PEG-IFNα) therapy in patients with chronic hepatitis B (CHB) remains uncertain, especially regarding the probability of achieving functional cure among patients with varying baseline HBsAg levels. We aimed to investigate the predictive value of HBsAg quantification for HBsAg seroclearance in CHB patients undergoing PEG-IFNα treatment. METHODS A systematic search was conducted in PubMed, Embase, and the Cochrane Library up to January 11, 2022. Subgroup analyses were performed for HBeAg-positive and HBeAg-negative patients, PEG-IFNα monotherapy and PEG-IFNα combination therapy, treatment-naive and treatment-experienced patients, and patients with or without liver cirrhosis. RESULTS This predictive model incorporated 102 studies. The overall HBsAg clearance rates at the end of treatment (EOT) and the end of follow-up (EOF) were 10.6% (95% CI 7.8-13.7%) and 11.1% (95% CI 8.4-14.1%), respectively. Baseline HBsAg quantification was the most significant factor. According to the model, it is projected that when baseline HBsAg levels are 100, 500, 1500, and 10,000 IU/ml, the HBsAg clearance rates at EOF could reach 53.9% (95% CI 40.4-66.8%), 32.1% (95% CI 24.8-38.7%), 14.2% (95% CI 9.8-18.8%), and 7.9% (95% CI 4.2-11.8%), respectively. Additionally, treatment-experienced patients with HBeAg-negative status, and without liver cirrhosis exhibited higher HBsAg clearance rates after PEG-IFNα treatment. CONCLUSION A successful predictive model has been established to predict the achievement of functional cure in CHB patients receiving PEG-IFNα therapy.
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Affiliation(s)
- Pei-Xin Zhang
- Department of Infectious Diseases, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei, 230601, China
| | - Qian-Qian Tang
- Department of Infectious Diseases, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei, 230601, China
| | - Jie Zhu
- Department of Infectious Diseases, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei, 230601, China
| | - Wan-Yu Deng
- College of Life Science, Shangrao Normal University, Shangrao, China
| | - Zhen-Hua Zhang
- Department of Infectious Diseases, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei, 230601, China.
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18
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Li YP, Liu CR, He L, Dang SS. Hepatitis B cure: Current situation and prospects. World J Hepatol 2024; 16:900-911. [PMID: 38948438 PMCID: PMC11212658 DOI: 10.4254/wjh.v16.i6.900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Revised: 05/05/2024] [Accepted: 06/03/2024] [Indexed: 06/20/2024] Open
Abstract
Achievement of a 'clinical cure' in chronic hepatitis B (CHB) implies sustained virological suppression and immunological control over the infection, which is the ideal treatment goal according to domestic and international CHB management guidelines. Clinical practice has shown encouraging results for specific patient cohorts using tailored treatment regimens. These regimens incorporate either nucleos(t)ide analogs, immunomodulatory agents such as pegylated interferon α, or a strategic combination of both, sequentially or concurrently administered. Despite these advancements in the clinical handling of hepatitis B, achieving a clinical cure remains elusive for a considerable subset of patients due to the number of challenges that preclude the realization of optimal treatment outcomes. These include, but are not limited to, the emergence of antiviral resistance, incomplete immune recovery, and the persistence of covalently closed circular DNA. Moreover, the variance in response to interferon therapy and the lack of definitive biomarkers for treatment cessation also contribute to the complexity of achieving a clinical cure. This article briefly overviews the current research progress and existing issues in pursuing a clinical cure for hepatitis B.
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Affiliation(s)
- Ya-Ping Li
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
| | - Chen-Rui Liu
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
| | - Ling He
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
| | - Shuang-Suo Dang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
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Jiang S, Guo S, Huang Y, Yin Y, Feng J, Zhou H, Guo Q, Wang W, Xin H, Xie Q. Predictors of HBsAg seroclearance in patients with chronic HBV infection treated with pegylated interferon-α: a systematic review and meta-analysis. Hepatol Int 2024; 18:892-903. [PMID: 38461186 PMCID: PMC11126512 DOI: 10.1007/s12072-024-10648-8] [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: 10/07/2023] [Accepted: 01/22/2024] [Indexed: 03/11/2024]
Abstract
BACKGROUND AND AIMS The identification of reliable predictors for hepatitis B surface antigen (HBsAg) seroclearance remains controversial. We aimed to summarize potential predictors for HBsAg seroclearance by pegylated interferon-α (PegIFNα) in patients with chronic HBV infection. METHODS A systematic search of the Cochrane Library, Embase, PubMed, and Web of Science databases was conducted from their inception to 28 September 2022. Meta-analyses were performed following the PRISMA statement. Predictors of HBsAg seroclearance were evaluated based on baseline characteristics and on-treatment indicators. RESULTS This meta-analysis encompasses 27 studies, including a total of 7913 patients. The findings reveal several factors independently associated with HBsAg seroclearance induced by PegIFNα-based regimens. These factors include age (OR = 0.961), gender (male vs. female, OR = 0.537), genotype (A vs. B/D; OR = 7.472, OR = 10.738), treatment strategy (combination vs. monotherapy, OR = 2.126), baseline HBV DNA (OR = 0.414), baseline HBsAg (OR = 0.373), HBsAg levels at week 12 and 24 (OR = 0.384, OR = 0.294), HBsAg decline from baseline to week 12 and 24 (OR = 6.689, OR = 6.513), HBsAg decline from baseline ≥ 1 log10 IU/ml and ≥ 0.5 log10 IU/ml at week 12 (OR = 18.277; OR = 4.530), and ALT elevation at week 12 (OR = 3.622). Notably, subgroup analysis suggests no statistical association between HBsAg levels at week 12 and HBsAg seroclearance for treatment duration exceeding 48 weeks. The remaining results were consistent with the overall analysis. CONCLUSIONS This is the first meta-analysis to identify predictors of HBsAg seroclearance with PegIFNα-based regimens, including baseline and on-treatment factors, which is valuable in developing a better integrated predictive model for HBsAg seroclearance to guide individualized treatment and achieve the highest cost-effectiveness of PegIFNα.
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Affiliation(s)
- Shaowen Jiang
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Simin Guo
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yan Huang
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yalin Yin
- School of Life Sciences, Xiamen University, Xiamen, China
| | - Jingwen Feng
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Huijuan Zhou
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qing Guo
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weijing Wang
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- Department of Infectious Diseases, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Haiguang Xin
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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20
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Leowattana W, Leowattana P, Leowattana T. Quantitative hepatitis B core antibody and quantitative hepatitis B surface antigen: Novel viral biomarkers for chronic hepatitis B management. World J Hepatol 2024; 16:550-565. [PMID: 38689745 PMCID: PMC11056893 DOI: 10.4254/wjh.v16.i4.550] [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: 12/12/2023] [Revised: 02/03/2024] [Accepted: 03/12/2024] [Indexed: 04/24/2024] Open
Abstract
The management of hepatitis B virus (HBV) infection now involves regular and appropriate monitoring of viral activity, disease progression, and treatment response. Traditional HBV infection biomarkers are limited in their ability to predict clinical outcomes or therapeutic effectiveness. Quantitation of HBV core antibodies (qAnti-HBc) is a novel non-invasive biomarker that may help with a variety of diagnostic issues. It was shown to correlate strongly with infection stages, hepatic inflammation and fibrosis, chronic infection exacerbations, and the presence of occult infection. Furthermore, qAnti-HBc levels were shown to be predictive of spontaneous or treatment-induced HBeAg and HBsAg seroclearance, relapse after medication termination, re-infection following liver transplantation, and viral reactivation in the presence of immunosuppression. qAnti-HBc, on the other hand, cannot be relied on as a single diagnostic test to address all problems, and its diagnostic and prognostic potential may be greatly increased when paired with qHBsAg. Commercial qAnti-HBc diagnostic kits are currently not widely available. Because many methodologies are only semi-quantitative, comparing data from various studies and defining universal cut-off values remains difficult. This review focuses on the clinical utility of qAnti-HBc and qHBsAg in chronic hepatitis B management.
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Affiliation(s)
- Wattana Leowattana
- Department of Clinical Tropical Medicine, Mahidol University, Rachatawee 10400, Bangkok, Thailand.
| | - Pathomthep Leowattana
- Department of Clinical Tropical Medicine, Mahidol University, Rachatawee 10400, Bangkok, Thailand
| | - Tawithep Leowattana
- Department of Medicine, Srinakharinwirot University, Wattana 10110, Bangkok, Thailand
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Wen C, Wang Y, Tian H, Lei Y, Wang Z, Cai D, Zhou Z, Shi X. Clinical cure induced by pegylated interferon α-2b in the advantaged population of chronic hepatitis B virus infection: a retrospective cohort study. Front Cell Infect Microbiol 2024; 13:1332232. [PMID: 38292859 PMCID: PMC10824921 DOI: 10.3389/fcimb.2023.1332232] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Accepted: 12/22/2023] [Indexed: 02/01/2024] Open
Abstract
Background Among the advantaged population with clinical cure of chronic hepatitis B, chronic inactive hepatitis B virus carriers (IHCs) and nucleoside analog-experienced patients have similar serological manifestations. This study established non-interferon-treated groups as controls to compare the efficacy of pegylated interferon α-2b (Peg-IFNα-2b) in achieving clinical cure between IHCs and nucleoside analog (NA)-experienced patients. Method A total of 270 patients were enrolled in this observational study. The IHC cohort comprised 55 patients who received Peg-IFNα-2b (Peg-IFN group), and the other 70 patients did not receive any antiviral treatment (untreated group). Patients treated with NAs were divided into two groups: one group (70 patients) receiving NA add-on Peg-IFNα-2b therapy regimen (NA add-on Peg-IFN group) and another group (75 patients) receiving continuous NA monotherapy (NA group). The primary endpoints were hepatitis B surface antigen (HBsAg) clearance and HBsAg seroconversion at 48 weeks and 72 weeks. Results At 48 weeks, 65.5% (36/55) and 52.9% (37/70) patients achieved HBsAg clearance in the Peg-IFN group and NA add-on Peg-IFN group, respectively (p = 0.156). HBsAg seroconversion was achieved in 47.3% (26/55) of the Peg-IFN group and 34.3% (24/70) of the NA add-on Peg-IFN group (p = 0.141). At the follow-up of 72 weeks, 36 patients in the Peg-IFN group achieved HBsAg loss (65.5%, 36/55), and 33 patients in the NA add-on Peg-IFN group achieved HBsAg clearance (47.1%, 33/70), which were significantly higher than in the Peg-IFN group (p = 0.041). The HBsAg seroconversion rates in the Peg-IFN group and NA add-on Peg-IFN group at 72 weeks were 45.5% (25/55) and 32.9% (23/70), respectively (p = 0.151). No patient achieved HBsAg clearance or seroconversion in the NA group and untreated group. Furthermore, the receiver operating characteristic curve showed baseline HBsAg< 72 IU/mL, and the decline of HBsAg of more than 80% and 98% from baseline to 12 and 24 weeks provided good predictions for HBsAg clearance. Meanwhile, 77% of patients with baseline HBsAg< 100 IU/mL achieved a clinical cure at 48 weeks. Conclusion Peg-IFNα-2b results in a high rate of HBsAg clearance and seroconversion in both IHCs and NA-experienced patients, especially for those patients who have HBsAg below 100 IU/mL.
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Affiliation(s)
| | | | | | | | | | | | | | - Xiaofeng Shi
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Mimura S, Fujita K, Takuma K, Nakahara M, Oura K, Tadokoro T, Tani J, Morishita A, Ono M, Himoto T, Masaki T. Predictors of therapeutic response to peginterferon α‑2a and nucleos(t)ide analog combination therapy for HBeAg‑negative chronic hepatitis B: 1‑year follow‑up after treatment. Exp Ther Med 2023; 26:587. [PMID: 38023352 PMCID: PMC10665991 DOI: 10.3892/etm.2023.12286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 10/18/2023] [Indexed: 12/01/2023] Open
Abstract
Chronic hepatitis B (CHB) is a major global health concern. Guidelines for the management of hepatitis B virus (HBV) indicate that the loss of hepatitis B surface antigen (HBsAg) is a key endpoint of interest. The present study aimed to examine long-term changes in HBsAg levels in HBV-DNA-negative, hepatitis B e-antigen (HBeAg)-negative patients treated with peginterferon (Peg-IFN) α-2a and nucleos(t)ide analog (NA), and to examine the conditions that make them susceptible to HBsAg decline. A total of 17 patients with CHB treated with NA and Peg-IFN were observed for 96 weeks (48 weeks of Peg-IFN therapy and 48 weeks of post-treatment follow-up). In this study, responders were defined as those with a 50% or greater decrease in HBsAg levels from baseline at week 96. Beginning at week 16 of Peg-IFN therapy, there was a significant difference in the decrease in HBsAg levels from baseline between the responders and non-responders. In responders, HBsAg levels tended to be >60% lower 16 weeks after Peg-IFN initiation than before initiation. Age at the start of NA use and the duration of NA use before Peg-IFN treatment initiation were significant pretreatment factors associated with HBsAg response. In conclusion, Peg-IFN was revealed to be more effective in HBeAg-negative patients with CHB who started NA at a young age and have been on long-term treatment, particularly if the HBsAg levels decreased to less than 60% of the starting level at week 16 after starting Peg-IFN treatment.
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Affiliation(s)
- Shima Mimura
- Department of Gastroenterology and Neurology, Kagawa University Hospital, Kita, Kagawa 761-0793, Japan
| | - Koji Fujita
- Department of Gastroenterology and Neurology, Kagawa University Hospital, Kita, Kagawa 761-0793, Japan
| | - Kei Takuma
- Department of Gastroenterology and Neurology, Kagawa University Hospital, Kita, Kagawa 761-0793, Japan
| | - Mai Nakahara
- Department of Gastroenterology and Neurology, Kagawa University Hospital, Kita, Kagawa 761-0793, Japan
| | - Kyoko Oura
- Department of Gastroenterology and Neurology, Kagawa University Hospital, Kita, Kagawa 761-0793, Japan
| | - Tomoko Tadokoro
- Department of Gastroenterology and Neurology, Kagawa University Hospital, Kita, Kagawa 761-0793, Japan
| | - Joji Tani
- Department of Gastroenterology and Neurology, Kagawa University Hospital, Kita, Kagawa 761-0793, Japan
| | - Asahiro Morishita
- Department of Gastroenterology and Neurology, Kagawa University Hospital, Kita, Kagawa 761-0793, Japan
| | - Masafumi Ono
- Department of Gastroenterology and Neurology, Kagawa University Hospital, Kita, Kagawa 761-0793, Japan
| | - Takashi Himoto
- Department of Medical Technology, Kagawa Prefectural University of Health Sciences, Takamatsu, Kagawa 761-0123, Japan
| | - Tsutomu Masaki
- Department of Gastroenterology and Neurology, Kagawa University Hospital, Kita, Kagawa 761-0793, Japan
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Grecu LI, Sultana C, Pavel-Tanasa M, Ruta SM, Chivu-Economescu M, Matei L, Ursu RG, Iftimi E, Iancu LS. Non-Invasive Prediction Scores for Hepatitis B Virus- and Hepatitis D Virus-Infected Patients-A Cohort from the North-Eastern Part of Romania. Microorganisms 2023; 11:2895. [PMID: 38138039 PMCID: PMC10745361 DOI: 10.3390/microorganisms11122895] [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: 11/06/2023] [Revised: 11/22/2023] [Accepted: 11/28/2023] [Indexed: 12/24/2023] Open
Abstract
Approximately 62-72 million people are infected worldwide with HDV. Patients with chronic hepatitis D (CHD) have a higher risk of developing cirrhosis or hepatocellular carcinoma (HCC) and an increased mortality rate compared to those with chronic hepatitis B (CHB). The stage of liver fibrosis or the risk of developing HCC can also be estimated by non-invasive scores, which are cost effective, easier to apply, and reproducible. In this study, we aimed to evaluate the predictive value of four non-invasive scores (FIB-4, APRI, AST/ALT ratio, and aMAP) in assessing severe fibrosis/cirrhosis and the presence of HCC in patients with HBV/HDV superinfection, as compared with HBV mono-infection. Our 8-year retrospective analysis revealed that HDV-infected patients had a 2-3 times higher risk of developing cirrhosis and HCC than HBV-mono-infected subjects. High AST and ALT baseline levels qualified as independent predictors for cirrhosis development in both groups. The following fibrosis scores, FIB-4, APRI score, and AAR, were significantly increased when cirrhosis was present at baseline and showed a good prediction for developing cirrhosis in the CHD group. The aMAP score, a risk predictor for HCC, showed significantly higher values in patients with HCC in both groups. Nonetheless, non-invasive scores should always be considered for monitoring patients with CHB and CHD, but only when associated with other diagnosis methods.
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Affiliation(s)
- Laura Iulia Grecu
- Department of Preventive Medicine and Interdisciplinarity, Microbiology Discipline, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (L.I.G.); (R.G.U.); (L.S.I.)
- Department of Emerging Viral Diseases, “Stefan S. Nicolau” Institute of Virology, 030304 Bucharest, Romania;
| | - Camelia Sultana
- Department of Emerging Viral Diseases, “Stefan S. Nicolau” Institute of Virology, 030304 Bucharest, Romania;
- Virology Discipline, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Mariana Pavel-Tanasa
- Department of Immunology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania;
| | - Simona Maria Ruta
- Department of Emerging Viral Diseases, “Stefan S. Nicolau” Institute of Virology, 030304 Bucharest, Romania;
- Virology Discipline, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Mihaela Chivu-Economescu
- Department of Cellular and Molecular Pathology, “Stefan S. Nicolau” Institute of Virology, 030304 Bucharest, Romania; (M.C.-E.)
| | - Lilia Matei
- Department of Cellular and Molecular Pathology, “Stefan S. Nicolau” Institute of Virology, 030304 Bucharest, Romania; (M.C.-E.)
| | - Ramona Gabriela Ursu
- Department of Preventive Medicine and Interdisciplinarity, Microbiology Discipline, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (L.I.G.); (R.G.U.); (L.S.I.)
| | - Elena Iftimi
- Department of Immunology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania;
| | - Luminita Smaranda Iancu
- Department of Preventive Medicine and Interdisciplinarity, Microbiology Discipline, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (L.I.G.); (R.G.U.); (L.S.I.)
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Li YP, Liu CR, Hao M, Lu R, Dang SS. Clinical cure of hepatitis B: Delight and anticipation. Shijie Huaren Xiaohua Zazhi 2023; 31:837-845. [DOI: 10.11569/wcjd.v31.i20.837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 10/05/2023] [Accepted: 10/23/2023] [Indexed: 10/27/2023] Open
Affiliation(s)
- Ya-Ping Li
- Department of Infectious Diseases, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
| | - Chen-Rui Liu
- Department of Infectious Diseases, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
| | - Miao Hao
- Department of Infectious Diseases, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
| | - Rui Lu
- Department of Infectious Diseases, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
| | - Shuang-Suo Dang
- Department of Infectious Diseases, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
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Jia H, Yu G, Yu J, Zhang X, Yang L, Wang B, Zhang J, Bai L, Zhang X, Wang K, Zhao P, Yang D, Zhao Y, Yu Y, Zhang Y, Gu J, Ye C, Cai H, Lu Y, Xiang D, Yu L, Lian J, Hu J, Zhang S, Jin C, Yang Y. Immunomodulatory and Antiviral Therapy Improved Functional Cure Rate in CHB Patients with High HBsAg Level Experienced NA. J Clin Transl Hepatol 2023; 11:1003-1010. [PMID: 37577218 PMCID: PMC10412713 DOI: 10.14218/jcth.2022.00413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 12/16/2022] [Accepted: 01/18/2023] [Indexed: 07/03/2023] Open
Abstract
BACKGROUND AND AIMS A functional cure, or hepatitis B virus (HBV) surface antigen (HBsAg) loss, is difficult to achieve in patients with hepatitis B virus e antigen (HBeAg)-positive chronic hepatitis B. The HBV vaccine and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been reported to help reduce HBsAg levels and promote HBsAg loss. In this prospective randomized trial, we evaluated HBsAg loss in patients receiving pegylated interferon-α2b (PEGIFN-α2b) and tenofovir disoproxil fumarate (TDF), with and without GM-CSF and HBV vaccination. METHODS A total of 287 patients with HBeAg positive chronic hepatitis B and seroconversion after nucleot(s)ide analog treatment were assigned randomly to three treatment groups for 48 weeks, TDF alone (control), PEGIFN-α2b + TDF, and PEGIFN-α2b + TDF + GM-CSF + HBV vaccine. The primary endpoints were the proportions of patients with HBsAg loss and seroconversion at 48 and 72 weeks. RESULTS The cumulative HBsAg loss rates in the control, PEGIFN-α2b + TDF, and PEGIFN-α2b + TDF + GM-CSF + HBV vaccine groups at week 48 were 0.0%, 28.3%, and 41.1%, respectively. The cumulative HBsAg seroconversion rates in these groups at week 48 were 0.0%, 21.7%, and 33.9%, respectively. Multivariate regression analysis showed that GM-CSF use plus HBV vaccination was significantly associated with HBsAg loss (p=0.017) and seroconversion (p=0.030). CONCLUSIONS In patients with HBeAg-positive chronic hepatitis B and seroconversion after nucleot(s)ide analog treatment, immunomodulatory/antiviral treatment regimens effectively improved HBsAg loss, and the regimen including GM-CSF and HBV vaccination was most effective.
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Affiliation(s)
- Hongyu Jia
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Research Units of Infectious disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, Zhejiang, China
- Department of Infectious Diseases,Branch of the First Affiliated Hospital of Zhejiang University School of Medicine, Ningbo, Zhejiang, China
| | - Guodong Yu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Research Units of Infectious disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, Zhejiang, China
| | - Jiong Yu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Research Units of Infectious disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, Zhejiang, China
| | - Xiaoli Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Research Units of Infectious disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, Zhejiang, China
| | - Lisha Yang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Research Units of Infectious disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, Zhejiang, China
| | - Bin Wang
- Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai, China
| | - Jiming Zhang
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Lang Bai
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Xinxin Zhang
- Department of Infectious Disease, Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Kai Wang
- Department of Hepatology, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Ping Zhao
- International Center for Liver Disease Treatment, 302 Hospital Beijing, Beijing, China
| | - Dongliang Yang
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yingren Zhao
- Department of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Yanyan Yu
- Department of Infectious Diseases, Peking University First Hospital, Beijing, China
| | - Yimin Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Research Units of Infectious disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, Zhejiang, China
| | - Jueqing Gu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Research Units of Infectious disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, Zhejiang, China
| | - Chanyuan Ye
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Research Units of Infectious disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, Zhejiang, China
| | - Huan Cai
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Research Units of Infectious disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, Zhejiang, China
| | - Yingfeng Lu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Research Units of Infectious disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, Zhejiang, China
| | - Dairong Xiang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Research Units of Infectious disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, Zhejiang, China
| | - Liang Yu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Research Units of Infectious disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, Zhejiang, China
| | - Jiangshan Lian
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Research Units of Infectious disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, Zhejiang, China
| | - Jianhua Hu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Research Units of Infectious disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, Zhejiang, China
| | - Shanyan Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Research Units of Infectious disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, Zhejiang, China
| | - Ciliang Jin
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Research Units of Infectious disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, Zhejiang, China
| | - Yida Yang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Research Units of Infectious disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, Zhejiang, China
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Cao X, Hu Q, Xu W, Li Q, Zhang J, Chen L, Huang Y, Qi X. Kinetics changes in total cholesterol predict HBeAg seroconversion in chronic hepatitis B patients treated with pegylated interferon-alfa. J Viral Hepat 2023; 30:310-318. [PMID: 36529685 DOI: 10.1111/jvh.13787] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 11/24/2022] [Accepted: 12/10/2022] [Indexed: 01/07/2023]
Abstract
There is no satisfactory standard for predicting HBeAg seroconversion during Pegylated interferon alpha (PegIFNα) treatment. Studies have shown that IFNα therapy in chronic hepatitis C patients could alter serum lipid profiles. However, there have been no studies on lipid changes that predict the outcome of PegIFNα monotherapy in treated-naive chronic hepatitis B (CHB) patients. This retrospective study included 130 treated-naive HBeAg-positive CHB patients receiving PegIFNα monotherapy. The relationship between serum lipid changes and HBeAg seroconversion was analysed. The TC-ALT-HBsAg-HBeAg-Genotype-Age (CASEGA) model was established to predict HBeAg seroconversion after PegIFN-α monotherapy. Among 130 patients, 33 achieved HBeAg seroconversion (SR) and 97 did not achieve HBeAg seroconversion (NR). The decrease in serum total cholesterol (TC) in the NR group was significantly higher than in the SR group at Week 24 (-9.59% vs. -0.31%, p < 0.001). Multivariate logistic regression analysis showed that the change in TC at Week 24 (odds ratio = 1.065, p = 0.009) was an independent predictor of HBeAg seroconversion. The area under the receiver operating characteristic curve for the CASEGA model was 0.883. The model score at the maximum Youden index was 90, and the specificity, sensitivity, positive predictive value and negative predictive value were 0.727, 0.794, 0.546 and 0.895, respectively. The HBeAg seroconversion rate at Week 72 in patients with scores >90 was significantly higher than that in patients with scores <90 (54.55% vs. 10.47%, p < 0.001). This study indicated that the change in the TC level at 24 weeks in CHB patients treated with PegIFNα was associated with HBeAg seroconversion. The CASEGA prediction model based on the TC change rate of 24 weeks has good predictive efficiency for HBeAg seroconversion.
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Affiliation(s)
- Xiongyue Cao
- Department of Hepatology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Qiankun Hu
- Department of Hepatology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Wei Xu
- Department of Hepatology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Qiang Li
- Department of Hepatology, Shanghai Public Health Clinical Center, Fudan University, 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 Hepatology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Yuxian Huang
- Department of Hepatology, 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
| | - Xun Qi
- Department of Hepatology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
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Wang WX, Jia R, Jin XY, Li X, Zhou SN, Zhang XN, Zhou CB, Wang FS, Fu J. Serum cytokine change profile associated with HBsAg loss during combination therapy with PEG-IFN-α in NAs-suppressed chronic hepatitis B patients. Front Immunol 2023; 14:1121778. [PMID: 36756119 PMCID: PMC9899895 DOI: 10.3389/fimmu.2023.1121778] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Accepted: 01/09/2023] [Indexed: 01/24/2023] Open
Abstract
Objective The aim of this study was to explore the profile of cytokine changes during the combination therapy with pegylated interferon alpha (PEG-IFN-α) and its relationship with HBsAg loss in nucleos(t)ide analogs (NAs)-suppressed chronic hepatitis B patients. Methods Seventy-six patients with chronic hepatitis B with HBsAg less than 1,500 IU/ml and HBV DNA negative after receiving ≥ 1-year NAs therapy were enrolled. Eighteen patients continued to take NAs monotherapy (the NAs group), and 58 patients received combination therapy with NAs and PEG-IFN-α (the Add-on group). The levels of IFNG, IL1B, IL1RN, IL2, IL4, IL6, IL10, IL12A, IL17A, CCL2, CCL3, CCL5, CXCL8, CXCL10, TNF, and CSF2 in peripheral blood during treatment were detected. Results At week 48, 0.00% (0/18) in the NAs group and 25.86% (15/58) in the Add-on group achieved HBsAg loss. During 48 weeks of combined treatment, there was a transitory increase in the levels of ALT, IL1RN, IL2, and CCL2. Compared to the NAs group, CXCL8 and CXCL10 in the Add-on group remain higher after rising, yet CCL3 showed a continuously increasing trend. Mild and early increases in IL1B, CCL3, IL17A, IL2, IL4, IL6, and CXCL8 were associated with HBsAg loss or decrease >1 log, while sustained high levels of CCL5 and CXCL10 were associated with poor responses to Add-on therapy at week 48. Conclusions The serum cytokine change profile is closely related to the response to the combination therapy with PEG-IFN-α and NAs, and may help to reveal the mechanism of functional cure and discover new immunological predictors and new therapeutic targets.
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Affiliation(s)
- Wen-Xin Wang
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Peking University 302 Clinical Medical School, National Clinical Research Center for Infectious Diseases, Beijing, China
| | - Rui Jia
- Department of Gastroenterology, The 985th Hospital of Joint Logistic Support Force of Chinese PLA, Taiyuan, China
| | - Xue-Yuan Jin
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Peking University 302 Clinical Medical School, National Clinical Research Center for Infectious Diseases, Beijing, China
| | - Xiaoyan Li
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Peking University 302 Clinical Medical School, National Clinical Research Center for Infectious Diseases, Beijing, China,Medical School of Chinese PLA, Beijing, China
| | - Shuang-Nan Zhou
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Peking University 302 Clinical Medical School, National Clinical Research Center for Infectious Diseases, Beijing, China
| | - Xiao-Ning Zhang
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Peking University 302 Clinical Medical School, National Clinical Research Center for Infectious Diseases, Beijing, China
| | - Chun-Bao Zhou
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Peking University 302 Clinical Medical School, National Clinical Research Center for Infectious Diseases, Beijing, China
| | - Fu-Sheng Wang
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Peking University 302 Clinical Medical School, National Clinical Research Center for Infectious Diseases, Beijing, China,Medical School of Chinese PLA, Beijing, China,*Correspondence: Junliang Fu, ; Fu-Sheng Wang,
| | - Junliang Fu
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Peking University 302 Clinical Medical School, National Clinical Research Center for Infectious Diseases, Beijing, China,Medical School of Chinese PLA, Beijing, China,*Correspondence: Junliang Fu, ; Fu-Sheng Wang,
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Wu F, Wang Y, Cui D, Tian Y, Lu R, Liu C, Li M, Li Y, Gao N, Jiang Z, Li X, Zhai S, Zhang X, Jia X, Dang S. Short-Term Peg-IFN α-2b Re-Treatment Induced a High Functional Cure Rate in Patients with HBsAg Recurrence after Stopping Peg-IFN α-Based Regimens. J Clin Med 2023; 12:361. [PMID: 36615161 PMCID: PMC9821570 DOI: 10.3390/jcm12010361] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Revised: 12/22/2022] [Accepted: 12/23/2022] [Indexed: 01/04/2023] Open
Abstract
Little is known about the treatment of patients with hepatitis B surface antigen (HBsAg) recurrence after being clinically cured by peginterferon alpha(peg-IFN-α)-based regimens. This study aimed to investigate the efficacy and safety of peg-IFNα-2b in re-treating patients with HBsAg recurrence after stopping peg-IFN α-based regimens. In this two-center, prospective observational study, 33 patients with HBsAg recurrence after stopping peg-IFN α-based regimens were enrolled and re-treated with an individualized course of peg-IFN α-2b. The hepatitis B virus (HBV) vaccine could be injected immediately after HBsAg clearance, according to patients’ willingness. All patients were monitored and followed-up for 48 weeks after peg-IFN α-2b re-treatment stop. The primary endpoint was HBsAg clearance at the end of follow-up. At baseline, all patients had HBsAg levels of <10 IU/mL and undetectable HBV DNA, with the median HBsAg level of 1.66 (0.56−2.87) IU/mL. After a median of 24 (24−30) weeks of peg-IFN α-2b re-treatment, 87.9% (29/33) of the patients achieved HBsAg clearance again and 66.7% (22/33) of the patients achieved HBsAg seroconversion. At the end of follow-up, the HBsAg clearance and HBsAg seroconversion rates decreased to 78.8% (26/33) and 51.5% (17/33), respectively. Furthermore, 88.9% (16/18) of the patients with HBsAg clearance benefited from receiving the HBV vaccine therapy. Generally, both peg-IFN α-2b and HBV vaccine therapy were well tolerated. A high functional cure rate can be achieved by a short-course of peg-IFN α-2b re-treatment in patients with HBsAg recurrence after stopping peg-IFN α-based regimens. Furthermore, injecting HBV vaccine is beneficial after HBsAg clearance.
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Affiliation(s)
- Fengping Wu
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Yikai Wang
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Dandan Cui
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Yan Tian
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Rui Lu
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Chenrui Liu
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Mei Li
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Yaping Li
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Ning Gao
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Zicheng Jiang
- Department of Infectious Diseases, Ankang Central Hospital, Ankang 725000, China
| | - Xuemei Li
- Department of Infectious Diseases, Ankang Central Hospital, Ankang 725000, China
| | - Song Zhai
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Xin Zhang
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Xiaoli Jia
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Shuangsuo Dang
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
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Li H, Liang S, Liu L, Zhou D, Liu Y, Zhang Y, Chen X, Zhang J, Cao Z. Clinical cure rate of inactive HBsAg carriers with HBsAg <200 IU/ml treated with pegylated interferon. Front Immunol 2022; 13:1091786. [PMID: 36618361 PMCID: PMC9822570 DOI: 10.3389/fimmu.2022.1091786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Accepted: 12/06/2022] [Indexed: 12/24/2022] Open
Abstract
Purpose HBsAg clearance represents clinical cure for patients with hepatitis B, but remains difficult to obtain for most HBV-infected patients. Recent studies have shown that inactive HBsAg carriers treated with pegylated interferon can achieve higher clinical cure rates, which may imply that the lower the baseline HBsAg quantification, the higher HBsAg clearance rate. Therefore, this study further investigated the HBsAg clearance rate in inactive HBsAg carriers with low level of HBsAg (<200 IU/ml) treated with pegylated interferon. Methods This is a prospective cohort study. Inactive HBsAg carriers with HBsAg<200 IU/ml were divided into treatment and control groups. Pegylated interferon was administered to the patients in therapeutic group for 96 weeks. The patients in control group underwent 96 weeks of observation without any anti-viral treatment. All patients were tested for HBsAg, anti-HBs, HBV DNA, liver function, blood count, thyroid function, thyroid antibodies and autoantibodies at baseline, week 12, 24, 36, 48, 60, 72, 84 and 96. Controlled attenuation parameter (CAP) and liver stiffness measure (LSM) were evaluated at baseline and week 96. Patients were classified into no steatosis, mild steatosis, moderate steatosis and severe steatosis according to the value of CAP. Results A total of 174 inactive HBsAg carriers with HBsAg<200IU/ml were enrolled, including 84 in the treatment group and 90 in the control group. In the treatment group, HBsAg clearance rate was 30.77% (24/78) at week 48, and increased to 57.69% (45/78) at week 96. HBsAg clearance occurred in 2 patients with a clearance rate of 2.27% (2/88) in control group, The HBsAg clearance rate of the treatment group was significantly higher than that of the control group (P<0.001). HBsAg clearance was significantly higher in patients with moderate steatosis than in those without steatosis (74.07% vs. 48.15%, p=0.008) at week 96. Conclusion High HBsAg clearance rate could be obtained for inactive HBsAg carriers with HBsAg< 200 IU/ml treated with peginterferons. Inactive HBsAg carriers with moderate hepatic steatosis are more sensitive for the treatment.
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Affiliation(s)
- Hong Li
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Shan Liang
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Lili Liu
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Daqiong Zhou
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Yali Liu
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Yang Zhang
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Xinyue Chen
- The First Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Jing Zhang
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China,*Correspondence: Zhenhuan Cao, ; Jing Zhang,
| | - Zhenhuan Cao
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China,*Correspondence: Zhenhuan Cao, ; Jing Zhang,
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Zhang W, Xing M, Sun W, Chen J, Xie N, Cai Y, Wang Y, Li N, Jiang Y, Zhang F, Wang Y, Zeng Q, Ji Y, Xu C, Jiang C, Song J, Li G. Early clinical efficacy of pegylated interferon treatment in patients with different phases of chronic HBV infection: A real-world analysis. J Viral Hepat 2022; 30:427-436. [PMID: 36562258 DOI: 10.1111/jvh.13792] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 12/12/2022] [Accepted: 12/14/2022] [Indexed: 12/24/2022]
Abstract
Although there are therapeutic advantages for hepatitis B virus (HBV) withpegylated interferon alpha (peg-IFNα) treatment compared with nucleos(t)ide analog (NAs) therapy, the effect difference in infected population at different phases has not been well established. We studied the clinical efficacy of peg-IFNα in two populations with HBV infection, including inactive HBsAg carrier (IHC) and chronic hepatitis B (CHB). A total of 328 HBV-infected patients were included in this real-world analysis. Patients were divided into two groups according to the infected stages. Peg-IFNα monotherapy or combination therapy with NAs were used in IHCs, and peg-IFNα added-on NAs therapy was applied to patients with CHB. The primary efficacy endpoint was HBsAg loss at Week 24. Results: The Kaplan-Meier cumulative rates of HBsAg loss were 39.50% (n = 47/119) in IHC group and 28.71% (n = 60/209) in CHB group at Week 24 (p < .05). After Propensity Score Matching (PSM), the HBsAg loss rates were 36.84% (n = 35/95) and 32.63% (n = 31/95), respectively (p > .05). Patients with baseline HBsAg level < 100 IU/ml achieved higher rates of HBsAg clearance in IHC and CHB group (before PSM: 47.44% vs. 42.86%, after PSM: 49.12% vs. 45.83%, all p values > .05). Baseline HBsAg level and its level decline from baseline to Week 12 can be as the predictors for HBsAg loss at Week 24 in both groups. Hence, the efficacy of HBsAg clearance was broadly similar between IHCs and NA-treated CHB patients during the early peg-IFNα therapy. A significant downward trend of HBsAg level was observed in both groups during peg-IFNα therapy.
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Affiliation(s)
- Wencong Zhang
- Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Mingyou Xing
- Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wenjin Sun
- Department of Infectious Diseases, Ezhou Central Hospital, Ezhou, China
| | - Jia Chen
- Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Nana Xie
- Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yuan Cai
- Department of Liver Diseases, State Key Discipline of Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Diseases, Shenzhen, China
| | - Ying Wang
- Department of Liver Diseases, State Key Discipline of Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Diseases, Shenzhen, China
| | - Niuniu Li
- Department of Liver Diseases, State Key Discipline of Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Diseases, Shenzhen, China
| | - Yujin Jiang
- Department of Liver Diseases, State Key Discipline of Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Diseases, Shenzhen, China
| | - Fan Zhang
- Department of Liver Diseases, State Key Discipline of Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Diseases, Shenzhen, China
| | - Yanfeng Wang
- Department of Liver Diseases, State Key Discipline of Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Diseases, Shenzhen, China
| | - Qingjin Zeng
- Department of Liver Diseases, State Key Discipline of Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Diseases, Shenzhen, China
| | - Yanhua Ji
- Department of Liver Diseases, State Key Discipline of Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Diseases, Shenzhen, China
| | - Cheng Xu
- Department of Liver Diseases, State Key Discipline of Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Diseases, Shenzhen, China
| | - Chunmei Jiang
- Department of Infectious Diseases, The People's Hospital of Longhua, Shenzhen, China
| | - Jianxin Song
- Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Guojun Li
- Department of Liver Diseases, State Key Discipline of Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Diseases, Shenzhen, China
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Peng MJ, Guo XQ, Zhang WL, Chen J, Kang W, Yang XF, Guo Y, Zhang Y. Effect of pegylated interferon-α2b add-on therapy on renal function in chronic hepatitis B patients: A real-world experience. Front Microbiol 2022; 13:980250. [PMID: 36329842 PMCID: PMC9622795 DOI: 10.3389/fmicb.2022.980250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 10/03/2022] [Indexed: 01/03/2025] Open
Abstract
BACKGROUND AND AIM Controversy remains as to pegylated interferon-α (PEG-IFNα) antiviral therapy to renal function in chronic hepatitis B (CHB) patients. The aim of this study was to evaluate the influence of PEG-IFNα2b (Y shape, 40 kD) add-on treatment for renal function in CHB patients who received entecavir therapy. METHODS This was a retrospective observational study to investigate factors related to renal function in 114 CHB patients who received PEG-IFNα2b add-on therapy to entecavir for 48 weeks. Changes of blood urea nitrogen (BUN), serum creatinine (sCr), and estimated glomerular filtration rate (eGFR), which was calculated with both Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease (MDRD) formulas, were analyzed by one-way analysis of variance. A linear mixed effects model for repeated measures was used to assess the correlation between baseline information and eGFR changes at 24 and 48 weeks of therapy. The model considered the baseline age, gender, body weight, viral load, hepatitis B surface antigen, BUN, sCr, and treatment strategy as fixed effects and incorporated random effects for individual subjects. RESULTS BUN and sCr was decreased, while eGFR was increased at 12 weeks of therapy. Only eGFR maintained at 24 and 48 weeks of therapy. Patients with female gender, age ≥ 40 years, and baseline HBsAg level < 250 IU/mL showed significant improvement of renal function with PEG-IFNα2b add-on therapy. The linear mixed effects model revealed that female gender, baseline sCr, and PEG-IFNα2b add-on were significant positive predictors for eGFR elevation at 24 and 48 weeks of therapy. CONCLUSION In real-world experience, PEG-IFNα2b add-on therapy might be associated with increased eGFR in CHB patients.
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Affiliation(s)
- Mei-Juan Peng
- Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi’an, China
| | - Xiao-Qing Guo
- Department of Hepatology, The Third People’s Hospital of Taiyuan, Taiyuan, China
| | - Wei-Lu Zhang
- Department of Epidemiology, School of Public Health, Fourth Military Medical University, Xi’an, China
| | - Jing Chen
- Xiamen Amoytop Biotech Co., Ltd., Xiamen, China
| | - Wen Kang
- Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi’an, China
| | - Xiao-Fei Yang
- Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi’an, China
| | - Ying Guo
- Department of Hepatology, The Third People’s Hospital of Taiyuan, Taiyuan, China
| | - Ye Zhang
- Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi’an, China
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Yang X, Zhang K, Xu Q, Shu X, Mo Z, Xie D, Gao Z, Deng H. Interferon add-on therapy increased clinical cure significantly for interferon-experienced chronic hepatitis B patients with low HBsAg. Front Immunol 2022; 13:997608. [PMID: 36148219 PMCID: PMC9485616 DOI: 10.3389/fimmu.2022.997608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Accepted: 08/15/2022] [Indexed: 11/15/2022] Open
Abstract
Currently, interferon add-on therapy brings hope for clinical cure of chronic hepatitis B patients with low HBsAg. However, in clinical practice patients with poor responses to their first interferon therapy were often switched to nucleos(t)ide analog therapy and then labeled as unsuitable patients for interferon therapy. Even if their HBsAg levels dropped to a low level, they were reluctant or not recommended to take interferon again, which caused them to miss out on interferon add-on therapy and clinical cure. Therefore, it is urgent to elucidate the effectiveness of interferon add-on therapy to get clinical cure for these interferon-experienced patients with low HBsAg. The purpose of this study was to investigate whether interferon-experienced patients could achieve the same HBsAg clearance and HBsAg seroconversion rates as interferon-naive patients. Also, the associated factor of HBsAg clearance and seroconversion were aimed to be clarified. 292 patients, including 85 interferon-experienced patients, were enrolled with HBsAg< 1500 IU/ml, HBeAg negative and HBV-DNA negative. And then, peg-interferon α-2b add-on therapy was performed. The results showed that the week 48 HBsAg clearance and seroconversion rates of all patients were 29.8% and 22.0%. There was no statistically significant difference between interferon-experienced and interferon-naive patients in week 48 HBsAg clearance and seroconversion rates, suggesting satisfactory clinical cure of the interferon add-on therapy for interferon-experienced patients. The age, baseline HBsAg, and week 12 HBsAg were negative correlated factors for week 48 HBsAg clearance and seroconversion. Furthermore, the age, baseline HBsAg and week 12 HBsAg for predicting the week 48 HBsAg clearance were cut off at 40.5 years, at 152.0 IU/ml and at 34.99 IU/ml, and for predicting seroconversion were cut off at 40.5 years, at 181.9 IU/ml and at 34.99 IU/ml, correspondingly. Significantly, interferon-experienced patients with low HBsAg were suggested with interferon add-on therapy to achieve clinical cure as soon as possible. This research provided evidences and cut-offs for the interferon add-on therapy against chronic hepatitis B.
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Affiliation(s)
- Xiaoan Yang
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Ka Zhang
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Qihuan Xu
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xin Shu
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhishuo Mo
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Dongying Xie
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhiliang Gao
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- *Correspondence: Zhiliang Gao, ; Hong Deng,
| | - Hong Deng
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- *Correspondence: Zhiliang Gao, ; Hong Deng,
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Chu JH, Huang Y, Xie DY, Deng H, Wei J, Guan YJ, Li GJ, Zeng YL, Yang JH, Chen XY, Shang J, Li JB, Gao N, Gao ZL. Real-world study on HBsAg loss of combination therapy in HBeAg-negative chronic hepatitis B patients. J Viral Hepat 2022; 29:765-776. [PMID: 35718996 DOI: 10.1111/jvh.13722] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 04/11/2022] [Accepted: 05/21/2022] [Indexed: 12/22/2022]
Abstract
Combination therapy with pegylated interferon (PEG-IFN) and nucleos(t)ide analogues (NAs) can enhance hepatitis B surface antigen (HBsAg) clearance. However, the specific treatment strategy and the patients who would benefit the most are unclear. Therefore, we assessed the HBsAg loss rate of add-on PEG-IFN and explored the factors associated with HBsAg loss in chronic hepatitis B (CHB) patients. This was a real-world cohort study of adults with CHB. Hepatitis B e antigen (HBeAg)-negative NAs-treated patients with baseline HBsAg ≤1500 IU/ml and HBV DNA < the lower limit of detection, or 100 IU/ml, received 48 weeks of add-on PEG-IFN. The primary outcome of the study was the rate of HBsAg loss at 48 weeks of combination treatment. Using multivariable logistic regression analysis, we determined factors associated with HBsAg loss. HBsAg loss in 2579 patients (mean age: 41.2 years; 80.9% male) was 36.7% (947 patients) at 48 weeks. HBsAg loss was highest in patients from south-central and southwestern China (40.0%). Factors independently associated with HBsAg loss included: increasing age (odds ratio = 0.961); being male (0.543); baseline HBsAg level (0.216); HBsAg decrease at 12 weeks (between 0.5 and 1.0 log10 IU/ml [2.405] and >1.0 log10 IU/ml [7.370]); alanine aminotransferase (ALT) increase at 12 weeks (1.365); haemoglobin (HGB) decrease at 12 weeks (1.558). There was no difference in the primary outcomes associated with the combination regimen. In conclusion, HBsAg loss by combination therapy was higher in patients from southern China than those from the north. An increased chance of HBsAg loss was associated with baseline characteristics and dynamic changes in clinical indicators.
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Affiliation(s)
- Jun-Hao Chu
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Yan Huang
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Dong-Ying Xie
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.,Guandong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.,Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, Guangzhou, Guangdong, China
| | - Hong Deng
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.,Guandong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.,Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, Guangzhou, Guangdong, China
| | - Jia Wei
- Department of Gastroenterology, the Second People's Hospital Yunnan Province, Kunming, Yunnan, China
| | - Yu-Juan Guan
- Department of Hepatology, Guangzhou Eighth People's Hospital, Guangzhou, Guangdong, China
| | - Guo-Jun Li
- Department of Hepatology, Shenzhen Third People's Hospital, Shenzhen, Guangdong, China
| | - Yi-Lan Zeng
- Department of Hepatology, Chengdu Public Health Clinical Medical Center, Chengdu, Sichuan, China
| | - Jia-Hong Yang
- Department of Infectious Diseases, Deyang People's Hospital, Deyang, Sichuan, China
| | - Xin-Yue Chen
- Department of Hepatology, Beijing You'an Hospital, Capital Medical University, Beijing, China
| | - Jia Shang
- Department of Infectious Diseases, Henan Provincial People's Hospital, Zhengzhou, Henan, China
| | - Jia-Bin Li
- Department of Infectious Diseases, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Na Gao
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Zhi-Liang Gao
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.,Guandong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.,Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, Guangzhou, Guangdong, China
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Feng B, Zheng JR. Importance of quantitative HBsAg detection in whole course management of patients with chronic hepatitis B. Shijie Huaren Xiaohua Zazhi 2022; 30:655-660. [DOI: 10.11569/wcjd.v30.i15.655] [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: 02/07/2023] Open
Abstract
HBsAg is the earliest known serum marker for hepatitis B virus (HBV). It plays an important role in the pathogenesis, diagnosis, and prevention of chronic hepatitis B (CHB). In the era of antiviral therapy, the concept of functional cure is put forward. HBsAg, as an old marker of HBV infection, has been found to have more and more new applications in the management of CHB patients. Positive HBsAg is taken as the indication of antiviral treatment in special CHB patients. The level of HBsAg is conducive to the selection of treatment regimens, and the dynamics of HBsAg is conducive to the adjustment of treatment scheme. HBsAg level and its kinetics can predict the therapeutic effect and disease outcome, and guide drug withdrawal. Further research is needed on the sensitivity of HBsAg, its impact on long-term outcomes, and its value in functional cure and complete cure.
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Affiliation(s)
- Bo Feng
- Department of Hepatology, Peking University People's Hospital, Peking University Hepatology Institute, Beijing 100044, China
| | - Jia-Rui Zheng
- Department of Hepatology, Peking University People's Hospital, Peking University Hepatology Institute, Beijing 100044, China
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Wang WX, Jia R, Gao YY, Liu JY, Luan JQ, Qiao F, Liu LM, Zhang XN, Wang FS, Fu J. Quantitative anti-HBc combined with quantitative HBsAg can predict HBsAg clearance in sequential combination therapy with PEG-IFN-α in NA-suppressed chronic hepatitis B patients. Front Immunol 2022; 13:894410. [PMID: 35958609 PMCID: PMC9360425 DOI: 10.3389/fimmu.2022.894410] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 06/29/2022] [Indexed: 11/13/2022] Open
Abstract
Background and aimsPrecise predictors are lacking for hepatitis B surface antigen (HBsAg) clearance under the combination therapy of nucleos(t)ide analogs (NA) and pegylated interferon-alpha (PEG-IFN-α) in patients with chronic hepatitis B (CHB). This study aimed to determine the quantitative anti-hepatitis B core antibody (qAnti-HBc) and quantitative hepatitis B core-related antigen (qHBcrAg) as predictors for HBsAg clearance in NA-suppressed patients with CHB receiving PEG-IFN-α add-on therapy.MethodsSeventy-four CHB patients who achieved HBV DNA suppression (HBV DNA < 20 IU/ml) and quantitative HBsAg (qHBsAg) < 1,500 IU/ml after ≥1 year of NA treatment were enrolled. Fifteen patients continued on NA monotherapy, while 59 patients received PEG-IFN-α add-on therapy. Serum qAnti-HBc and qHBcrAg levels were detected every 12 or 24 weeks for add-on and NA-alone groups, respectively.ResultsSerum qAnti-HBc but not qHBcrAg levels at baseline were negatively correlated with the duration of prior NA therapy. After 48-week treatment, both qAnti-HBc and qHBcrAg levels declined further, and 17/59 (28.81%) and 0/15 (0%) achieved HBsAg clearance in add-on and NA groups, respectively. In the add-on group, the rate of HBsAg clearance was significantly higher in patients with baseline qAnti-HBc < 0.1 IU/ml (52.63%). Logistic regression analysis identified baseline qAnti-HBc but not qHBcrAg, which was an independent predictor for HBsAg loss. Receiver operating characteristic curve analysis showed that the combination of qAnti-HBc and qHBsAg had a better predictive value for HBsAg clearance.ConclusionsA combination of qHBsAg and baseline qAnti-HBc levels may be a better prediction strategy for HBsAg clearance in NA-suppressed CHB patients receiving PEG-IFN-α add-on therapy.
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Affiliation(s)
- Wen-Xin Wang
- Peking University 302 Clinical Medical School, Beijing, China
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
- Medical School of Chinese People's Liberation Army (PLA), Beijing, China
| | - Rui Jia
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
- Medical School of Chinese People's Liberation Army (PLA), Beijing, China
| | - Ying-Ying Gao
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
| | - Jia-Ye Liu
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
| | - Jun-Qing Luan
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
| | - Fei Qiao
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
| | - Li-Min Liu
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
| | - Xiao-Ning Zhang
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
| | - Fu-Sheng Wang
- Peking University 302 Clinical Medical School, Beijing, China
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
- Medical School of Chinese People's Liberation Army (PLA), Beijing, China
- *Correspondence: Junliang Fu, ; Fu-Sheng Wang,
| | - Junliang Fu
- Peking University 302 Clinical Medical School, Beijing, China
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
- Medical School of Chinese People's Liberation Army (PLA), Beijing, China
- *Correspondence: Junliang Fu, ; Fu-Sheng Wang,
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Mao QG, Liang HQ, Yin YL, Tang JM, Yang JE, Wu CC, Chen Y, Zhang MY, Liu YY, Zheng XT, Zhuang LY, Chen SD. Comparison of Interferon-α-based therapy and nucleos(t)ide analogs in preventing adverse outcomes in patients with chronic hepatitis B. Clin Res Hepatol Gastroenterol 2022; 46:101758. [PMID: 34303003 DOI: 10.1016/j.clinre.2021.101758] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Revised: 06/17/2021] [Accepted: 06/21/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND Whether interferon (IFN)-α therapy is better than nucleos(t)ide analogs (NAs) in the prevention of adverse outcomes, including hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) is still uncertain or controversial. This study aimed to compare the cumulative incidence of adverse outcomes in patients with CHB on IFN-α- and NA-based therapies. METHODS This was a retrospective study of patients with CHB on antivirals. Patients treated with IFN-α (IFN-α or peginterferon-α) with or without NAs were defined as the IFN-α group, and those only receiving NAs were defined as the NAs group. Propensity score matching (PSM) was used to minimize baseline bias. Cox regression models were performed to select possible factors related to adverse outcomes development. RESULTS All 1247 patients were divided into the IFN-α (n = 877) and NAs (n = 370) groups. 26patients (20 and 6 in the NAs and IFN-α groups) developed adverse outcomes (decompensated cirrhosis, liver failure, HCC, liver transplantation and deaths) during a median follow-up of 5.2 years. The cumulative adverse outcomes occurrence at 10 years was significantly lower in the IFN-α group than in the NAs group in all (1.1% vs. 11.9%, P <0.001) and treatment-naïve (1.1% vs. 12.4%, P <0.001) patients. Similar trends were observed after PSM and differentiation of cirrhosis. Multivariate analysis before and after PSM showed that IFN-α-based treatment was independently associated with a lower adverse outcomes incidence (before/after PSM: P = 0.001/P = 0.002). HCC risk stratification analyses revealed that the superiority of IFN-α in preventing HCC was more significant in patients with high-risk HCC. CONCLUSIONS IFN-α-based therapy was superior to NAs in preventing adverse outcomes in patients with CHB regardless of cirrhosis, and in reducing HCC in those with a high risk of HCC.
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Affiliation(s)
- Qian-Guo Mao
- Xiamen Hospital of Traditional Chinese Medicine, Xiamen, 361009, China.
| | - Hui-Qing Liang
- Xiamen Hospital of Traditional Chinese Medicine, Xiamen, 361009, China.
| | - Ya-Lin Yin
- School of Life Sciences, Xiamen University, Xiamen, 361102, China
| | - Jin-Mo Tang
- Xiamen Hospital of Traditional Chinese Medicine, Xiamen, 361009, China
| | - Jia-En Yang
- Xiamen Hospital of Traditional Chinese Medicine, Xiamen, 361009, China
| | - Chun-Cheng Wu
- Xiamen Hospital of Traditional Chinese Medicine, Xiamen, 361009, China
| | - Yue Chen
- Xiamen Hospital of Traditional Chinese Medicine, Xiamen, 361009, China
| | - Man-Ying Zhang
- Xiamen Hospital of Traditional Chinese Medicine, Xiamen, 361009, China
| | - Yao-Yu Liu
- College of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 351012, China
| | - Xiao-Ting Zheng
- College of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 351012, China
| | - Lin-Yi Zhuang
- College of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 351012, China
| | - Shao-Dong Chen
- School of Medicine, Xiamen University, Xiamen, 361102, China.
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Zhu S, Wu L, Mei Y, Liu Z, Lin L, Yuan J, Li J, Li X, Peng L. Prospective, multicentre, randomised controlled trial comparing the seroclearance of HBsAg between combination therapy of peg-interferon alpha and tenofovir with tenofovir monotherapy in nucleos(t)ide analogue-experienced patients with HBV-related liver fibrosis: a study protocol. BMJ Open 2021; 11:e049104. [PMID: 34697111 PMCID: PMC8547364 DOI: 10.1136/bmjopen-2021-049104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
INTRODUCTION Combination antiviral therapy of nucleos(t)ide analogue (NA) and pegylated interferon alpha (peg-IFN alpha) decrease hepatitis B virus (HBV) surface antigen (HBsAg) levels to achieve functional cure and improve long-term prognosis in chronic hepatitis B patients. However, for hepatitis B-related liver fibrosis, studies on combination of these two medicines are limited. This study was designed to compare the efficacy between peg-IFN alpha combined with tenofovir (TDF) and TDF monotherapy for the clearance of HBsAg in NA-experienced patients with HBV-related liver fibrosis. METHODS AND ANALYSIS This study was designed to be a prospective, multicentre, open, randomised controlled study. A total of 272 patients with HBV-related liver fibrosis will be randomised into the combination therapy group or the monotherapy group at a 1:1 ratio. Participants in the combination group will receive subcutaneous injections of peg-IFN alpha 180 µg per week for 48 weeks combined with oral TDF 300 mg daily. Participants in the monotherapy group will receive 300 mg oral TDF daily alone. All participants will undergo long-term treatment with TDF and will be followed up at the outpatient department for 144 weeks after randomisation. Clinical symptoms, laboratory tests and examination indicators will be collected at each follow-up time point, and adverse events will be recorded. The primary endpoint is serological clearance rate of HBsAg at 48 weeks. ETHICS AND DISSEMINATION The ethics committee of the Third Affiliated Hospital at Sun Yat-sen University approved this study (Approval Number: (2020)02-183-01). The results of the study will be presented at relevant meetings and published in an appropriate journal after the completion of the trial and the analysis of the data. TRIAL REGISTRATION NUMBER NCT04640129.
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Affiliation(s)
- Shu Zhu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Lina Wu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Yongyu Mei
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Zhihua Liu
- Department of Infectious Disease, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Luping Lin
- Department of Traditional Chinese Medicine, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Jing Yuan
- Department of Infectious Diseases, The Third People's Hospital Of Shenzhen, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, Guangdong, China
| | - Jianguo Li
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Xuejun Li
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Liang Peng
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
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Wu F, Lu R, Liu Y, Wang Y, Tian Y, Li Y, Li M, Wang W, Zhang X, Jia X, Dang S. Efficacy and safety of peginterferon alpha monotherapy in Chinese inactive chronic hepatitis B virus carriers. Liver Int 2021; 41:2032-2045. [PMID: 33896094 DOI: 10.1111/liv.14897] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2020] [Revised: 02/27/2021] [Accepted: 03/31/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS The effectiveness and safety of peginterferon alpha (peg-IFN-α) monotherapy in inactive hepatitis B virus (HBV) carriers (IHCs) have not been fully evaluated. METHODS This observational study prospectively enrolled 298 IHCs in China from 2015 to 2019. Participants were given the right to choose to either receive peg-IFN-α monotherapy (treatment group, n = 142) or be monitored without treatment (control group, n = 156) according to their wishes. The scheduled treatment duration was 48 weeks. All participants were followed up to 72 weeks. The main efficacy endpoint was hepatitis B surface antigen (HBsAg) clearance at 72 weeks. RESULTS Baseline characteristics were similar between both groups. At 72 weeks, intention-to-treat analysis showed that the rates of HBsAg clearance and seroconversion of the treatment group were 47.9% (68/142) and 36.6% (52/142), respectively, which were significantly higher than the HBsAg clearance rate of 1.9% (3/156) and the seroconversion rate of 0.6% (1/156) in the control group (both P < .001). Baseline HBV DNA < 20 IU/mL, lower HBsAg levels at baseline, 12 and 24 weeks, alanine aminotransferase elevation at 12 weeks, and greater HBsAg reduction from baseline to 12 and 24 weeks were independent predictors of HBsAg clearance. Generally, the therapy was well tolerated. Only five participants discontinued therapy as a result of peg-IFNα-related adverse events. CONCLUSIONS Peg-IFN-α monotherapy results in high rates of HBsAg clearance and seroconversion and the treatment is safe for IHCs.
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Affiliation(s)
- Fengping Wu
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Rui Lu
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yixin Liu
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yikai Wang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yan Tian
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yaping Li
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Mei Li
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Wenjun Wang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xin Zhang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xiaoli Jia
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Shuangsuo Dang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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Lu H, Yi W, Sun F, Zeng Z, Zhang L, Li M, Xie Y. Comprehensive investigation of HBV-related hepatocellular carcinoma and choice of anti-HBV therapy. BIOSAFETY AND HEALTH 2021. [DOI: 10.1016/j.bsheal.2021.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Chen J, Qi M, Fan XG, Hu XW, Liao CJ, Long LY, Zhao XT, Tan M, Li HF, Chen RC, Huang ZB, Huang Y. Efficacy of Peginterferon alfa-2b in Nucleoside Analogue Experienced Patients with Negative HBeAg and Low HBsAg: A Non-Randomized Clinical Trial. Infect Dis Ther 2021; 10:2259-2270. [PMID: 34309813 PMCID: PMC8572941 DOI: 10.1007/s40121-021-00497-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 06/30/2021] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION Hepatitis B surface antigen (HBsAg) clearance is the treatment goal for hepatitis B e antigen (HBeAg)-negative patients with chronic hepatitis B (CHB). However, its rate is extremely low with nucleoside (acid) analogues (NAs) monotherapy. Peginterferon could enhance HBsAg clearance. This study aimed to evaluate the efficacy of peginterferon alfa-2b (PegIFNα-2b) in NAs-experienced patients with CHB with negative HBeAg and low HBsAg level. METHODS HBeAg-negative patients with CHB who had received NAs therapy over 24 weeks with HBsAg < 1500 IU/mL and HBV DNA < 100 IU/mL were enrolled. Patients received either PegIFNα-2b add-on therapy (n = 108) or continuous NAs monotherapy (n = 75). The primary endpoint was HBsAg clearance rate at week 48. RESULTS At week 48, serum HBV DNA was undetectable among all PegIFNα-2b add-on therapy patients. Almost all patients maintained HBV DNA suppression in the PegIFNα-2b add-on group (100%, 108/108) and NAs monotherapy group (97.33%, 73/75). Only patients with PegIFNα-2b add-on therapy achieved HBsAg clearance (50.93%, 55/108) and HBsAg seroconversion (48.15%, 52/108) at week 48. Patients with baseline HBsAg < 100 IU/mL achieved the highest HBsAg clearance rate and HBsAg seroconversion rate at week 48 (60.87%, 28/46 and 58.70%, 27/46 respectively). HBsAg clearance and HBsAg seroconversion at week 72 had no significant difference with continuing or discontinuing PegIFNα-2b therapy after 48 weeks of treatment. PegIFNα-2b add-on therapy was well tolerated. CONCLUSIONS PegIFNα-2b add-on therapy increases HBsAg clearance rate and seroconversion rate for HBeAg-negative patients with CHB, particularly for those with lower HBsAg level. It would be unnecessary to prolong PegIFNα-2b duration after 48 weeks of PegIFNα-2b treatment.
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Affiliation(s)
- Jun Chen
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Xiangya Road 87, Kaifu District, Changsha, 410008, China.,Key Laboratory of Viral Hepatitis, Hunan, China
| | - Min Qi
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Xiangya Road 87, Kaifu District, Changsha, 410008, China
| | - Xue-Gong Fan
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Xiangya Road 87, Kaifu District, Changsha, 410008, China.,Key Laboratory of Viral Hepatitis, Hunan, China
| | - Xing-Wang Hu
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Xiangya Road 87, Kaifu District, Changsha, 410008, China.,Key Laboratory of Viral Hepatitis, Hunan, China
| | - Cheng-Jin Liao
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Xiangya Road 87, Kaifu District, Changsha, 410008, China
| | - Li-Yuan Long
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Xiangya Road 87, Kaifu District, Changsha, 410008, China
| | - Xiao-Ting Zhao
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Xiangya Road 87, Kaifu District, Changsha, 410008, China
| | - Min Tan
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Xiangya Road 87, Kaifu District, Changsha, 410008, China
| | - Hai-Fu Li
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Xiangya Road 87, Kaifu District, Changsha, 410008, China
| | - Ruo-Chan Chen
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Xiangya Road 87, Kaifu District, Changsha, 410008, China.,Key Laboratory of Viral Hepatitis, Hunan, China
| | - Ze-Bing Huang
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Xiangya Road 87, Kaifu District, Changsha, 410008, China. .,Key Laboratory of Viral Hepatitis, Hunan, China.
| | - Yan Huang
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Xiangya Road 87, Kaifu District, Changsha, 410008, China. .,Key Laboratory of Viral Hepatitis, Hunan, China.
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