Yongtao Sun

Switching from entecavir to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: A randomised open-label trial (OSST trial)

BACKGROUND & AIMS Durable post-treatment response is uncommon in chronic hepatitis B (CHB) patients on nucleos(t)ide analogue therapy. Response, response predictors and safety were assessed in patients who switched from long-term entecavir (ETV) to peginterferon alfa-2a. METHODS Hepatitis B e antigen (HBeAg)-positive CHB patients who had received ETV for 9-36 months, with HBeAg <100 PEIU/ml and HBV DNA ⩽1000 copies/ml, were randomised 1:1 to receive peginterferon alfa-2a 180 μg/week or ETV 0.5mg/day for 48 weeks. The primary endpoint was HBeAg seroconversion at week 48 (ClinicalTrials.gov: NCT00940485). RESULTS 200 patients were randomised; 197 received ⩾1 study drug dose. Five patients who were anti-HBe-positive at baseline were excluded from the modified intention-to-treat population (peginterferon alfa-2a, n = 94; ETV, n = 98). Patients who switched to peginterferon alfa-2a achieved higher week 48 HBeAg seroconversion rates vs. those who continued ETV (14.9% vs. 6.1%; p = 0.0467). Only patients receiving peginterferon alfa-2a achieved HBsAg loss (8.5%). Among peginterferon alfa-2a-treated patients with HBeAg loss and HBsAg <1500 IU/ml at randomisation, 33.3% and 22.2% achieved HBeAg seroconversion and HBsAg loss, respectively. Early on-treatment HBsAg decline predicted response at week 48; highest rates were observed in patients with week 12 HBsAg <200 IU/ml (HBeAg seroconversion, 66.7%; HBsAg loss, 77.8%). Alanine aminotransferase elevations were not associated with viral rebound (n = 38). Peginterferon alfa-2a was well-tolerated. CONCLUSIONS For patients who achieve virological suppression with ETV, switching to a finite course of peginterferon alfa-2a significantly increases rates of HBeAg seroconversion and HBsAg loss. A response-guided approach may identify patients with the greatest chance of success.

Distribution and clinical correlates of viral and host genotypes in Chinese patients with chronic hepatitis C virus infection.

Chronic hepatitis C virus (HCV) infection is relatively frequent in China. This study investigated the clinical, demographic, and viral and host genetic characteristics that may influence disease manifestations and clinical management.

Quantitative hepatitis B core antibody level is a new predictor for treatment response in HBeAg-positive chronic hepatitis B patients receiving peginterferon.

A recent study revealed that quantitative hepatitis B core antibody (qAnti-HBc) level could serve as a novel marker for predicting treatment response. In the present study, we further investigated the predictive value of qAnti-HBc level in HBeAg-positive patients undergoing PEG-IFN therapy. A total of 140 HBeAg-positive patients who underwent PEG-IFN therapy for 48 weeks and follow-up for 24 weeks were enrolled in this study. Serum samples were taken every 12 weeks post-treatment. The predictive value of the baseline qAnti-HBc level for treatment response was evaluated. Patients were further divided into 2 groups according to the baseline qAnti-HBc level, and the response rate was compared. Additionally, the kinetics of the virological and biochemical parameters were analyzed. Patients who achieved response had a significantly higher baseline qAnti-HBc level (serological response [SR], 4.52±0.36 vs. 4.19±0.58, p=0.001; virological response [VR], 4.53±0.35 vs. 4.22±0.57, p=0.005; combined response [CR], 4.50±0.36 vs. 4.22±0.58, p=0.009)). Baseline qAnti-HBc was the only parameter that was independently correlated with SR (p=0.008), VR (p=0.010) and CR(p=0.019). Patients with baseline qAnti-HBc levels ≥30,000 IU/mL had significantly higher response rates, more HBV DNA suppression, and better hepatitis control in PEG-IFN treatment. In conclusion, qAnti-HBc level may be a novel biomarker for predicting treatment response in HBeAg-positive patients receiving PEG-IFN therapy.

Sustained immune control in HBeAg-positive patients who switched from entecavir therapy to pegylated interferon-α2a: 1 year follow-up of the OSST study.

BACKGROUND In the OSST study, hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients who switched from long-term entecavir (ETV) therapy to pegylated interferon-α2a (PEG-IFN-α2a; 40 kDa) achieved higher rates of HBeAg seroconversion and hepatitis B surface antigen (HBsAg) loss than those who continued ETV. Herein we report the sustainability of serological responses during 1 year of untreated follow-up in patients who switched from ETV to PEG-IFN-α2a therapy. METHODS A total of 62 patients who completed 48 weeks of PEG-IFN-α2a therapy were followed-up for 48 weeks off treatment. Primary end points were HBeAg seroconversion and maintenance of HBeAg seroconversion at 48 weeks post-treatment. Secondary end points included HBsAg loss, HBV DNA <1,000 copies/ml and alanine aminotransferase normalization (<1× upper limit of normal). RESULTS The HBeAg seroconversion rate increased from 17.7% (11/62) at the end of treatment to 38.7% (24/62) 1 year post-treatment. Sustained HBeAg seroconversion was achieved by 63.6% (7/11) patients with end-of-treatment responses, while late HBeAg seroconversion was achieved by 33.3% (17/51) of patients who did not have end-of-treatment responses. Sustained HBsAg loss was documented in 6 of 7 patients, and sustained HBV DNA suppression was achieved in 60% (27/45) of patients with an end-of-treatment response. CONCLUSIONS In patients who do not achieve HBeAg seroconversion during long-term ETV therapy, switching to finite treatment with PEG-IFN-α2a produces HBeAg seroconversion in a substantial proportion of patients at end of treatment and during 1 year of follow-up. Moreover, HBeAg seroconversion and HBsAg loss are sustained in most patients during 1 year of untreated follow-up.

Real-world treatment patterns and clinical outcomes of HCV treatment-naive patients in China: an interim analysis from the CCgenos study

In China, chronic hepatitis C virus (HCV) infection represents a considerable healthcare burden. Although interferon‐based therapy has been the standard‐of‐care for many years, few long‐term, real‐life studies have assessed interferon‐based treatment in China. The objective of CCgenos follow‐up study was to analyze long‐term treatment patterns and outcomes in a cohort of treatment‐naïve, Han ethnic, patients with chronic HCV infection.

Randomized, three-arm study to optimize lamivudine efficacy in hepatitis B e antigen-positive chronic hepatitis B patients

Data about the efficacy of de novo combination therapies, or optimization strategy by adding the other drug based on the virological response at week 24 of low genetic barrier antiviral agents is still limited. This study aimed to compare the efficacy at week 104 of lamivudine monotherapy (MONO), lamivudine plus adefovir dipivoxil (ADV) combination therapy (COMBO), and lamivudine optimization strategy (OPTIMIZE).

Clinical characteristics and current management of hepatitis B and C in China.

AIM To describe a population of outpatients in China infected by hepatitis B virus (HBV) and/or hepatitis C virus (HCV), and assess their current management status. METHODS A multicenter, cross-sectional study of HBV- and/or HCV-infected patients was conducted from August to November, 2011 in western China. Patients ≥ 18 years of age with HBV and/or HCV infections who visited outpatient departments at 10 hospitals were evaluated, whether treated or not. Data were collected on the day of visit from medical records and patient interviews. RESULTS A total 4010 outpatients were analyzed, including 2562 HBV-infected and 1406 HCV-infected and 42 HBV/HCV co-infected patients. The median duration of documented infection was 7.5 years in HBV-infected and 1.8 years in HCV-infected patients. Cirrhosis was the most frequent hepatic complication (12.2%), appearing in one-third of patients within 3 years prior to or at diagnosis. The HCV genotype was determined in only 10% of HCV-infected patients. Biopsy data were only available for 54 patients (1.3%). Antiviral medications had been received by 58.2% of patients with HBV infection and 66.6% with HCV infection. Nucleos(t)ide analogs were the major antiviral medications prescribed for HBV-infected patients (most commonly adefovir dipivoxil and lamivudine). Ribavirin + pegylated interferon was prescribed for two-thirds of HCV-infected patients. In the previous 12 mo, around one-fifth patients had been hospitalized due to HBV or HCV infection. CONCLUSION This observational, real-life study has identified some gaps between clinical practice and guideline recommendations in China. To achieve better health outcomes, several improvements, such as disease monitoring and optimizing antiviral regimens, should be made to improve disease management.

Response-guided peginterferon therapy in patients with HBeAg-positive chronic hepatitis B: A randomized controlled study

BACKGROUND & AIMS Response-guided therapy has been confirmed to be an effective strategy for the treatment of chronic hepatitis C in the pegylated interferon (PegIFN) era, but no randomized trial utilizing this strategy has been conducted in chronic hepatitis B. METHODS In this open-label, multicenter, randomized trial, HBeAg positive patients were treated with PegIFN (180μg/week) for 24weeks. Early responders (HBsAg <1500IU/ml and HBV DNA <10(5)copies/ml at week 24) received PegIFN for a further 24weeks (arm A), while non-early responders were randomized to PegIFN for another 24weeks (arm B), another 72weeks (arm C) or PegIFN for another 72weeks plus adefovir for 36weeks (arm D). The primary endpoint was the change of quantitative HBsAg from baseline to the end of follow-up (EOF). RESULTS For non-early responders, 96-week PegIFN monotherapy did not lead to a greater reduction of HBsAg from baseline to EOF, compared with 48-week PegIFN (-0.71 vs. -0.67log10IU/ml, P=0.407). The rate of HBeAg seroconversion with HBV DNA <2000IU/ml at EOF were similar for arms B, C and D (17.9%, 23.9% and 25.0% respectively). For patients with HBsAg <1500IU/ml or HBV DNA <10(5)copies/ml at week 24, 38.4% and 37.0% achieved HBeAg seroconversion with HBV DNA <2000IU/ml at EOF respectively. CONCLUSIONS Patients with HBsAg <1500IU/ml or HBV DNA <10(5)copies/ml at week 24 would benefit from continued PegIFN treatment. Extending the duration of PegIFN with or without adding adefovir did not show superiority over 48weeks PegIFN monotherapy. LAY SUMMARY Extending the duration of pegylated interferon (PegIFN) alfa-2a is not recommended in HBeAg positive patients as treatment extension beyond 48weeks did not show convincing benefit. Patients who achieved HBsAg <1500IU/ml or HBV DNA <10(5)copies/ml after 24-week PegIFNα-2a showed satisfactory outcome after the withdrawal of finite PegIFNα-2a treatment. CLINICAL TRIAL NUMBER NCT01086085.

Prevalence of abnormal glycometabolism in treatment‐naive patients with hepatitis C virus infection in a Chinese Han population

The hepatitis C virus (HCV) may promote pancreatic β‐cell apoptosis‐like cell death through a caspase 3‐dependent pathway, initiating the onset of type 2 diabetes mellitus (T2DM); however, the risk factors for development of T2DM and other abnormal glycometabolic factors in HCV patients of the Chinese Han ethnicity have been poorly explored.

P414 ASSESSMENT OF THE CHANGE IN ESTIMATED GLOMERULAR FILTRATION RATES IN TELBIVUDINE- OR LAMIVUDINE-BASED TRERAPY IN PATIENTS WITH CHRONIC HEPATITIS B

P414 ASSESSMENT OF THE CHANGE IN ESTIMATED GLOMERULAR FILTRATION RATES IN TELBIVUDINEOR LAMIVUDINE-BASED TRERAPY IN PATIENTS WITH CHRONIC HEPATITIS B J. Sun, J. Cheng, X. Chen, Q. Xie, D. Tan, H. Wang, S. Chen, Y. Yu, H. Tang, J. Niu, J. Sheng, Y. Sun, Q. Ning, M. Wan, X. Bai, G. Shi, H. Ren, M. Xu, X. Dou, J. Shi, J. Jiang, X. Chen, H. Long, M. Wang, H. Zhang, Z. Gao, C. Chen, J. Jiang, H. Ma, J. Jia, J. Hou. Hepatology Unit, Nanfang Hospital, Guangzhou, Beijing Ditan Hospital, Beijing Youan Hospital, Beijing, Ruijin Hospital, Shanghai, Xiangya Hospital, Changsha, Peking University People’s Hospital, Beijing, Ji’nan Infectious Diseases Hospital, Ji’nan, First Hospital of Peking University, Beijing, Huaxi Hospital, Chengdu, No. 1 Hospital Affiliated to Jilin University, Changchun, Zhejiang University 1st Affiliated Hospital, Hangzhou, Tangdu Hospital, Xi’an, Tongji Hospital, Wuhan, Changhai Hospital, Shanghai Huashan Hospital, Shanghai, Chongqing Medical University 2nd Affiliated Hospital, Chongqing, 8th People’s Hospital, Guangzhou, Shengjing Hospital, Shenyang, 6th People’s Hospital, Hangzhou, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangdong General Hospital, Guangzhou, The First People Hospital of Foshan, Foshan, 81st PLA Hospital, Guangzhou, 302nd PLA Hospital, Beijing, Sun Yat-Sen University 3rd Affiliated Hospital, Guangzhou, 85th PLA Hospital, Shanghai, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Beijing Friendship Hospital, Beijing, China E-mail: doctorsunjian@qq.com Background and Aims: Recent pooled analyses of multiple studies of telbivudine in patients with chronic hepatitis B (CHB) demonstrated that telbivudine therapy was associated with a consistent increase of estimated Glomerular Filtration Rates (eGFR). The aim of this study was to validate the effect on eGFR of telbivudineor lamivudine-based therapy in two multi-center, randomized controlled studies in Chinese CHB patients. Methods: 606 and 366 compensated HBeAg positive CHB patients were enrolled in the EFFORT (NCT00962533) and EXPLORE (NCT01088009) studies with similar study design based on ROADMAP concept, receiving telbivudine-based and lamivudinebased therapies for up to 104 weeks, respectively. Adefovir was added to patients per protocol at baseline or week 28, or at virological breakthrough. eGFR was assessed with aMDRD equation.