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©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 14, 2015; 21(2): 653-660
Published online Jan 14, 2015. doi: 10.3748/wjg.v21.i2.653
Response-guided treatment of cirrhotic chronic hepatitis B patients: Multicenter prospective study
Er-Li Gu, Yi-Qi Yu, Jia-Li Wang, Yan-Yan Ji, Xiu-Yun Ma, Qing Xie, Hong-Ying Pan, Shan-Min Wu, Jun Li, Cheng-Wei Chen, Xiao-Wei Xu, Yue-Er Wang, Guang-Bi Yao, Hong Wang, Wen-Hong Zhang
Er-Li Gu, Yan-Yan Ji, Yue-Er Wang, Guang-Bi Yao, Hong Wang, Department of Gastroenterology and Hepatology, Jing’an District Central Hospital, Jing’an Branch of Huashan Hospital, Fudan University, Shanghai 200040, China
Yi-Qi Yu, Jia-Li Wang, Wen-Hong Zhang, Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China
Xiu-Yun Ma, Department of Infectious Diseases, Ditan Hospital, Beijing 100011, China
Qing Xie, Department of Hepatology, Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China
Hong-Ying Pan, Department of Infectious Diseases, The 6th People’s Hospital of Hangzhou, Hangzhou 310018, Zhejiang Province, China
Shan-Min Wu, Shanghai Public Health Clincal Center, Shanghai 201508, China
Jun Li, Department of Infectious Diseases, Jiangsu Provincial Hospital, Nanjing 210024, Jiangsu Province, China
Cheng-Wei Chen, Department of Hepatology, Shanghai Liver Disease Research Center of Nanjing Military Area, Shanghai 200235, China
Xiao-Wei Xu, Department of Infectious Diseases, The 1st Affiliated Hospital of Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Wen-Hong Zhang, MOH and MOE Key Laboratory of Medical Molecular Virology, Shanghai Medical College, Fudan University, Shanghai 200032, China
Wen-Hong Zhang, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
Author contributions: Gu EL and Yu YQ contributed equally to this work; Yao GB, Wang H and Zhang WH designed research; Gu EL, Ji YY, Ma XY, Xie Q, Pan HY, Wu SM, Li J, Chen CW, Xu XW and Wang YE performed research; Gu EL analyzed data; Gu EL, Yu YQ, Wang H and Zhang WH wrote the paper.
Supported by Grants from Key Medical Specialties Fund of Shanghai Municipal Health Bureau (partially), No. 05II 011 2-1; and GlaxoSmithKline (China) Investment Co, Ltd, Project 110353.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Hong Wang, MD, Department of Gastroenterology and Hepatology, Jing’an District Central Hospital, Jing’an Branch of Huashan Hospital, Fudan University, No. 259 Xikang Road, Shanghai 200040, China. wanghongjzx@aliyun.com
Telephone: +86-21-61578016 Fax: +86-21-62794791
Received: May 22, 2014
Peer-review started: May 22, 2014
First decision: June 18, 2014
Revised: July 3, 2014
Accepted: July 25, 2014
Article in press: July 25, 2014
Published online: January 14, 2015
AIM: To observe the effect of response-guided add-on therapy with adefovir (ADV) and lamivudine (LAM) in cirrhotic hepatitis B (CHB) patients.
METHODS: A total of 100 patients with CHB and cirrhosis were divided into three arms according to hepatitis B virus (HBV) DNA level after 24 wk LAM monotherapy: Arm A (complete response, HBV DNA ≤ 60 IU/mL, n = 49), Arm B (partial response, HBV DNA: 60-2000 IU/mL, n = 31) and Arm C (inadequate response, HBV DNA > 2000 IU/mL, n = 20). ADV was added to LAM at week 48 in Arms A and B, but at week 24 in Arm C. Virological response, YMDD mutations, biochemical response, and liver function were evaluated.
RESULTS: Comparison of the three arms demonstrated that early complete virologic response at week 24 was associated with maintained viral suppression (undetectable rate of HBV DNA at week 144 was 95.96%, 66.67% and 35.29%, respectively, P = 0.000) and reduced YMDD mutations (mutation rate at week 144 was 0%, 3.23% and 15%, respectively, P = 0.015) after 144 wk treatment. For patients who failed to achieve complete virological response at week 24, switching to combination therapy further decreased HBV DNA level by 1 log10 IU/mL. All three arms obtained biochemical benefits including decline of alanine aminotransferase and elevation of albumin. In patients who developed HBV DNA breakthrough for YMDD mutations, ADV add-on therapy did not induce further multiple drug resistance to LAM or ADV.
CONCLUSION: Optimized response-guided add-on therapy of ADV and LAM maintains long-term suppression of HBV DNA and improves liver function in CHB patients with compensated liver cirrhosis.
Core tip: We conducted this prospective cohort study to explore an optimized strategy of adding adefovir (ADV) and lamivudine (LAM) at different time points according to the early virological response, and to observe its association with long-term treatment outcomes in cirrhotic hepatitis B (CHB) patients with compensated cirrhosis. We found that optimized response-guided add-on therapy of ADV and LAM maintains long-term suppression of hepatitis B virus DNA and improves liver function in CHB patients with compensated liver cirrhosis.
