Retrospective Cohort Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 28, 2015; 21(32): 9598-9606
Published online Aug 28, 2015. doi: 10.3748/wjg.v21.i32.9598
Histological outcome for chronic hepatitis B patients treated with entecavir vs lamivudine-based therapy
Jia-Li Wang, Xin-Fang Du, Shao-Long Chen, Yi-Qi Yu, Jing Wang, Xi-Qi Hu, Ling-Yun Shao, Jia-Zhen Chen, Xin-Hua Weng, Wen-Hong Zhang
Jia-Li Wang, Shao-Long Chen, Yi-Qi Yu, Jing Wang, Ling-Yun Shao, Jia-Zhen Chen, Xin-Hua Weng, Wen-Hong Zhang, Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China
Xin-Fang Du, Department of Infectious Diseases, Beilun People’s Hospital, Ningbo 315800, Zhejiang Province, China
Xi-Qi Hu, Department of Pathology, Shanghai Medical College, Fudan University, Shanghai 200032, China
Wen-Hong Zhang, Key Laboratory of Medical Molecular Virology, Ministry of Education and Health, Shanghai Medical College, and Institutes of Biomedical Science, Fudan University, Shanghai 200032, China
Author contributions: Wang JL and Du XF contributed equally to this work; Wang JL performed the analysis, interpreted the data, and drafted the article; Du XF collected all of the human material and clinical data; Chen SL, Yu YQ and Wang J were involved in editing the manuscript; Hu XQ evaluated all of the biopsy specimens as a pathologist; Shao LY coordinated the collection of data and was involved in data analysis; Chen JZ performed the experiments; Weng XH and Zhang WH designed the study and revised the manuscript.
Supported by (In part) Key Medical Specialties Fund of Shanghai Municipal Health Bureau, No. 05II011 2-1.
Institutional review board statement: This study was reviewed by the ethics committees of Fudan University Affiliated Huashan Hospital and Beilun People’s Hospital. The committees waived the ethical approval documents because it was a retrospective study.
Informed consent statement: All study participants or their legal guardian provided informed written consent to liver biopsy. Informed consent was not obtained prior to study enrollment because this is a retrospective study and all study participants were de-identified.
Conflict-of-interest statement: There is no conflict of interest for any of the authors.
Data sharing statement: No additional data are available.
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: Wen-Hong Zhang, Professor, Department of Infectious Diseases, Huashan Hospital, 12 Wulumuqi Zhong Road, Shanghai 200040, China. zhangwenhong@fudan.edu.cn
Telephone: +86-21-52888123 Fax: +86-21-62489015
Received: January 29, 2015
Peer-review started: January 30, 2015
First decision: March 10, 2015
Revised: April 16, 2015
Accepted: June 9, 2015
Article in press: June 10, 2015
Published online: August 28, 2015
Processing time: 211 Days and 3.2 Hours
Abstract

AIM: To compare the histological outcome of chronic hepatitis B (CHB) patients treated with entecavir (ETV) or lamivudine (LAM)-based therapy.

METHODS: We conducted a retrospective analysis of data from 42 CHB patients with advanced fibrosis (baseline Ishak score ≥ 2) or cirrhosis who were treated with ETV or LAM-based therapy in Beilun People’s Hospital, Ningbo between January 2005 and May 2012. The patients enrolled were more than 16 years of age and underwent a minimum of 12 mo of antiviral therapy. We collected data on the baseline characteristics of each patient and obtained paired liver biopsies pre- and post-treatment. The Knodell scoring system and Ishak fibrosis scores were used to evaluate each example. An improvement or worsening of necroinflammation was defined as ≥ 2-point change in the Knodell inflammatory score. The progression or regression of fibrosis was defined as ≥ 1-point change in the Ishak fibrosis score. The continuous variables were compared using t-test or Mann-Whitney test, and the binary variables were compared using χ2 test or Fisher’s exact test. The results of paired liver biopsies were compared with a Wilcoxon signed rank test.

RESULTS: Nineteen patients were treated with ETV and 23 patients were treated with LAM therapy for a mean duration of 39 and 42 mo, respectively. After long-term antiviral treatment, 94.74% (18/19) of the patients in the ETV arm and 95.65% (22/23) in the LAM arm achieved an HBV DNA level less than 1000 IU/mL. The majority of the patients (94.74% in the ETV arm and 73.91% in the LAM arm) had normalized ALT levels. The median Knodell necroinflammatory score decreased from 11 to 0 in the patients receiving ETV, and the median Knodell score decreased from 9 to 3 in the patients receiving LAM (P = 0.0002 and < 0.0001, respectively). The median Ishak fibrosis score showed a 1-point reduction in ETV-treated patients and a 2-point reduction in LAM-treated patients (P = 0.0019 and 0.0205, respectively). The patients receiving ETV showed a more significant improvement in necroinflammation than the LAM-treated patients (P = 0.0003). However, there was no significant difference in fibrotic improvement between the two arms. Furthermore, two patients in each arm achieved a fibrosis score of 0 post-treatment, which indicates a full reversion of fibrosis after antiviral therapy.

CONCLUSION: CHB patients with advanced fibrosis or cirrhosis benefit from antiviral treatment. ETV is superior to LAM therapy in improving necroinflammatory but not fibrotic outcome.

Keywords: Advanced fibrosis; Chronic hepatitis B; Cirrhosis; Entecavir; Histological outcome; Lamivudine

Core tip: This retrospective cohort study compared the histological outcomes of long-term antiviral treatment for an average of more than 3 years with entecavir monotherapy or lamivudine-based combination therapy in chronic hepatitis B patients with significant fibrosis or cirrhosis. There was a histological improvement observed in the majority of patients in both arms. There were also improved virological responses, alanine aminotransferase normalization, and serological responses. Additionally, 4 of 48 patients achieved a full reversion of fibrosis or cirrhosis. Entecavir was superior to lamivudine-based therapy in improving necroinflammatory but not fibrotic outcome.