Retrospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 7, 2015; 21(9): 2746-2753
Published online Mar 7, 2015. doi: 10.3748/wjg.v21.i9.2746
Tenofovir disoproxil fumarate is superior to lamivudine plus adefovir in lamivudine-resistant chronic hepatitis B patients
Dan-Hong Yang, Yuan-Jun Xie, Nian-Feng Zhao, Hong-Ying Pan, Ming-Wei Li, Hai-Jun Huang
Dan-Hong Yang, Hong-Ying Pan, Hai-Jun Huang, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, Hangzhou 310014, Zhejiang Province, China
Yuan-Jun Xie, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
Nian-Feng Zhao, Ming-Wei Li, Department of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Author contributions: Yang DH designed the study, analyzed the data, and drafted the manuscript; Xie YJ, Zhao NF and Pan HY collected the data; Pan HY was also involved in drafting the manuscript; Li MW and Huang HJ performed the experiments.
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-Ying Pan, MD, Director, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, No. 158 Shangtang Road, Hangzhou 310014, Zhejiang Province, China. panhy2014@163.com
Telephone: +86-571-85893602 Fax: +86-571-85131448
Received: July 26, 2014
Peer-review started: July 26, 2014
First decision: August 15, 2014
Revised: September 8, 2014
Accepted: December 5, 2014
Article in press: December 8, 2014
Published online: March 7, 2015
Abstract

AIM: To assess the efficacy of tenofovir disoproxil fumarate (TDF) in lamivudine (LAM)-resistant patients with a suboptimal response to LAM plus adefovir (ADV).

METHODS: We retrospectively analyzed the efficacy of switching to tenofovir disoproxil fumarate in suboptimal responders to lamivudine plus adefovir. Charts were reviewed for LAM-resistant chronic hepatitis B (CHB) patients who visited the Zhejiang Province People’s Hospital and The First Affiliated Hospital, College of Medicine, Zhejiang University, from June 2009 to May 2013. Patients whose serum hepatitis B virus (HBV) DNA remained detectable despite at least 6 mo of LAM plus ADV combination therapy were included. Patients with a suboptimal response to LAM plus ADV were randomized to switch to TDF monotherapy (300 mg/d orally; TDF group) or to continuation with LAM (100 mg/d orally) plus ADV (10 mg/d orally; LAM plus ADV group) and were followed for 48 wk. Serum HBV DNA was determined at baseline and weeks 4, 12, 24, 36, and 48. HBV serological markers and biochemistry were assessed at baseline and weeks 12, 24, and 48. Resistance surveillance and side effects were monitored during therapy.

RESULTS: Fifty-nine patient were randomized to switch to TDF (n = 28) or continuation with LAM plus ADV (n = 31). No significant differences were found between the groups at baseline. Prior to TDF therapy, all patients had been exposed to LAM plus ADV for a median of 11 mo (range: 6-24 mo). No difference was seen in baseline serum HBV DNA between the two groups [5.13 ± 1.08 log10 copies/mL (TDF) vs 5.04 ± 31.16 log10 copies/mL (LAM + ADV), P = 0.639]. There was no significant difference in the rates of achieving complete virological response (CVR) at week 4 between the TDF and LAM + ADV groups (17.86% vs 6.45%, P = 0.24). The rate of achieving CVR in the TDF and LAM plus ADV groups was 75% vs 16.13% at week 12, 82.14% vs 22.58% at week 24, 89.29% vs 25.81% at week 36, and 96.43% vs 29.03% at week 48, respectively (P < 0.001). The rate of alanine aminotransferase normalization was significantly higher in the TDF than in the LAM plus ADV group at week 12 (75% vs 17.86%, P < 0.001), but not at week 24 (78.57% vs 54.84%, P = 0.097) or 48 (89.26% vs 67.74%, P = 0.062). Patients were hepatitis B e antigen (HBeAg) positive at baseline. There was no significant difference in HBeAg negativity between the TDF and LAM plus ADV groups at week 48 (4% vs 0%, P = 0.481). There were no drug-related adverse effects at week 48 in either group.

CONCLUSION: Switching to TDF monotherapy was superior to continuous add-on therapy in patients with LAM-resistant CHB with a suboptimal response to LAM plus ADV.

Keywords: Hepatitis B virus, Adefovir, Lamivudine, Tenofovir disoproxil fumarate, Viral resistance

Core tip: We retrospectively assessed the efficacy of switching to tenofovir disoproxil fumarate (TDF) monotherapy and continuous lamivudine (LAM) plus adefovir (ADV) combination therapy in LAM-resistant chronic hepatitis B (CHB) patients with suboptimal response to LAM plus ADV. Switching to TDF was effective and safe for LAM-resistant CHB patients and exerted stronger antiviral activity than continuous add-on therapy at week 48. Our findings suggest that suboptimal responders to LAM plus ADV should be switched as soon as possible to antiviral agents with higher potency, and TDF would be a viable option.