Five years of treatment with adefovir dipivoxil in Chinese patients with HBeAg-positive chronic hepatitis B.

Abstract

BACKGROUND:

Adefovir dipivoxil (ADV) is a nucleotide analogue with proven efficacy in chronic hepatitis B (CHB).

AIMS:

This study investigated long-term ADV treatment in HBeAg-positive patients.

METHODS:

A total of 480 Chinese subjects with HBeAg-positive CHB who participated in a 1-year, double-blind, placebo-controlled study of ADV 10 mg daily were offered open-label continuation for a further 208 weeks.

RESULTS:

A total of 390 subjects completed 5 years of treatment. Baseline median hepatitis B virus (HBV) DNA was 8.8 log(10) copies/ml and alanine aminotransferase (ALT) 2.6 × upper limit of normal. Treatment with ADV resulted in sustained suppression of median HBV DNA by 4.8, 5.0, 5.1, 5.4 and 5.5 log(10) copies/ml after 1, 2, 3, 4 and 5 years respectively. Continuous treatment with ADV led to a progressive increase in the proportion of subjects achieving undetectable HBV DNA, from 28% after 1 year to 58% after 5 years. HBeAg seroconversion rates increased cumulatively from 11% after 1 year to 29% after 5 years. HBsAg seroconversion was achieved by 1.0% of patients. ADV resulted in ALT normalization that was maintained throughout this study in 75-79% of subjects. Virological breakthrough associated with ADV resistant mutations (rtN236T and rtA181V) occurred in 14.6% of subjects. ADV was well tolerated.

CONCLUSION:

Five years of ADV treatment in Chinese subjects with HBeAg-positive CHB resulted in increasing virological and serological responses and sustained biochemical responses over time. Virological resistance was identified in 14.6% of patients. Urgent switch or add-on therapy with a nucleoside analogue is necessary if ADV resistant mutations are detected, particularly rtN236T. Treatment was well tolerated.

• Authors: Zeng Minde, Mao Yimin, Yao Guangbi, Hou JinLin, Wang Hao, Ren Hong, Wang Yuming, Zhou Xiaqiu, Xu Daozhen, Chen Yagang, Niu Junqi, Chen Youming, Wang Yaozong, Jonathan Dixon, Keith Barker
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 32 Issue 1 Pg. 137-46 (Jan 2012) ISSN: 1478-3231 [Electronic] United States
• PMID: 22097972 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 John Wiley & Sons A/S.

Chemical References

• Antiviral Agents
• DNA, Viral
• Hepatitis B e Antigens
• Organophosphonates
• Adenine
• adefovir dipivoxil

Topics

• Adenine (analogs & derivatives, therapeutic use)
• Adolescent
• Adult
• Antiviral Agents (therapeutic use)
• Asian People
• DNA, Viral (analysis)
• Drug Resistance, Viral (genetics)
• Female
• Hepatitis B e Antigens (blood)
• Hepatitis B virus (genetics, immunology)
• Hepatitis B, Chronic (diagnosis, drug therapy, virology)
• Humans
• Liver Function Tests
• Male
• Middle Aged
• Mutation (drug effects)
• Organophosphonates (therapeutic use)
• Treatment Outcome
• Viral Load (drug effects)
• Viremia (drug therapy)
• Young Adult