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

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http://onlinelibrary.wiley.com/doi/10.1111/j.1478-3231.2011.02641.x/abstract

Five years of treatment with adefovir dipivoxil in Chinese patients with

HBeAg-positive chronic hepatitis B

Zeng Minde1,†, Mao Yimin1,*,‡, Yao Guangbi2,†, Hou JinLin3,†, Wang Hao4,†, Ren

Hong5,†, Wang Yuming6,†, Zhou Xiaqiu7,†, Xu Daozhen8,†, Chen Yagang9,†, Niu

Junqi10,†, Chen Youming11,†, Wang Yaozong12,†, Dixon13,§,

Barker13,§

Article first published online: 19 SEP 2011

DOI: 10.1111/j.1478-3231.2011.02641.x

© 2011 Wiley & Sons A/S

Issue

Liver International

Early View (Online Version of Record published before inclusion in an issue)

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 log10 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 log10 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.

[Guest guest]

http://onlinelibrary.wiley.com/doi/10.1111/j.1478-3231.2011.02641.x/abstract

Five years of treatment with adefovir dipivoxil in Chinese patients with

HBeAg-positive chronic hepatitis B

Zeng Minde1,†, Mao Yimin1,*,‡, Yao Guangbi2,†, Hou JinLin3,†, Wang Hao4,†, Ren

Hong5,†, Wang Yuming6,†, Zhou Xiaqiu7,†, Xu Daozhen8,†, Chen Yagang9,†, Niu

Junqi10,†, Chen Youming11,†, Wang Yaozong12,†, Dixon13,§,

Barker13,§

Article first published online: 19 SEP 2011

DOI: 10.1111/j.1478-3231.2011.02641.x

© 2011 Wiley & Sons A/S

Issue

Liver International

Early View (Online Version of Record published before inclusion in an issue)

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 log10 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 log10 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.