Characteristics of adefovir resistance in patients with or without lamivudine-resistant hepatitis B virus treated with adefovir: a 4-year experience

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http://onlinelibrary.wiley.com/doi/10.1111/j.1478-3231.2010.02416.x/abstract

Characteristics of adefovir resistance in patients with or without

lamivudine-resistant hepatitis B virus treated with adefovir: a 4-year

experience

Chien-Hung Chen, Jing-Houng Wang, Sheng-Nan Lu, Tsung-Hui Hu, Chao-Hung Hung,

Min-Hui Chang, Chi-Sin Changchien, Chuan-Mo LeeArticle first

published online: 8 DEC 2010

DOI: 10.1111/j.1478-3231.2010.02416.x

© 2010 Wiley & Sons A/S

Issue

Liver International

Volume 31, Issue 2, pages 206–214, February 2011

Abstract

Background/Aim: We investigated the 4-year incidence and predictors of adefovir

resistance in chronic hepatitis B patients with or without lamivudine

(LAM)-resistance treated with adefovir dipivoxil with or without short-term LAM

overlapping.

Methods: One hundred and two LAM-resistant patients and 79 without LAM

resistance (36 naïve and 43 prior LAM exposure) treated with adefovir for >12

months were prospectively examined.

Results: Cumulative incidences of adefovir resistance at month 12, 24, 36 and 48

were 3.9, 21.1, 31.8 and 43% respectively in LAM-resistant patients. Cirrhosis

was a significant risk factor for adefovir resistance. A similar rate of

adefovir resistance was observed for LAM-resistant patients and those with prior

LAM exposure without resistance. Regarding LAM-resistant patients, compared with

those having hepatitis B virus (HBV) DNA levels <300 copies/ml, patients having

HBV DNA levels >104 copies/ml at week 24 of therapy had a hazard ratio (HR) of

9.8 for adefovir resistance development, while those without LAM resistance

having the same HBV DNA levels at week 48 had a similar HR (9.5).

Multidrug-resistant (LAM+adefovir) variants were detected by direct sequencing

in three of 35 LAM-resistant patients treated with a switch to adefovir. Two of

them had resistant mutations to both drugs on the same viral genome as

determined by molecular cloning and sequencing.

Conclusion: The incidence of adefovir resistance was high in LAM-resistant

patients treated with sequential adefovir. High HBV DNA levels at week 24 and 48

of therapy were the strongest predictors for adefovir resistance development in

patients with and without LAM resistance respectively.