标题: Characteristics of adefovir resistance in patients with or without lamivudine-re [打印本页] 作者: StephenW 时间: 2011-1-5 22:27 标题: Characteristics of adefovir resistance in patients with or without lamivudine-re
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.