Viral genotype and baseline load predict the response to adefovir treatment

2002落叶

Journal of Hepatology
Volume 47, Issue 3, September 2007, Pages 366-372

Viral genotype and baseline load predict the response to adefovir treatment
in lamivudine-resistant chronic hepatitis B patients

M. Buti, a, , I. Elefsiniotisa, R. Jardia, V. Vargasa, F. Rodriguez-Friasa,
M. Schappera, S. Bonovasa and R. Estebana
aLiver Unit and Biochemistry Department, Hospital Universitario Vall d’
Hebron and CIBER-EHD, Barcelona, Spain
Received 3 January 2007;  revised 6 March 2007;  accepted 3 April 2007. 
Associate Editor: G.K.K. Lau.  Available online 24 May 2007.

Background/Aims

To determine the factors associated with virological response (VR), HBeAg
loss or the emergence of adefovir (ADV)-related mutations in ADV-treated
chronic hepatitis B (CHB) patients with lamivudine (LAM) resistance.

Methods

Fifty-four LAM-resistant CHB patients (46% HBeAg-positive) were treated with
ADV monotherapy (n = 28) or ADV plus LAM (n = 26) for a mean of 30.4 months.

Results

Thirty-eight patients (70.4%) achieved VR defined as HBV-DNA levels <104
copies/ml within the first 12 months of treatment. Six (24%) of 25
HBeAg-positive patients exhibited HBeAg loss and 20% seroconverted to
anti-HBe. Eight patients (14.8%) developed ADV-related mutations. In the
multivariate analysis, female gender (HR = 0.20, 95% CI: 0.05–0.76, p =
0.018), HBeAg-negative (HR = 0.37, 95% CI: 0.14–0.96, p = 0.040) and low
baseline HBV-DNA levels (HR = 0.65, 95% CI: 0.45–0.95, p = 0.027) were
independent predictors of VR, whereas low HBV-DNA levels (HR = 0.36, 95% CI:
0.11–1.20, p = 0.095) and HBV-genotype D (HR = 0.06, 95% CI: 0.004–0.84, p =
0.037) independently predicted HBeAg loss.

Conclusions

ADV therapy suppresses viral replication in more than 70% of LAM-R patients.
Factors associated with virologic response are female gender, HBeAg-negative
status and low baseline serum HBV-DNA levels. Genotype D HBV infection and
low baseline HBV-DNA levels independently predict HBeAg loss.