Management options for lamivudine-resistant chronic hepatitis B patients with suboptimal virological suppression by adefovir

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http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2011.04833.x/abstract

Management options for lamivudine-resistant chronic hepatitis B patients with

suboptimal virological suppression by adefovir

A. Ong1,2,3, V. W.-S. Wong1,2, G. L.-H. Wong1,2, H.-Y. Chan1,2, C.-H. Tse1,2, H.

L.-Y. Chan1,2

Article first published online: 24 AUG 2011

DOI: 10.1111/j.1365-2036.2011.04833.x

© 2011 Blackwell Publishing Ltd

Issue

Alimentary Pharmacology & Therapeutics

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

Summary

Background  In chronic hepatitis B (CHB) patients, adefovir is commonly used

as a rescue therapy for lamivudine resistance, but often results in incomplete

virological suppression.

Aim  To study the factors predicting response to adefovir rescue, and the

treatment response of tenofovir and entecavir in suboptimal responders to

adefovir in CHB patients.

Methods  Chronic hepatitis B patients who took adefovir for at least 6 months

for lamivudine resistance were studied. Early virological response was defined

as undetectable HBV DNA at month 6. Maintained virological response was defined

as undetectable HBV DNA till the last follow-up.

Results  Among 136 patients on adefovir for 39 (5–117) months, 30 (22%) had

early virological response. The 3-year cumulative probability of maintained

virological response was similar between patients on adefovir monotherapy (n =

53, 57.9%) and those on combination of lamivudine and adefovir treatment (n =

83, 56.5%). The month 6 HBV DNA was the only independent factor associated with

maintained virological response (adjusted hazard ratio 0.49, 95% confidence

interval 0.37–0.65, P < 0.001). Twenty-six of 30 (87%) early responders and 36

of 106 (34%) non-early responders had maintained virological response on

adefovir (P < 0.001). Among 106 non-early responders, 18 and 11 were switched to

tenofovir and entecavir, respectively. The 1-year cumulative probability of

maintained virological response was higher in patients switched to tenofovir

(87.5%) than those switched to entecavir (37.5%; P = 0.048) or continued with

adefovir (8.7%; P < 0.001).

Conclusions  In adefovir rescue for lamivudine resistance, month 6 HBV DNA

predicts maintained virological response in CHB patients. Switching to tenofovir

achieved best viral suppression among suboptimal responders to adefovir.