Virological breakthrough and resistance in patients with chronic hepatitis B receiving nucleos(t)ide analogs in clinical practice

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Viral Hepatitis

Virological breakthrough and resistance in patients with chronic hepatitis B

receiving nucleos(t)ide analogs in clinical practice

Chanunta Hongthanakorn, Watcharasak Chotiyaputta, Oberhelman, J.

Fontana, A. Marrero, Licari, S.F. Lok,†DOI:

10.1002/hep.24318

Copyright © 2011 American Association for the Study of Liver Diseases

Issue

Hepatology

Accepted Article (Accepted, unedited articles published online for future

issues)

Abstract

Virological breakthrough (VBT) is the first manifestation of antiviral drug

resistance during nucleos(t)ide analog (NUC) treatment of chronic hepatitis B

(CHB) but not all VBTs are due to drug resistance. The aims of this study were

to determine the incidence of virological breakthrough (VBT) and genotypic

resistance (GR) in CHB patients receiving NUCs in clinical practice. Records of

CHB patients receiving NUCs were reviewed. All patients with VBT were tested for

drug resistance mutations. Of 148 patients included, 73% were men, mean age was

44.9 years. During a mean follow-up of 37.5±20.1 months, 39 (26%) patients had

at least 1 VBT. Of these 39 patients, 15 (38%) were not confirmed to have VBT on

retesting and 10 of these 15 had no evidence of GR. The cumulative probability

of VBT, confirmed VBT, and GR at 5 years was 46.1%, 29.7%, and 33.9%,

respectively. In multivariate analysis, failure to achieve undetectable HBV DNA

was the only factor significantly associated with VBT. Among the 10 patients who

had VBT but no confirmed VBT or GR and who were maintained on the same

medications, serum HBV DNA decreased in all 10 and 9 had undetectable HBV DNA a

mean of 6.8 months after the VBT. Four patients had persistently undetectable

HBV DNA while six had transient increase in HBV DNA during follow-up but none

had GR.

Conclusion: VBT was common in CHB patients receiving NUCs in clinical practice,

but nearly 40% of the VBTs were not related to antiviral drug resistance.

Counseling of CHB patients on medication adherence and confirmation of VBT

and/or GR can avoid unnecessary changes in antiviral medications.

(HEPATOLOGY 2011.)