Gut Liver.  2015 Jan;9(1):103-108. 10.5009/gnl14018.

Long-Term Outcomes and Dynamics of Mutants Associated with Lamivudine-Adefovir Rescue Therapy in Patients with Lamivudine-Resistant Chronic Hepatitis B

• Kim J
• Lee SH
• Kim HS
• Choi K
• Jeong SW
• Kim SG
• Jang JY
• Kim YS
• Kim BS

• KMID: 2380789
• DOI: http://doi.org/10.5009/gnl14018

Abstract

BACKGROUND/AIMS
To investigate the association between the baseline profiles and dynamics of hepatitis B virus (HBV) DNA polymerase gene mutations and the long-term virological response of lamivudine (LAM)-adefovir (ADV) combination therapy in patients with LAM-resistant chronic hepatitis B.
METHODS
Seventy-five patients who received LAM-ADV combination therapy for more than 12 months were analyzed. Restriction fragment mass polymorphism assays were used to detect and monitor the dynamics of LAM- and ADV-resistant mutations.
RESULTS
The median duration of LAM-ADV combination therapy was 26 months (range, 12 to 58 months). The baseline mutation profiles, rtM204I (p=0.992), rtM204I/V (p=0.177), and rtL180M (p=0.051), were not correlated with the cumulative virological response, and the baseline HBV DNA level (p=0.032) was the only independent predictive factor for cumulative virological response. Tests for LAM- and ADV-resistant mutations were performed in 12 suboptimal responders in weeks 48 and 96. The population of rtM204 mutants persisted or increased in 8 of 12 patients, and rtA181T mutants newly emerged as a minor population in four patients until 96 weeks. Nevertheless, the viral loads progressively decreased during rescue therapy, and these dynamics did not correlate with virological response.
CONCLUSIONS
The baseline profile and dynamics of LAM-resistant mutations during LAM-ADV combination therapy are not associated with a virological response.

Keyword

Hepatitis B virus; Lamivudine resistance; Restriction fragment mass polymorphism; Mutation

MeSH Terms

Adenine/administration & dosage/*analogs & derivatives/therapeutic use
Adult
Aged
Aged, 80 and over
Antiviral Agents/administration & dosage/*therapeutic use
DNA-Directed DNA Polymerase/genetics
Drug Resistance, Viral/genetics
Drug Therapy, Combination
Female
Hepatitis B virus/*genetics
Hepatitis B, Chronic/*drug therapy/virology
Humans
Lamivudine/administration & dosage/*therapeutic use
Male
Middle Aged
Organophosphonates/administration & dosage/*therapeutic use
Treatment Outcome
Viral Load/drug effects
Young Adult
Adenine
Antiviral Agents
DNA-Directed DNA Polymerase
Lamivudine
Organophosphonates