Long-Term Outcomes and Dynamics of Mutants Associated with Lamivudine-Adefovir Rescue Therapy in Patients with Lamivudine-Resistant Chronic Hepatitis B.
- Author:
Jihyun KIM
1
;
Sae Hwan LEE
;
Hong Soo KIM
;
Kanghyug CHOI
;
Soung Won JEONG
;
Sang Gyune KIM
;
Jae Young JANG
;
Young Seok KIM
;
Boo Sung KIM
Author Information
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords: Hepatitis B virus; Lamivudine resistance; Restriction fragment mass polymorphism; Mutation
- MeSH: 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
- From:Gut and Liver 2015;9(1):103-108
- CountryRepublic of Korea
- Language:English
- 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.
