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KMID : 1188320150090010103
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Gut and Liver
2015 Volume.9 No. 1 p.103 ~ p.108
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Long-Term Outcomes and Dynamics of Mutants Associated with Lamivudine-Adefovir Rescue Therapy in Patients with Lamivudine-Resistant Chronic Hepatitis B
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Kim Ji-hyun
Lee Sae-Hwan
Kim Hong-Soo
Choi Kang-Hyug
Jeong Soung-Won
Kim Sang-Gyune
Jang Jae-Young
Kim Young-Seok
Kim Boo-Sung
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Abstract
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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.
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KEYWORD
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Hepatitis B virus, Lamivudine resistance, Restriction fragment mass polymorphism, Mutation
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