라미부딘 치료에 대한 24주 바이러스 반응이 없는 만성 B형 간염환자에서 엔테카비어 전환치료 후에 보인 치료효과 및 바이러스 변이에 대한 분석

Abstract

Purposes : Many data reported that on-treatment response during nucleos(t)ide analogues (NAs) was a good indicator of long-term virological response (VR). Therefore, in patients without VR at 24 weeks of NA therapy with low genetic barriers, it has been recommended to add another drug or change to more potent antiviral agents. We were to clarify the role of switch therapy into more potent antiviral agents.

Materials and methods : We changed the lamivudine (LMV) to entecavir (ETV) (0.5 mg a day) in CHB patients without VR after using the LMV over 24 weeks. Twenty-three patients (including 2 patients receiving clevudine) were included (group A). As a control, we used the patients who received LMV maintenance therapy during same periods (group B, n=16). Genotypic change was analyzed using RFMP method in patients with switched therapy (n=16).

Results : There was no difference between two groups in age, gender, mean levels of HBV DNA (log, 4.1 vs. 4.3), HBeAg positivity (78.3% vs. 87.5%) and duration of lamivudine therapy (74 vs. 71 weeks) before the entry of the study. The cumulative rates of VR at 96 weeks (HBV DNA < 60 IU/mL) were 79% in group A and 29% in group B (p=0.004). Virological breakthrough (VBT) occurred in 2 patient (8.7%) in group A and 10 patients (62.5%) in group B (p <0.001). All patients with VBT except a patient harbored only LMV-related resistant mutant. Seven of 16 patients with RFMP analysis showed LMV-related mutants (mixed or dominant) before switch therapy. Nine of 16 patients without LMV-related mutants before switched therapy, 7 patients showed progressive selection of LMV-related mutants regardless of VR and in 2 patients, genetic change could not be evaluated because of PCR negative just after ETV switch.

Conclusion: Our data suggested that switch to more potent antiviral agents, ETV, might be effective for the patients without VR over 24 weeks of NA therapy with low genetic barriers. However, long-term effect of ETV should be evaluated because gradual selection of LMV-related mutants was common in most patients. Keywords : Virologic response, Entecavior, Genetic change