우리나라의 실제 임상에서 1b 유전자형 만성 C형 간염의 치료로 Daclatasvir, Asunaprevir 병합요법의 효과 및 안정성에 대한 분석

Abstract

Bmon and difficult to treat genotype worldwide under the treatment of pegylated interferon and ribavirin. The ackground/Aims : HCV genotype I has been known to be the most comenhanced anti-viral effect of combining two direct-acting antiviral (DAA) agents, Daclatasvir and Asunaprevir, has been studied and are now representative treatments in this population. However, Real-world data of the treatment efficacy and safety of the combined drug in Korean patients is lacking.

Methods : A total of 231 HCV genotype Ib patients treated with Daclatasvir 60mg once daily and Asunaprevir 100mg twice daily for 24 weeks were retrospectively reviewed from 4 centers of the Gwang-Ju/Jeon Nam province from August 2015 to October 2016. The treatment efficacy (HCV RNA < 25 IU/mL at post-treatment week 12 (sustained virologic response 12, SVR 12)) of the combined treatment was the primary endpoint for the analysis. Various clinical parameters including patient demographics, Child-Pugh score, presence of baseline resistance associated substitutions (RAS), HCV RNA and adverse effects to treatment were analyzed.

Results : The study included 176 treatment-naïve patients (76.2%), 43 non-responders (18.6%), and 12 intolerable/ineligible (5.2%) patients to previous treatment of pegylated interferon and ribavirin. The presence for RAS at baseline was positive in 9 patients (3.9%) among the tested 223 patients (96.5%). Ninety-nine patients were eligible for evaluation of end of treatment response (ETR) or sustained virologic response (SVR). The proportion of patients with SVR12 was 87.9% (87/99). Prominent alanine/aspartate aminotransferase increase (> 200 U/L) was noted in 1 patient (0.4%). Fatigue (9.1%), headache (4.8%), nausea (3.9%), asthenia (2.2%) and diarrhea (0.8%) were noted but did not lead to discontinuation of therapy. The presence of RAS at baseline was predictive of lower SVR12 rates (p<0.001). Patients with positive HCV RNA at week 8 of treatment had a significant risk of not achieving SVR12 (p=0.030). SVR12

Conclusion : Treatment of HCV genotype 1b infection with Daclatasvir and Asunaprevir in Korean patients resulted in high rates of SVR with low rates of adverse events. Consideration of daclatasvir and asunaprevir treatment in HCV genotype Ib patients without RAS is a feasible treatment option in Korea.

Key words : 1b genotype chronic hepatitis C, Direct acting agent (DAA), Sustained virological response (SVR)