Daclatasvir plus Asunaprevir for Chronic Hepatitis C Virus Genotype 1b Infection; Real Life Data in Korea

Abstract

Background The most prevalent subtype of hepatitis C virus (HCV) in Korea is genotype 1b. Until recently, pegylated interferon alfa and ribavirin for 48 weeks was the only approved therapy for genotype 1b chronic HCV infection with limited efficacy. All oral combination therapy with novel direct acting antivirals daclatasvir and asunaprevir for 24 weeks has provided high sustained virologic response (SVR) rate in genotype 1b patients. We conducted an interim analysis of real life data in Korean patients with genotype 1b HCV infection who were treated with daclatasvir plus asunaprevir.

Method One hundred fifty three patients with chronic HCV genotype 1b infection were treated with daclatasvir plus asunaprevir in Korea University Hospital from July, 2015. After excluding three patients who were loss to follow up, one hundred fifty patients were analyzed. HCV RNA at baseline, 4, 12, 24 weeks were assayed with laboratory tests. NS5A resistant associated variant (RAV) were evaluated at baseline. Virologic breakthrough was defined as increase from nadir of greater than 1 log10 in HCV RNA or HCV RNA of 20 IU/mL or greater after a measurement of less than 20 IU/mL. Lower limit of HCV RNA quantification was 20 IU/ml. Significant adverse events were defined as more than grade 3 according to CTCAE v4.0.

Results Mean age was 59 years, 107 patients were treatment naïve (71.3%), and 41 patients had liver cirrhosis (27.3%), among which 18 had evidence of varices on endoscopic examination. NS5A RAV was observed in 4 patients (all Y93 positive). Median treatment duration was 20 weeks. 73 patients finished 24 weeks therapy (3 virologic breakthroughs), while 12 patients stopped during therapy (4 virologic breakthroughs, 2 adverse events, 4 economic burden, 1 HCC recur, 1 death from variceal bleeding), and 65 patients were on treatment. HCV RNA was not detected in 129/132 patients at 4 weeks (97.7%), 112/116 patients at 12 weeks (96.6%), and 73/79 patients at 24 weeks (92.4%) Adverse event was observed in 39 patients (36%), including 2 significant adverse events (1 aminotransferase > 5 times UNL, 1 myalgia). Virologic breakthrough was not observed in patients with RAV. SVR rate will be analyzed after further follow up.

Conclusion In our patients, daclatasvir plus asunaprevir showed comparable efficacy and safety with previous clinical studies. More data in large population are needed including SVR results.