Efficacy and safety of daclatasvir plus asunaprevir for Korean patients with HCV genotype Ib infection: a retrospective multi-institutional study
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Background/Aims: The combination of daclatasvir (DCV) and asunaprevir (ASV) has demonstrated a high sustained virologic response at 12 weeks (SVR12) and a low rate of adverse events in previous clinical studies. The purpose of this study was to clarify the results of treatment and side effects in Korean patients with chronic hepatitis C virus (HCV) genotype Ib infection. Methods: We retrospectively analyzed clinical data from chronic HCV genotype Ib patients treated with DCV+ASV from August 2015 to September 2016 at five hospitals in the Daejeon-Chungcheong area. Results: A total of 152 patients were examined for resistance associated variants (RAVs). Among them, 15 (9.9%) were positive for Y93 and one (0.7%) was positive for L31. Of 126 patients treated with DCV+ASV, 83 patients completed treatment and 76 patients were included in safety and efficacy analysis. Five (6.6%) were positive for Y93 and 12 (15.8%) exhibited cirrhotic change. DCV+ASV was the first-line treatment for 58 (76.3%) patients. Eleven (14.5%) patients relapsed after previous treatment that included interferon and seven (9.2%) of these patients were found to be intolerant of interferon. Adverse events occurred in 10 (13.2%) patients and two patients stopped the medication because of severe itching and skin rash. SVR12 was 89.5% (68/76) in all patients and 91.5% (65/71) in RAV-negative patients. Conclusions: DCV+ASV showed good efficacy in patients with HCV Ib infection in Korea. Close monitoring is needed for severe adverse events and treatment failure, which were uncommon.
Abstract
Background/Aims: The combination of daclatasvir (DCV) and asunaprevir (ASV) has demonstrated a high sustained virologic response at 12 weeks (SVR12) and a low rate of adverse events in previous clinical studies. The purpose of this study was to clarify the results of treatment and side effects in Korean patients with chronic hepatitis C virus (HCV) genotype Ib infection. Methods: We retrospectively analyzed clinical data from chronic HCV genotype Ib patients treated with DCV+ASV from August 2015 to September 2016 at five hospitals in the Daejeon-Chungcheong area. Results: A total of 152 patients were examined for resistance associated variants (RAVs). Among them, 15 (9.9%) were positive for Y93 and one (0.7%) was positive for L31. Of 126 patients treated with DCV+ASV, 83 patients completed treatment and 76 patients were included in safety and efficacy analysis. Five (6.6%) were positive for Y93 and 12 (15.8%) exhibited cirrhotic change. DCV+ASV was the first-line treatment for 58 (76.3%) patients. Eleven (14.5%) patients relapsed after previous treatment that included interferon and seven (9.2%) of these patients were found to be intolerant of interferon. Adverse events occurred in 10 (13.2%) patients and two patients stopped the medication because of severe itching and skin rash. SVR12 was 89.5% (68/76) in all patients and 91.5% (65/71) in RAV-negative patients. Conclusions: DCV+ASV showed good efficacy in patients with HCV Ib infection in Korea. Close monitoring is needed for severe adverse events and treatment failure, which were uncommon.
참고문헌 (21)
- Webster DP, "Hepatitis C", Lancet, 385, pp.1124~1135 (2015)
- AASLD, "IDSA HCV Guidance Panel", Hepatitis C guidance: AASLDIDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus, 2015, pp.62, 932~954
- Korean Association for the Study of the Liver, "KASL clinical practice guidelines: management of hepatitis C", Clin Mol Hepatol, 22, pp.76~139 (2016)
- European Association for Study of Liver, "EASL recommendations on treatment of hepatitis C 2015", J Hepatol, 63, pp.199~236 (2015)
- Gao M, "Antiviral activity and resistance of HCV NS5A replication complex inhibitors", Curr Opin Virol, 3, pp.514~520 (2013)
- McPhee F, "Preclinical profile and characterization of the hepatitis C virus NS3protease inhibitor asunaprevir (BMS-650032)", Antimicrob Agents Chemother, 56, pp.5387~5396 (2012)
- Lok AS, "Preliminary study of two antiviral agents for hepatitis C genotype 1", N Engl J Med, 366, pp.216~224 (2012)
- Seong MH, "Clinical and epidemiological features of hepatitis C virus infection in South Korea: a prospective, multicenter cohort study", J Med Virol, 85, pp.1724~1733 (2013)
- Kao JH, "All-oral daclatasvir plus asunaprevir for chronic hepatitis C virus (HCV) genotype 1b infection: a sub-analysis in Asian patients from the HALLMARK DUAL study", Liver Int, 36, pp.1433~1441 (2016)
- Kumada H, "Daclatasvir plus asunaprevir for chronic HCV genotype 1b infection", Hepatology, 59, pp.2083~2091 (2014)
- Bartels DJ, "Hepatitis C virus variants with decreased sensitivity to directacting antivirals (DAAs) were rarely observed in DAA-naive patients prior to treatment", J Virol, 87, pp.1544~1553 (2013)
- Karino Y, "Characterization of virologic escape in hepatitis C virus genotype 1b patients treated with the direct-acting antivirals daclatasvir and asunaprevir", J Hepatol, 58, pp.646~654 (2013)
- Miura M, "Deep sequencing analysis of variants resistant to the non-structural 5A inhibitor daclatasvir in patients with genotype 1b hepatitis C virus infection", Hepatol Res, 44, pp.E360~E367 (2014)
- Manns M, "All-oral daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: a multinational, phase 3, multicohort study", Lancet, 384, pp.1597~1605 (2014)
- Itakura J, "Naturally occurring, resistance-associated hepatitis C virus NS5A variants are linked to interleukin-28B genotype and are sensitive to interferon-based therapy", Hepatol Res, 45, pp.E115~E121 (2015)
- Bruno S, "Efficacy and safety of peginterferon alfa-2a (40KD) plus ribavirin in hepatitis C patients with advanced fibrosis and cirrhosis", Hepatology, 51, pp.388~397 (2010)
- Bourlière M, "Future treatment of patients with HCV cirrhosis", Liver Int, 32(Suppl 1), pp.113~119 (2012)
- Muir AJ, "Daclatasvir in combination with asunaprevir and beclabuvir for hepatitis C virus genotype 1 infection with compensated cirrhosis", JAMA, 313, pp.1736~1744 (2015)
- 남희철, "Efficacy and safety of daclatasvir and asunaprevir for hepatitis C virus genotype 1b infection", Clinical and Molecular Hepatology, 22(2), pp.259~266 (2016), 대한간학회
- Patel P, "Cutaneous adverse events in chronic hepatitis C patients treated with new direct-acting antivirals:a systematic review and meta-analysis", J Cutan Med Surg, 20, pp.58~66 (2016)
- "Fact sheet N°164: hepatitis C"[URL]