Simeprevir-Based Triple Therapy with Reduced Doses of Pegylated Interferon α-2a Plus Ribavirin for Interferon Ineligible Patients with Genotype 1b Hepatitis C Virus
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Background/Aims: The present study aimed to evaluate the safety and efficacy of simeprevir-based triple therapy with reduced doses of pegylated interferon (PEG-IFN) and ribavirin for interferon (IFN) ineligible patients, such as elderly and/or cirrhotic patients, and to elucidate the factors contributing to a sustained virologic response (SVR). Methods: One hundred IFN ineligible patients infected with genotype 1b hepatitis C virus (HCV) were treated. Simeprevir (100 mg) was given orally together with reduced doses of PEG-IFN-α 2a (90 μg), and ribavirin (200 mg less than the recommended dose). Results: The patients’ median age was 70 years, and 70 patients were cirrhotic. Three patients (3%) discontinued treatment due to adverse events. The SVR rate was 64%. Factors that significantly contributed to the SVR included the γ-glutamyl transferase and α-fetoprotein levels, interleukin- 28B (IL28B) polymorphism status, and the level and reduction of HCV RNA at weeks 2 and 4. The multivariate analysis showed that the IL28B polymorphism status was the only independent factor that predicted the SVR, with a positive predictive value of 77%. Conclusions: Simeprevir-based triple therapy with reduced doses of PEG-IFN and ribavirin was safe and effective for IFN ineligible patients infected with genotype 1b HCV. IL28B polymorphism status was a useful predictor of the SVR.
Abstract
Background/Aims: The present study aimed to evaluate the safety and efficacy of simeprevir-based triple therapy with reduced doses of pegylated interferon (PEG-IFN) and ribavirin for interferon (IFN) ineligible patients, such as elderly and/or cirrhotic patients, and to elucidate the factors contributing to a sustained virologic response (SVR). Methods: One hundred IFN ineligible patients infected with genotype 1b hepatitis C virus (HCV) were treated. Simeprevir (100 mg) was given orally together with reduced doses of PEG-IFN-α 2a (90 μg), and ribavirin (200 mg less than the recommended dose). Results: The patients’ median age was 70 years, and 70 patients were cirrhotic. Three patients (3%) discontinued treatment due to adverse events. The SVR rate was 64%. Factors that significantly contributed to the SVR included the γ-glutamyl transferase and α-fetoprotein levels, interleukin- 28B (IL28B) polymorphism status, and the level and reduction of HCV RNA at weeks 2 and 4. The multivariate analysis showed that the IL28B polymorphism status was the only independent factor that predicted the SVR, with a positive predictive value of 77%. Conclusions: Simeprevir-based triple therapy with reduced doses of PEG-IFN and ribavirin was safe and effective for IFN ineligible patients infected with genotype 1b HCV. IL28B polymorphism status was a useful predictor of the SVR.
참고문헌 (28)
- Asahina Y, "Effect of aging on risk for hepatocellular carcinoma in chronic hepatitis C virus infection", Hepatology, 52, pp.518~527 (2010)
- Editors of the Drafting Committee for Hepatitis Management Guidelines: the Japan Society of Hepatology, "Guidelines for the management of hepatitis c virus infection: first edition, May 2012, The Japan Society of Hepatology", Hepatol Res, 43, pp.1~34 (2013)
- Huang CF, "Efficacy and safety of pegylated interferon combined with ribavirin for the treatment of older patients with chronic hepatitis C", J Infect Dis, 201, pp.751~759 (2010)
- Bota S, "Severe adverse events during antiviral therapy in hepatitis C virus cirrhotic patients: a systematic review", World J Hepatol, 5, pp.120~126 (2013)
- Di Marco V, "Peg-interferon alone or combined with ribavirin in HCV cirrhosis with portal hypertension: a randomized controlled trial", J Hepatol, 47, pp.484~491 (2007)
- 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)
- Roffi L, "Pegylated interferon-alpha2b plus ribavirin: an efficacious and well-tolerated treatment regimen for patients with hepatitis C virus related histologically proven cirrhosis", Antivir Ther, 13, pp.663~673 (2008)
- Tamai H, "Prediction of sustained response to low-dose pegylated interferon alpha-2b plus ribavirin in patients with genotype 1b and high hepatitis C virus level using viral reduction within 2 weeks after therapy initiation", Hepatol Res, 41, pp.1137~1144 (2011)
- Tamai H, "Low-dose pegylated interferon- alpha2a plus ribavirin therapy for elderly and", or cirrhotic patients with HCV genotype-1b and high viral load, 2014, pp.19, 107~115
- Kumada H, "Telaprevir with peginterferon and ribavirin for treatment- naive patients chronically infected with HCV of genotype 1 in Japan", J Hepatol, 56, pp.78~84 (2012)
- Tamai H, "Prediction of sustained virological response to telaprevir-based triple therapy using viral response within 2 weeks", Hepat Res Treat, 2014, pp.748935~ (2014)
- Fried MW, "Once-daily simeprevir (TMC435) with pegylated interferon and ribavirin in treatment-naïve genotype 1 hepatitis C: the randomized PILLAR study", Hepatology, 58, pp.1918~1929 (2013)
- Jacobson IM, "Simeprevir with pegylated interferon alfa 2a plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-1): a phase 3, randomised, double-blind, placebo-controlled trial", Lancet, 384, pp.403~413 (2014)
- Manns M, "Simeprevir with pegylated interferon alfa 2a or 2b plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-2): a randomised, double-blind, placebo-controlled phase 3 trial", Lancet, 384, pp.414~426 (2014)
- Hayashi N, "Simeprevir with peginterferon", ribavirin for treatment-naive hepatitis C genotype 1 patients in Japan: CONCERTO-1, a phase III trial, 2014, pp.61, 219~227
- Simmonds P, "Classification of hepatitis C virus into six major genotypes and a series of subtypes by phylogenetic analysis of the NS-5 region", J Gen Virol, 74(Pt 11), pp.2391~2399 (1993)
- Enomoto N, "Mutations in the nonstructural protein 5A gene and response to interferon in patients with chronic hepatitis C virus 1b infection", N Engl J Med, 334, pp.77~81 (1996)
- Akuta N, "Association of amino acid substitution pattern in core protein of hepatitis C virus genotype 1b high viral load and non-virological response to interferonribavirin combination therapy", Intervirology, 48, pp.372~380 (2005)
- Tanaka Y, "Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C", Nat Genet, 41, pp.1105~1109 (2009)
- Roomer R, "Risk factors for infection during treatment with peginterferon alfa and ribavirin for chronic hepatitis C", Hepatology, 52, pp.1225~1231 (2010)
- Ogawa E, "Comparative effectiveness and safety study of triple therapy with simeprevir or telaprevir for non-cirrhotic patients with chronic hepatitis C virus genotype 1b infection", J Gastroenterol Hepatol, 30, pp.1759~1767 (2015)
- Tahata Y, "Impact of ribavirin dosage in chronic hepatitis C patients treated with simeprevir, pegylated interferon plus ribavirin combination therapy", J Med Virol, 88, pp.1776~1784 (2016)
- Izumi N, "Once-daily simeprevir with peginterferon and ribavirin for treatment-experienced HCV genotype 1-infected patients in Japan: the CONCERTO-2 and CONCERTO- 3 studies", J Gastroenterol, 49, pp.941~953 (2014)
- Reddy KR, "Simeprevir versus telaprevir with peginterferon and ribavirin in previous null or partial responders with chronic hepatitis C virus genotype 1 infection (ATTAIN): a randomised, double-blind, non-inferiority phase 3 trial", Lancet Infect Dis, 15, pp.27~35 (2015)
- Ogawa E, "Effectiveness of triple therapy with simeprevir for chronic hepatitis C genotype 1b patients with prior telaprevir failure", J Viral Hepat, 22, pp.992~1001 (2015)
- Ogawa E, "Comparative safety study on severe anemia by simeprevir versus telaprevir-based triple therapy for chronic hepatitis C", J Gastroenterol Hepatol, 30, pp.1309~1316 (2015)
- Tahata Y, "The impact of an inosine triphosphate pyrophosphatase genotype on bilirubin increase in chronic hepatitis C patients treated with simeprevir, pegylated interferon plus ribavirin", J Gastroenterol, 51, pp.252~259 (2016)
- Hayashi K, "Usefulness of a new immuno-radiometric assay to detect hepatitis C core antigen in a community-based population", J Viral Hepat, 12, pp.106~110 (2005)