Background: An interferon-free regimen including sofosbuvir and ribavirin (RBV) for patients with hepatitis C virus (HCV) genotype 2 (G2) infection leads to a drastic improvement of sustained virological response (SVR). However, the safety, tolerability, and efficacy in patients aged 75 or older have not been completely understood. Summary: Fifty-six patients with HCV G2 infection who were treated with sofosbuvir and weight-based dose of RBV were enrolled. Thirty-seven patients aged ≥75 and 19 patients aged ≤74 were classified as the aged and non-aged groups, respectively. The aged group was characterized by significantly more number of women, history of hepatocellular carcinoma, low serum albumin (ALB) level, low hemoglobin (Hb) concentration, low estimated glomerular filtration rate (eGFR), and high fibrosis-4 index (p = 0.0029). Forty-one patients were evaluated for SVR at 12 weeks after the end of therapy (SVR12); of them, all but one completed the treatment scheduled for 12 weeks. The aged group showed lower SVR12 rate than the non-aged group (81.3% for aged and 96.0% for non-aged groups). Although the Hb concentration and eGFR are significantly lower in the aged group throughout the clinical course, all patients in the aged group completed the 12-week treatment with a gradual increase of serum ALB level. Key Messages: The combination of sofosbuvir plus RBV is tolerable and beneficial in patients aged >75. However, intensive management of anemia by dose reduction of RBV is necessary, which could lead to a low SVR12 rate compared to that observed in patients younger than 75 years.

Kudo M: Surveillance, diagnosis, treatment, and outcome of liver cancer in Japan. Liver Cancer 2015;4:39-50.
Clinical practice guidelines for hepatocellular carcinoma differ between Japan, United States, and Europe. Liver Cancer 2015;4:85-95.
Hsu CS, Chao YC, Lin HH, Chen DS, Kao JH: Systematic review: impact of interferon-based therapy on HCV-related hepatocellular carcinoma. Sci Rep 2015;5:9954.
Ferenci P: Treatment of hepatitis C in difficult-to-treat patients. Nat Rev Gastroenterol Hepatol 2015;12:284-292.
Zeuzem S, Dusheiko GM, Salupere R, Mangia A, Flisiak R, Hyland RH, Illeperuma A, Svarovskaia E, Brainard DM, Symonds WT, Subramanian GM, McHutchison JG, Weiland O, Reesink HW, Ferenci P, Hezode C, Esteban R; VALENCE Investigators: Sofosbuvir and ribavirin in HCV genotypes 2 and 3. N Engl J Med 2014;370:1993-2001.
Ahn SH, Lim YS, Lee KS, Paik SW, Lee YJ, Jeong SH, Kim JH, Yoon SK, Yim HJ, Tak WY, Han SY, Yang JC, Mo H, Mathias A, Han L, Knox SJ, Brainard DM, Kim YJ, Byun KS, Kim YS, Heo J, Han KH: A phase 3b study of sofosbuvir plus ribavirin in treatment-naive and treatment-experienced Korean patients chronically infected with genotype 2 hepatitis C virus. J Viral Hepat 2016;23:358-365.
Younossi ZM, Stepanova M, Zeuzem S, Dusheiko G, Esteban R, Hezode C, Reesink HW, Weiland O, Nader F, Hunt SL: Patient-reported outcomes assessment in chronic hepatitis C treated with sofosbuvir and ribavirin: the VALENCE study. J Hepatol 2014;61:228-234.
Omata M, Nishiguchi S, Ueno Y, Mochizuki H, Izumi N, Ikeda F, Toyoda H, Yokosuka O, Nirei K, Genda T, Umemura T, Takehara T, Sakamoto N, Nishigaki Y, Nakane K, Toda N, Ide T, Yanase M, Hino K, Gao B, Garrison KL, Dvory-Sobol H, Ishizaki A, Omote M, Brainard D, Knox S, Symonds WT, McHutchison JG, Yatsuhashi H, Mizokami M: Sofosbuvir plus ribavirin in Japanese patients with chronic genotype 2 HCV infection: an open-label, phase 3 trial. J Viral Hepat 2014;21:762-768.
Kao JH, Chien RN, Chang TT, Peng CY, Hu TH, Lo GH, Wang HY, Chen JJ, Yang JC, Knox SJ, Han L, Mo H, Mathias A, Brainard DM, Sheen IS, Hsu YC, Chu CJ, Chuang WL: A phase 3b study of sofosbuvir plus ribavirin in Taiwanese patients with chronic genotype 2 hepatitis C virus infection. Liver Int 2016;36:1101-1107.
Naik GS, Tyagi MG: A pharmacological profile of ribavirin and monitoring of its plasma concentration in chronic hepatitis C infection. J Clin Exp Hepatol 2012;2:42-54.
Kudo M, Matsui O, Izumi N, Iijima H, Kadoya M, Imai Y, Okusaka T, Miyayama S, Tsuchiya K, Ueshima K, Hiraoka A, Ikeda M, Ogasawara S, Yamashita T, Minami T, Yamakado K; Liver Cancer Study Group of Japan: JSH consensus-based clinical practice guidelines for the management of hepatocellular carcinoma: 2014 update by the liver cancer study group of Japan. Liver Cancer 2014;3:458-468.
Chung H, Ueda T, Kudo M: Changing trends in hepatitis C infection over the past 50 years in Japan. Intervirology 2010;53:39-43.
Gotte M, Feld JJ: Direct-acting antiviral agents for hepatitis C: structural and mechanistic insights. Nat Rev Gastroenterol Hepatol 2016;13:338-351.
Kohara M, Tanaka T, Tsukiyama-Kohara K, Tanaka S, Mizokami M, Lau JY, Hattori N: Hepatitis C virus genotypes 1 and 2 respond to interferon-alpha with different virologic kinetics. J Infect Dis 1995;172:934-938.
Mangia A, Santoro R, Minerva N, Ricci GL, Carretta V, Persico M, Vinelli F, Scotto G, Bacca D, Annese M, Romano M, Zechini F, Sogari F, Spirito F, Andriulli A: Peginterferon alfa-2b and ribavirin for 12 vs. 24 weeks in HCV genotype 2 or 3. N Engl J Med 2005;352:2609-2617.
Tanaka J, Kumagai J, Katayama K, Komiya Y, Mizui M, Yamanaka R, Suzuki K, Miyakawa Y, Yoshizawa H: Sex- and age-specific carriers of hepatitis B and C viruses in Japan estimated by the prevalence in the 3,485,648 first-time blood donors during 1995-2000. Intervirology 2004;47:32-40.
Vallet-Pichard A, Mallet V, Nalpas B, Verkarre V, Nalpas A, Dhalluin-Venier V, Fontaine H, Pol S: FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. Comparison with liver biopsy and fibrotest. Hepatology 2007;46:32-36.
Toyoda H, Kumada T, Tada T, Sone Y, Kaneoka Y, Maeda A: Tumor markers for hepatocellular carcinoma: simple and significant predictors of outcome in patients with HCC. Liver Cancer 2015;4:126-136.
Kudo M: Risk of hepatocellular carcinoma in patients with hepatitis C virus who achieved sustained virological response. Liver Cancer 2016;5:155-161.
Foster GR, Afdhal N, Roberts SK, Brau N, Gane EJ, Pianko S, Lawitz E, Thompson A, Shiffman ML, Cooper C, Towner WJ, Conway B, Ruane P, Bourliere M, Asselah T, Berg T, Zeuzem S, Rosenberg W, Agarwal K, Stedman CA, Mo H, Dvory-Sobol H, Han L, Wang J, McNally J, Osinusi A, Brainard DM, McHutchison JG, Mazzotta F, Tran TT, Gordon SC, Patel K, Reau N, Mangia A, Sulkowski M; ASTRAL-2 Investigators; ASTRAL-3 Investigators: Sofosbuvir and velpatasvir for HCV genotype 2 and 3 infection. N Engl J Med 2015;373:2608-2617.
Feld JJ, Jacobson IM, Hezode C, Asselah T, Ruane PJ, Gruener N, Abergel A, Mangia A, Lai CL, Chan HL, Mazzotta F, Moreno C, Yoshida E, Shafran SD, Towner WJ, Tran TT, McNally J, Osinusi A, Svarovskaia E, Zhu Y, Brainard DM, McHutchison JG, Agarwal K, Zeuzem S; ASTRAL-1 Investigators: Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med 2015;373:2599-2607.
Curry MP, O'Leary JG, Bzowej N, Muir AJ, Korenblat KM, Fenkel JM, Reddy KR, Lawitz E, Flamm SL, Schiano T, Teperman L, Fontana R, Schiff E, Fried M, Doehle B, An D, McNally J, Osinusi A, Brainard DM, McHutchison JG, Brown RS Jr, Charlton M; ASTRAL-4 Investigators: Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. N Engl J Med 2015;373:2618-2628.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.