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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 21, 2015; 21(15): 4447-4456
Published online Apr 21, 2015. doi: 10.3748/wjg.v21.i15.4447
Management of hepatitis C infection before and after liver transplantation
Stefano Fagiuoli, Roberto Ravasio, Maria Grazia Lucà, Anna Baldan, Silvia Pecere, Alessandro Vitale, Luisa Pasulo
Stefano Fagiuoli, Maria Grazia Lucà, Anna Baldan, Silvia Pecere, Luisa Pasulo, Gastroenterology and Transplant Hepatology, Papa Giovanni XXIII Hospital, 24127 Bergamo, Italy
Roberto Ravasio, PHarmES Milano, 20133 Milano, Italy
Alessandro Vitale, Liver Transplantation and Hepatobiliary Surgical Unit, Padua University Hospital, 35122 Padua, Italy
Author contributions: All authors made substantial contributions to analysis and interpretation of data, drafting the article or making critical revisions related to important intellectual content; and gave final approval of the version of the article to be published.
Conflict-of-interest: Stefano Fagiuoli has lectured or been involved in Advisory boards for MSD, Gilead, BMS, Janssen, Bayer, Roche, Novartis, Biotest, Kedrion and Abbvie. Roberto Ravasio, Maria Grazia Lucà, Anna Baldan, Silvia Pecere, Alessandro Vitale and Luisa Pasulo, have no interests which might be perceived as posing a conflict or bias.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Stefano Fagiuoli, U.S.C Gastroenterology and Transplant Hepatology, Papa Giovanni XXIII Hospital, Piazza OMS, 1, 24127 Bergamo, Italy. sfagiuoli@hpg23.it
Telephone: +39-035-2673459 Fax: +39-035-2674964
Received: December 19, 2014
Peer-review started: December 21, 2014
First decision: January 22, 2015
Revised: February 11, 2015
Accepted: March 12, 2015
Article in press: March 12, 2015
Published online: April 21, 2015
Processing time: 121 Days and 15.6 Hours
Abstract

Chronic hepatitis C (CHC) is the most common indication for liver transplantation (LT). Aggressive treatment of hepatitis C virus (HCV) infection before cirrhosis development or decompensation may reduce LT need and risk of HCV recurrence post-LT. Factors associated with increased HCV risk or severity of recurrence include older age, immunosuppression, HCV genotype 1 and high viral load at LT. HCV recurrence post-LT leads to accelerated liver disease and cirrhosis development with reduced graft and patient survival. Currently, interferon (IFN)-based regimens can be used in dual-agent regimens with ribavirin, in triple-agent antiviral strategies with direct-acting antivirals (e.g., protease inhibitors telaprevir or boceprevir), or before transplant in compensated patients to reduce HCV viral load to prevent or reduce the risk of post-LT recurrence and complications; they cannot be used in patients with decompensated cirrhosis. IFN-based regimens are used in less than half of HCV-infected patients waiting for LT due to extremely low efficacy and poor tolerability. However, antiviral therapy is indicated after LT in patients with histologically confirmed CHC despite tolerability issues. Improvements in side effect management have increased survival in patients achieving therapeutic targets. HCV treatment pre- and post-LT results in significant health care costs especially when lack of efficacy leads to disease worsening, although studies have shown sofosbuvir treatment before LT vs conventional post-LT dual antiviral is cost effective. The suboptimal efficacy and tolerability of IFN-based therapies, plus the significant economic burden, means the need for effective and well tolerated IFN-free anti-HCV therapy for pre- and post-LT remains high.

Keywords: Hepatitis C virus; Orthotopic liver transplantation; Interferon-free treatment; Decompensated cirrhosis; Chronic hepatitis C

Core tip: This paper discusses alternative treatment options for patients with hepatitis C virus (HCV) undergoing liver transplantation (LT), particularly those with decompensated cirrhosis in whom interferon (IFN)-based therapy is contraindicated. Virtually all patients undergoing LT experience HCV recurrence leading to accelerated liver disease and cirrhosis development with reduced graft and patient survival. Novel IFN-free antiviral therapies featuring better efficacy and tolerability in such patients shall increase sustained virologic response rates while decreasing side effects and drug interactions, thus preventing progression of HCV-related liver disease, decreasing the general costs associated with both HCV treatment and worsening of patient health.