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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 28, 2015; 21(32): 9526-9533
Published online Aug 28, 2015. doi: 10.3748/wjg.v21.i32.9526
Interferon-free regimens for the treatment of hepatitis C virus in liver transplant candidates or recipients
Evangelos Cholongitas, Chrysoula Pipili, George Papatheodoridis
Evangelos Cholongitas, 4th Department of Internal Medicine, Medical School of Aristotle University, Hippokration General Hospital of Thessaloniki, 54642 Thessaloniki, Greece
Chrysoula Pipili, Division of Nephrology, Royal Infirmary of Edinburgh, Scotland EH16 4SA, United Kingdom
George Papatheodoridis, Department of Gastroenterology, Athens University Medical School, Laiko General Hospital of Athens, 11527 Athens, Greece
Author contributions: Cholongitas E and Pipili C performed the literature search, wrote the first draft of the manuscript and approved the final version; Papatheodoridis GV wrote and edited the final draft of the manuscript and approved the final version.
Conflict-of-interest statement: Cholongitas E: advisor/consultant/sponsored lectures for Bristol- Myers Squibb, Gilead, Novartis; Pipili C: none; Papatheodoridis GV: grant/research support from Abbvie, Bristol- Myers Squibb, Gilead, Janssen, Roche; advisor/consultant for Abbvie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Janssen, Merck Sharp and Dohme, Novartis, Roche; sponsored lectures for Abbvie, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Janssen, Merck Sharp and Dohme, Novartis, Roche; Data Safety Management Board for Gilead.
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: Evangelos Cholongitas, Assistant Professor of Internal Medicine, 4th Department of Internal Medicine, Medical School of Aristotle University, Hippokration General Hospital of Thessaloniki, 49, Konstantinopoleos Street, 54642 Thessaloniki, Greece. cholongitas@yahoo.gr
Telephone: +30-231-0892110 Fax: +30-231-0855566
Received: March 14, 2015
Peer-review started: March 16, 2015
First decision: May 18, 2015
Revised: May 27, 2015
Accepted: July 18, 2015
Article in press: July 18, 2015
Published online: August 28, 2015
Processing time: 167 Days and 10.9 Hours
Abstract

The goal of therapy in chronic hepatitis C virus (HCV) infection is sustained virological response (SVR) which reflects HCV eradication. Treatment against HCV has dramatically improved with the recent availability of direct-acting antivirals (DAAs) including sofosbuvir, simeprevir, daclatasvir, ledipasvir/sofosbuvir, paritaprevir/ombitasvir and dasabuvir. Carefully selected combinations of these DAAs offer the potential for highly effective all-oral safe regimens even for patients with decompensated cirrhosis or liver transplant (LT) recipients. Like all current protease inhibitors, simeprevir and paritaprevir should not be used in patients with Child C cirrhosis, while sofosbuvir and ledipasvir/sofosbuvir should not be given in patients with severe renal impairment and glomerular filtration rate less than 30 mL/min. Drug-drug interactions may still occur with the current DAAs particularly in post-LT patients, in whom simeprevir should not be co-administered with cyclosporine and dose adjustments of calcineurin inhibitors are required in case of regimens including the ritonavir boosted paritaprevir. Phase II clinical trials and real life cohort studies have shown that sofosbuvir based combinations are safe and can achieve improvements of clinical status, high SVR rates and even prevention of post-LT HCV recurrence in patients with decompensated cirrhosis or LT-candidates. In the post-LT setting, sofosbuvir based regimens and the combination of paritaprevir/ombitasvir and dasabuvir have been reported to be safe and achieve high SVR rates, similar to those in non-transplant patients, being effective even in cases with cholestatic fibrosing hepatitis. Ongoing clinical trials and rapidly emerging real life data will further clarify the safety and efficacy of the new regimens in these settings.

Keywords: Hepatitis C; Direct acting antiviral agents; Liver transplantation; Decompensated cirrhosis; Sofosbuvir

Core tip: Treatment against hepatitis C virus has dramatically improved with the novel direct-acting antivirals (DAAs). The currently available DAAs are sofosbuvir, simeprevir, daclatasvir, ledipasvir/sofosbuvir, paritaprevir/ombitasvir and dasabuvir. IFN-free combinations of these novel DAAs with or without ribavirin give excellent sustained virological response in patients with decompensated cirrhosis awaiting liver transplantation and those with recurrence of hepatitis C post liver transplantation. More data regarding the safety and efficacy of these new DAAs are needed, but ongoing clinical trials and real life data will clarify better these issues.