Interferon-free regimens for the treatment of hepatitis C virus in liver transplant candidates or recipients

World J Gastroenterol. 2015 August 28; 21(32): 9526-9533.
Published online 2015 August 28. doi: 10.3748/wjg.v21.i32.9526.

Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.

Interferon-free regimens for the treatment of hepatitis C virus in liver transplant candidates or recipients

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.

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.

INTRODUCTION
Chronic hepatitis C (CHC) has infected approximately 3% of the world population[1]. Patients with hepatitis C virus (HCV) infection can develop cirrhosis and hepatocellular carcinoma (HCC)[2,3], while CHC is considered the leading cause for liver transplantation (LT) in many Western countries[4]. The combination of pegylated interferon-α (pegIFN) and ribavirin (RBV) in patients with CHC had relatively low rates of sustained virological response (SVR)[5,6], but during the last years several direct acting antiviral agents (DAAs) have increased the efficacy of antiviral therapy[7].
The first approved DAAs (boceprevir and telaprevir) were associated with high rates of clinical complications, particularly among cirrhotic patients with serum albumin levels ≤ 3.5 g/dL and platelet counts ≤ 100000/mm3[8]. Very recently, newer DAAs have been licensed by the European Medicines Agency and Food and Drug Administration to be used mainly as part of IFN-free combinations offering high SVR rates (> 95%), short treatment duration and excellent safety profiles. These agents include sofosbuvir (Sovaldi, Gilead), the first nucleotide analogue NS5B polymerase inhibitor[9], simeprevir (Olysio, Janssen), a second-wave NS3/4A protease inhibitor (achieving SVR in 77%-92% of genotype 1 CHC patients, compared to 46% under pegIFN plus RBV)[10], daclatasvir (Dankliza, Bristol-Myers Squibb)[11], a NS5A inhibitor, the co-formulation of the NS5A inhibitor ledipasvir with sofosbuvir (Harvoni, Gilead)[12], the co-formulation of a ritonavir boosted NS3/4A protease inhibitor, paritaprevir, with the NS5A inhibitor ombitasvir (Viekirax, Abbvie) and dasabuvir (Exviera, Abbvie), a non-nucleos(t)ide NS5B polymerase inhibitor[13] (Table1). They are all given as one tablet daily, except for paritaprevir/ombitasvir (two tablets once daily) and dasabuvir (1 tablet twice daily). The purpose of this review is to summarize the recent findings concerning the use of the new IFN-free regimens in LT candidates or recipients with CHC.

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