Observational Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 28, 2018; 24(12): 1353-1360
Published online Mar 28, 2018. doi: 10.3748/wjg.v24.i12.1353
Successful combination of direct antiviral agents in liver-transplanted patients with recurrent hepatitis C virus
Christian Rupp, Theresa Hippchen, Manuel Neuberger, Peter Sauer, Jan Pfeiffenberger, Wolfgang Stremmel, Daniel Nils Gotthardt, Arianeb Mehrabi, Karl-Heinz Weiss
Christian Rupp, Theresa Hippchen, Manuel Neuberger, Peter Sauer, Jan Pfeiffenberger, Wolfgang Stremmel, Daniel Nils Gotthardt, Karl-Heinz Weiss, Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg 69120, Germany
Christian Rupp, Peter Sauer, Interdisciplinary Endoscopy Unit, University Hospital of Heidelberg, Heidelberg 69120, Germany
Arianeb Mehrabi, Department of General, Visceral and Transplantation Surgery, University Hospital of Heidelberg, Heidelberg 69120, Germany
Author contributions: Rupp C, Hippchen T, Neuberger M, Sauer P, Gotthardt DN, Mehrabi A and Weiss KH contributed to the treatment and follow-up of patients; Rupp C, Hippchen T, Gotthardt DN and Weiss KH performed the statistical analyses; Rupp C, Sauer P, Stremmel W and Weiss KH conceived of the article and drafted the manuscript.
Supported by “Deutsche Forschungsgemeinschaft” to Rupp C and Gotthardt DN.
Institutional review board statement: This study was reviewed and approved for publication by the Institutional Review Board of the University Hospital of Heidelberg (Approval No. S-043/2011).
Informed consent statement: All study participants, or their legal guardian, provided written informed consent prior to study enrollment.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: The original anonymized dataset is available upon request from the Corresponding Author at: christian.rupp@med.uni-heidelberg.de.
STROBE statement: The authors have read the STROBE Statement - checklist of items, and the manuscript was prepared and revised according to the STROBE Statement - checklist of items.
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: Christian Rupp, MD, Department of Internal Medicine IV, University Hospital of Heidelberg, Im Neuenheimer Feld 410, Heidelberg 69120, Germany. christian_rupp@med.uni-heidelberg.de
Telephone: +49-6221-5636817 Fax: +49-6221-568904
Received: January 30, 2018
Peer-review started: January 31, 2018
First decision: February 24, 2018
Revised: March 2, 2018
Accepted: March 18, 2018
Article in press: March 18, 2018
Published online: March 28, 2018
Abstract
AIM

To analyze the safety and efficiency of direct-acting antiviral (DAA) regimens in liver-transplanted patients with hepatitis C virus (HCV) reinfection.

METHODS

Between January 2014 and December 2016, 39 patients with HCV reinfection after liver transplantation were treated at our tertiary referral center with sofosbuvir (SOF)-based regimens, including various combinations with interferon (IFN), daclatasvir (DAC), simeprivir (SIM) and/or ledipasvir (LDV). Thirteen patients were treated with SOF + IFN ± RBV. Ten patients were treated with SOF + DAC ± RBV. Fiveteen patients were treated with fixed-dose combination of SOF + LDV ± RBV. One patient was treated with SOF + SIM + RBV. Three patients with relapse were retreated with SOF + LDV + RBV. The treatment duration was 12-24 wk in all cases. The decision about the HCV treatment was made by specialists at our transplant center, according to current available or recommended medications.

RESULTS

The majority of patients were IFN-experienced (29/39, 74.4%) and had a history of hepatocellular carcinoma (26/39, 66.7%) before liver transplantation. Sustained virological response at 12 wk (SVR12) was achieved in 10/13 (76.9%) of patients treated with SOF + IFN ± RBV. All patients with relapse were treated with fixed-dose combination of SOF + LDV + RBV. Patients treated with SOF + DAC + RBV or SOF + LDV + RBV achieved 100% SVR12. SVR rates after combination treatment with inhibitors of the HCV nonstructural protein (NS)5A and NS5B for 24 wk were significantly higher, as compared to all other therapy regimens (P = 0.007). Liver function was stable or even improved in the majority of patients during treatment. All antiviral therapies were safe and well-tolerated, without need of discontinuation of treatment or dose adjustment of immunosuppression. No serious adverse events or any harm to the liver graft became overt. No patient experienced acute cellular rejection during the study period.

CONCLUSION

Our cohort of liver-transplanted patients achieved high rates of SVR12 after a 24-wk course of treatment, especially with combination of NS5A and NS5B inhibitors.

Keywords: Hepatitis C virus, Recurrence, Direct acting antivirals, Liver transplantation, Sustained virological response

Core tip: We examined the safety and efficiency of novel direct-acting antiviral agents (DAAs) in liver-transplanted patients with recurrence of hepatitis c virus (HCV) infection in a real-world cohort at our tertiary care center. In conclusion, DAAs are safe and very efficient in HCV patients after liver transplantation, even in case of recurrent cirrhosis or history of relapse after pegylated-interferon therapy. The high sustained virological response rates in our cohort, despite many patients with recurrent cirrhosis, may argue for a 24-wk therapy period in patients with risk factors for therapy failure in a posttransplant setting.