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
Processing time: 54 Days and 17.7 Hours
ARTICLE HIGHLIGHTS
Research background

Recurrent infection with hepatitis C virus (HCV) following liver transplant (LT) treatment is the leading cause of liver graft loss and death in liver-transplanted patients infected with HCV. Before introduction of the direct-acting antiviral (DAA) therapies, treatment options for recurrent HCV in liver-transplanted patients were limited, due to significant drug-drug interactions and severe side effects. The approval of DAAs has revolutionized HCV treatment.

Research motivation

Despite the growing number of successfully treated patients, HCV recurrence after orthotopic LT remains one of the most challenging clinical situations. Thus, analysis of real-world cohorts of LT recipients may provide valuable insights into the safety and efficacy of DAA treatment in these cohorts.

Research objectives

To analyze the safety and efficiency of DAA regimens in liver-transplanted patients with HCV reinfection in a real-world cohort.

Research methods

The study cohort comprises all liver transplanted patients that were treated with direct acting antiviral regimen at the Heidelberg University Hospital from January 2014 to December 2016. In total 39 patients were included. Clinical and laboratory baseline characteristics were collected at entry into the study. All patients were at least six months liver transplanted before antiviral therapy was started. HCV treatment was administered by the outpatient clinic at our tertiary center. The decision about the HCV treatment was made by specialists at our transplant center, according to current available or recommended medication. Patients were treated according recommendations of available drugs after approval by FDA and EMEA. As different drugs were approved during the course of this study therapy regimen were adapted. In the beginning Sofosbuvir was combined with pegylated interferon (Peg-INF) and ribavirin. After introduction of Daclatasvir, Simeprivir and fixed-dose combination of Sofosbuvir with Ledipasvir interferon containing regimen were no longer perpetuated.

Research results

At the end of the study period, all thirty-nine patients had attained SVR at 24 wk (SVR24). 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.

Research conclusions

In conclusion, DAAs are safe and very efficient in HCV patients after liver transplantation, even in cases of recurrent cirrhosis or history of relapse after Peg-IFN therapy. The high SVR rates in our cohort, despite the many patients with rrecurrent cirrhosis, may argue for a 24-wk therapy period in patients with risk factors for therapy failure in a posttransplant setting.

Research perspectives

HCV recurrence after orthotopic LT can be safely and efficiently treated with DAAs. Optimal timing and duration of antiviral therapy remains undetermined. Patients at risk for relapse need to be identified before initiation of therapy. Long-term effects of successful antiviral therapy, especially in patients with advanced recurrent cirrhosis, need to be analyzed in future.