Case Report
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 28, 2016; 22(8): 2630-2635
Published online Feb 28, 2016. doi: 10.3748/wjg.v22.i8.2630
Ombitasvir, paritaprevir, ritonavir, dasabuvir and ribavirin in cirrhosis after complete destruction of hepatocellular carcinoma
Zahariy Krastev, Deian Jelev, Krasimir Antonov, Tanya Petkova, Evelina Atanasova, Nadezhda Zheleva, Bojidar Tomov, Yana Boyanova, Lyudmila Mateva
Zahariy Krastev, Deian Jelev, Krasimir Antonov, Tanya Petkova, Evelina Atanasova, Nadezhda Zheleva, Bojidar Tomov, Yana Boyanova, Lyudmila Mateva, Clinic of Gastroenterology, University Hospital “St. Ivan Rilski”, 1431 Sofia, Bulgaria
Author contributions: Krastev Z and Mateva L designed the research; Petkova T, Atanasova E, Zheleva N and Boyanova Y collected clinical data; Krastev Z, Jelev D and Antonov K analyzed the data; Tomov B contributed in TACE procedures; Krastev Z, Jelev D, Petkova T and Atanasova E wrote the paper.
Institutional review board statement: 3-D therapy is approved for clinical use in Bulgaria, but in this case was not reimbursed. The Compassionate Use Program of AbbVie was conducted according to the local law and applicable regulatory requirements. The antiviral therapy was personal and was administered after careful medical assessment. Drugs were provided to the patients according to the preliminary approved list by the Bulgarian Drug Agency.
Informed consent statement: Patients provided written informed consent prior to enrollment.
Conflict-of-interest statement: Krastev Z has received fees for serving as a member of the central advisory board of Gilead, as well as research funding from Receptos, Centocor and Millennium Pharmaceuticals; Mateva L has received fees as a local advisory board member of Janssen; Krastev Z, Mateva L, Antonov K and Jelev D have received fees as local advisory board members and/or research fees from Gilead, Abbvie, MSD, Roche, Novartis, Johnson & Johnson, Idenix, Norgine and ACPS - Applied Clinical Pharmacology Services; Krastev Z and Mateva L have received research fees from Comac Medical and Schwabe; Krastev Z, Antonov K and Jelev D have received research funding from GSK; Boyanova Y has received research funding from Norgine, Schwabe and ACPS - Applied Clinical Pharmacology Services.
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: Zahariy Krastev, MD, PhD, DSc (Med), Professor of Medicine, Clinic of Gastroenterology, University Hospital “St. Ivan Rilski”, 15 Acad. Ivan Geshov Blvd, 1431 Sofia, Bulgaria. zahkrastev@gmail.com
Telephone: +359-2-9526319 Fax: +359-2-8510816
Received: August 26, 2015
Peer-review started: August 31, 2015
First decision: September 29, 2015
Revised: October 21, 2015
Accepted: December 12, 2015
Article in press: December 16, 2015
Published online: February 28, 2016
Processing time: 182 Days and 21.6 Hours
Abstract

We observed a sustained viral response (SVR) of ombitasvir/paritaprevir/ritonavir, dasabuvir and ribavirin therapy, for 12 wk, in two cases with compensated liver cirrhosis and fully destroyed early hepatocellular carcinoma (HCC). Patients were infected with hepatitis C virus (HCV) genotype 1b and were previous null responders/relapsers to interferon-alpha/ribavirin (IFN/RBV). There was a rapid suppression of HCV RNA to undetectable levels within the first two treatment weeks. SVR was achieved even after marked reduction of the RBV dose. The treatment was well tolerated. Both subjects experienced worsening of liver disease during therapy, in different patterns: severe, transient, predominantly direct hyperbilirubinemia without cytolysis (case 1) or progressive increase of aminotransferases (grade 4) without severe hyperbilirubinemia (case 2). Adverse events spontaneously resolved. The patients remained in a good clinical condition without hepatic decompensation. There was no re-occurrence of HCC. This is the first report for treatment of HCV cirrhosis after complete HCC destruction.

Keywords: Ombitasvir; Paritaprevir; Ritonavir; Dasabuvir; Ribavirin; Hepatitis C virus cirrhosis; Hepatocellular carcinoma

Core tip: Interferon-free regimens based on a combination of different direct acting antivirals (DAAs) are intensively studied in patients with hepatitis C virus (HCV)-related cirrhosis who are previous null responders or relapsers to interferon/ribavirin. DAAs are very effective and relatively safe in compensated cirrhosis, but there are no data regarding patients with successfully treated hepatocellular carcinoma (HCC). These two cases are the first reports on the efficacy, safety and tolerability of an ombitasvir/paritaprevir/ritonavir plus dasabuvir and ribavirin therapy in subjects with HCV cirrhosis and fully destroyed early HCC, as well as on an evaluation of the serum level of total bile acids during therapy and 12 wk thereafter.