Case Report
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jul 18, 2016; 8(20): 858-862
Published online Jul 18, 2016. doi: 10.4254/wjh.v8.i20.858
Hepatitis C virus cures after direct acting antiviral-related drug-induced liver injury: Case report
Yaakov Hasin, Shimon Shteingart, Harel Dahari, Inna Gafanovich, Sharon Floru, Marius Braun, Amir Shlomai, Anthony Verstandig, Ilana Dery, Susan L Uprichard, Scott J Cotler, Yoav Lurie
Yaakov Hasin, Shimon Shteingart, Inna Gafanovich, Ilana Dery, Yoav Luria, Liver Unit, Digestive Disease Institute, Shaare Zedek Medical Center, Jerusalem 9103102, Israel
Harel Dahari, Susan L Uprichard, Scott J Cotler, the Program for Experimental and Theoretical Modeling, Division of Hepatology, Department of Medicine, Loyola University Medical Center, Maywood, IL 60153, United States
Sharon Floru, “Bat Yamon” Internal Medicine Day Care, Clalit Health Care Organization, Bat Yam 5962025, Israel
Marius Braun, Amir shlomai, Liver Institute, Rabin Medical Center, Beilinson Hospital, Petah-Tiqwa, Affiliated with the Sackler Faculty of Medicine, Tel Aviv 4941492, Israel
Anthony Verstandig, Invasive Radiology Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel
Author contributions: All authors contributed to the acquisition of data, writing, and revision of this manuscript.
Supported by NIH, No. R01-AI078881.
Institutional review board statement: This case report was exempt from the Institutional Review Board standards and from informed consent by the institutional review board in “Shaare Zedek” medical center.
Informed consent statement: This case report was exempt from providing informed consent by the institutional review board in “Shaare Zedek” medical center.
Conflict-of-interest statement: All the authors have no conflicts of interests to declare.
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:
Correspondence to: Dr. Yoav Luria, Liver Unit, Digestive Disease Institute, Shaare Zedek Medical Center, Shmu’el Bait St 12, Jerusalem 9103102, Israel.
Telephone: +972-2-6555035 Fax: +972-2-6555359
Received: February 28, 2016
Peer-review started: February 29, 2016
First decision: April 15, 2016
Revised: June 1, 2016
Accepted: June 27, 2016
Article in press: June 29, 2016
Published online: July 18, 2016

The United States Food and Drug Administration recently warned that the direct acting antiviral (DAA) combination hepatitis C virus (HCV) treatment of Paritaprevir, Ombitasvir, Dasabuvir, Ritonavir, and Ribavirin (PODr + R) can cause severe liver injury in patients with advanced liver disease. Drug induced liver injury was observed in a small number of patients with decompensated cirrhosis treated with other DAAs, but has not been reported in patients with compensated cirrhosis. We report a case of a 74-year-old woman with chronic HCV and Child-Pugh class A cirrhosis (compensated cirrhosis) treated with PODr + R. The patient presented on day 14 of PODr + R therapy with jaundice and new-onset ascites. Her total bilirubin level increased to 23 mg/dL and international normalized ratio rose to 1.65, while aminotransferase levels remained relatively stable. Hepatitis C treatment was discontinued on day 24 and she gradually recovered. Follow-up testing showed that she achieved a sustained virologic response. In conclusion, hepatic decompensation developed within two weeks of starting treatment with PODr + R in a patient with Child-Pugh class A cirrhosis and was characterized by jaundice and ascites with stable aminotransferase levels. Careful monitoring is warranted in patients with HCV-related cirrhosis treated with PODr + R.

Keywords: Direct antiviral agent, Drug-induced liver injury, Hepatitis C, Mathematical modeling, Sustained virological response, Viral kinetics

Core tip: To the best of our knowledge, this is the first report of hepatic decompensation in a hepatitis C patient with Child Pugh class A cirrhosis due to treatment with Paritaprevir, Ombitasvir, Dasabuvir, Ritonavir and Ribavirin (PODr + R). Liver aminotransferase levels did not increase prior to decompensation, depriving us of our usual alarm signs heralding hepatic decompensation. The patient achieved sustained virologic response despite very early discontinuation of therapy (day 24).