Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 28, 2017; 23(24): 4317-4323
Published online Jun 28, 2017. doi: 10.3748/wjg.v23.i24.4317
Risk of hepatitis B reactivation in patients treated with direct-acting antivirals for hepatitis C
Ioanna Aggeletopoulou, Christos Konstantakis, Spilios Manolakopoulos, Christos Triantos
Ioanna Aggeletopoulou, Christos Konstantakis, Christos Triantos, Department of Gastroenterology, University Hospital of Patras, 26504 Patras, Greece
Spilios Manolakopoulos, 2nd Department of Internal Medicine, Hippokration General Hospital of Athens, 11527 Athens, Greece
Author contributions: Aggeletopoulou I collection data and drafting the manuscript; Konstantakis C collection data; Manolakopoulos S interpretation of the data, drafting the manuscript, and revision of manuscript for important intellectual content; Triantos C interpretation of the data, drafting the manuscript, and revision of manuscript for important intellectual content
Conflict-of-interest statement: Spilios Manolakopoulos has received research grants from Gilead Sciences and Bristol-Myers Squibb and fees for lectures and being an advisory board member from Gilead Sciences, Bristol-Myers Squibb, Janssen, AbbVie and MSD. Christos Triantos has received fees as a speaker/advisory board member and research/travel grants from MSD, Roche, AbbVie, Janssen, Bristol-Myers Squibb, Bayer and Gilead Sciences.
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: Christos Triantos, MD, Department of Gastroenterology, University Hospital of Patras, D. Stamatopoulou 4, Rio 26504, Patras, Greece. chtriantos@hotmail.com
Telephone: +30-697-2894651 Fax: +30-261-0625382
Received: January 27, 2017
Peer-review started: February 4, 2017
First decision: February 27, 2017
Revised: March 28, 2017
Accepted: May 9, 2017
Article in press: May 9, 2017
Published online: June 28, 2017
Processing time: 150 Days and 3.5 Hours

The recent introduction of direct-acting antiviral drugs (DAAs) for treatment of the hepatitis C virus (HCV) has greatly improved the management of HCV for infected patients. These viral protein inhibitors act rapidly, allowing HCV clearance and increasing the sustained virological response rates. However, hepatitis B virus (HBV) reactivation has been reported in HCV/HBV co-infected patients. Hepatitis B reactivation refers to an abrupt increase in the HBV and is well-documented in patients with previously undetected HBV DNA due to inactive or resolved HBV infection. Reactivation can occur spontaneously, but in most cases, it is triggered by various factors. Reactivation can be transient, without clinical symptoms; however, it usually causes a hepatitis flare. HBV reactivation may occur regardless of HCV genotype and type of DAA regimen. HBV screening is strongly recommended for co-infected HCV/HBV patients before initiation and during DAA therapy regardless of HBV status, HCV genotype and class of DAAs used. HBV reactivation can be prevented with pretreatment screening and prophylactic treatment when necessary. Additional data are required to evaluate the underlying mechanisms of HBV reactivation in this setting.

Keywords: Hepatitis B, Hepatitis C, Hepatitis B virus reactivation, Direct-acting antivirals, Pretreatment screening

Core tip: Hepatitis B reactivation is related to an abrupt increase in hepatitis B virus (HBV) replication in patients with inactive or resolved hepatitis B. Most cases of HBV reactivation resolve spontaneously, but the existence of continuous immune suppression leads to hepatitis flare development and then to progressive acute hepatic injury. The introduction of direct-acting antiviral drugs (DAAs) treatment increases the risk of HBV reactivation in hepatitis C virus (HCV) /HBV co-infected patients. The high incidence of HBV reactivation in these patients highlights the necessity for HBV pretreatment screening before initiation and during DAA therapy.