Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 28, 2015; 21(12): 3480-3491
Published online Mar 28, 2015. doi: 10.3748/wjg.v21.i12.3480
Hepatitis C virus-specific cytotoxic T cell response restoration after treatment-induced hepatitis C virus control
Juan-Ramón Larrubia, Elia Moreno-Cubero, Joaquín Miquel, Eduardo Sanz-de-Villalobos
Juan-Ramón Larrubia, Elia Moreno-Cubero, Joaquín Miquel, Eduardo Sanz-de-Villalobos, Translational Hepatology Unit, Guadalajara University Hospital, University of Alcalá, 19002 Guadalajara, Spain
Juan-Ramón Larrubia, Eduardo Sanz-de-Villalobos, Department of Medicine and Medical Specialties, University of Alcalá, 28805 Alcalá de Henares (Madrid), Spain
Elia Moreno-Cubero, Department of Biology of Systems, University of Alcalá, 28805 Alcalá de Henares (Madrid), Spain
Author contributions: Larrubia JR and Moreno-Cubero E contributed equally towards the conception and design of the review; Larrubia JR, Moreno-Cubero E, Miquel J, Sanz-de-Villalobos E and Larrubia JR revised the manuscript.
Supported by “Instituto de Salud Carlos III”, Spain and “European Regional Development Fund, a way of making Europe”, E.U. (PI12/00130) and, Moreno-Cubero E was funded by a research award from “Asociación de Hepatología Translacional” (AHT Research Award 2014), Spain.
Conflict-of-interest: The authors declare that there are no conflicts of interest.
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: Juan-Ramón Larrubia, MD, MSc, PhD, Translational Hepatology Unit, Guadalajara University Hospital, University of Alcalá, E-19002 Guadalajara, Spain.
Telephone: +34-949-909200 Fax: +34-949-909256
Received: November 19, 2014
Peer-review started: November 19, 2014
First decision: December 4, 2014
Revised: December 10, 2014
Accepted: February 5, 2015
Article in press: February 5, 2015
Published online: March 28, 2015

Hepatitis C virus (HCV)-specific cytotoxic T cell (CTL) response plays a major role in viral control during spontaneous infection resolution. These cells develop an exhausted and pro-apoptotic status during chronic onset, being unable to get rid of HCV. The role of this response in contributing to sustained viral response (SVR) after anti-HCV is controversial. Recent studies show that after successful interferon-based anti-HCV treatment, HCV traces are still detectable and this correlates with a peak of HCV-specific CTL response activation, probably responsible for maintaining SVR by subsequent complete HCV clearing. Moreover, SVR patients’ serum is still able to induce HCV infection in naïve chimpanzees, suggesting that the infection could be under the control of the immune system after a successful treatment, being transmissible in absence of this adaptive response. At least theoretically, treatment-induced viral load decrease could allow an effective HCV-specific CTL response reestablishment. This effect has been recently described with anti-HCV interferon-free regimes, based on direct-acting antivirals. Nevertheless, this is to some extent controversial with interferon-based therapies, due to the detrimental immunoregulatory α-interferon effect on T cells. Moreover, HCV-specific CTL response features during anti-HCV treatment could be a predictive factor of SVR that could have clinical implications in patient management. In this review, the recent knowledge about the role of HCV-specific CTL response in the development of SVR after anti-HCV treatment is discussed.

Keywords: Hepatitis C virus, Chronic hepatitis, Hepatitis C virus-specific cytotoxic T cell response, Treatment, Direct-acting antivirals, Interferon-alpha, Ribavirin, Exhaustion, Apoptosis

Core tip: Hepatitis C virus (HCV)-specific cytotoxic T lymphocyte (CTL) response plays an essential role in controlling acute HCV infection but its implication in treatment-induced viral control is controversial. During interferon/ribavirin treatment, HCV traces persist after sustained viral response (SVR) and this correlates with an activated HCV-specific CTL response, suggesting the necessity of this response to obtain an indefinite viral control. Current data propose that viral suppression during interferon/ribavirin treatment and during direct-acting anti-viral regimes could affect HCV-specific CTL restoration. Moreover, the features of this CTL response during treatment could have a predictive value on SVR outcome.