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World J Gastroenterol. Jun 28, 2018; 24(24): 2582-2595
Published online Jun 28, 2018. doi: 10.3748/wjg.v24.i24.2582
Direct-acting antivirals and hepatocellular carcinoma in chronic hepatitis C: A few lights and many shadows
Maria Guarino, Anna Sessa, Valentina Cossiga, Federica Morando, Nicola Caporaso, Filomena Morisco, On behalf of the Special Interest Group on “Hepatocellular carcinoma and new anti-HCV therapies” of the Italian Association for the Study of the Liver
Maria Guarino, Anna Sessa, Valentina Cossiga, Federica Morando, Nicola Caporaso, Filomena Morisco, Gastroenterology Unit, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
Author contributions: All authors equally contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.
Conflict-of-interest statement: None of the authors had personal or financial conflict 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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Nicola Caporaso, MD, Full Professor, Gastroenterology Unit, Department of Clinical Medicine and Surgery, University of Naples “Federico II”, Via S. Pansini5, Naples 80131, Italy. nicola.caporaso@unina.it
Telephone: +39-08-17462761 Fax: +39-08-17464746
Received: April 19, 2018
Peer-review started: April 21, 2018
First decision: May 9, 2018
Revised: May 18, 2018
Accepted: June 9, 2018
Article in press: June 12, 2018
Published online: June 28, 2018
Abstract

With the introduction of direct-acting antiviral agents (DAA), the rate of sustained virological response (SVR) in the treatment of hepatitis C virus (HCV) has radically improved to over 95%. Robust scientific evidence supports a beneficial role of SVR after interferon therapy in the progression of cirrhosis, resulting in a decreased incidence of hepatocellular carcinoma (HCC). However, a debate on the impact of DAAs on the development of HCC is ongoing. This review aimed to analyse the scientific literature regarding the risk of HCC in terms of its recurrence and occurrence after the use of DAAs to eradicate HCV infection. Among 11 studies examining HCC occurrence, the de novo incidence rate ranged from 0 to 7.4% (maximum follow-up: 18 mo). Among 18 studies regarding HCC recurrence, the rate ranged from 0 to 54.4% (maximum “not well-defined” follow-up: 32 mo). This review highlights the major difficulties in interpreting data and reconciling the results of the included studies. These difficulties include heterogeneous cohorts, potential misclassifications of HCC prior to DAA therapy, the absence of an adequate control group, short follow-up times and different kinds of follow-up. Moreover, no clinical feature-based scoring system accounts for the molecular characteristics and pathobiology of the tumours. Nonetheless, this review does not suggest that there is a higher rate of de novo HCC occurrence or recurrence after DAA therapy in patients with previous HCV infection.

Keywords: Hepatocellular carcinoma, Hepatitis C virus, Direct-acting antiviral agents, Occurrence, Recurrence

Core tip: A significant debate about the impact of direct-acting antiviral agents (DAAs) on the development of hepatocellular carcinoma (HCC) is currently ongoing. After a full review of the published literature, the evidence does not suggest that there is a higher rate of de novo HCC occurrence or recurrence after DAA therapy in patients with previous hepatitis C virus infection.