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Gitto et al. Hepatoma Res 2020;6:22 Hepatoma Research
DOI: 10.20517/2394-5079.2019.50

Review Open Access

Direct-acting antivirals and risk of hepatocellular
carcinoma: from genetic signature to metabolic risk
factors

Stefano Gitto , Erica Villa 2
1
1 Department of Experimental and Clinical Medicine, University of Florence, Florence 50121, Italy.
2 Department of Medical Specialties, Gastroenterology Unit, University of Modena & Reggio Emilia, Modena 41124, Italy.

Correspondence to: Prof. Erica Villa, Department of Medical Specialties, Gastroenterology Unit, University of Modena & Reggio
Emilia, Via del Pozzo 71, Modena 41124, Italy. E-mail: erica.villa@unimore.it
How to cite this article: Gitto S, Villa E. Direct-acting antivirals and risk of hepatocellular carcinoma: from genetic signature to
metabolic risk factors. Hepatoma Res 2020;6:22. http://dx.doi.org/10.20517/2394-5079.2019.50
Received: 17 Dec 2019 First Decision: 5 Mar 2020 Revised: 23 Mar 2020 Accepted: 2 Apr 2020 Published: 11 May 2020

Science Editor: Guang-Wen Cao Copy Editor: Jing-Wen Zhang Production Editor: Tian Zhang

Abstract
Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the second leading cause of cancer-
related death. Hepatitis C virus and mainly hepatitis C virus-related cirrhosis is the chief risk factor for HCC. Many
direct-acting antivirals are available for the eradication of hepatitis C virus with remarkable results in terms of
virological response and with optimal safety profile. Notably, some authors have suggested that viral eradication
due to these new drugs might favor both occurrence and recurrence of HCC. The exact biological mechanisms of
carcinogenesis in this specific setting have not been well identified, but it has been suggested that adjustments
in immune surveillance and increase in vascular endothelial growth factor expression could have a chief role.
Remarkably, after publication of many large studies and meta-analyses, we can affirm that there is no increased
risk on a population basis. Nonetheless, on an individual basis, sustained virological response due to direct-acting
antivirals may facilitate HCC onset in some specific subgroups of patients. Among them, we could point out
patients with activated neoangiogenesis but also subjects with particularly severe metabolic imbalance.

Keywords: Direct-acting antivirals, hepatocellular carcinoma, carcinogenesis

INTRODUCTION
[1]
Hepatocellular carcinoma (HCC) represents about 5.6% of cancers worldwide . It is the fifth most common
[2]
malignancy and its incidence has grown in the last two decades . Notably, HCC has a strong impact on
patients’ outcome, being the second leading cause of cancer-related death . Hepatitis C virus (HCV) and
[3]
[4]
particularly HCV-related cirrhosis, is the main risk factor for HCC .

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