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Buonfiglioli et al. Hepatoma Research 2018;4:6 Hepatoma Research
DOI: 10.20517/2394-5079.2017.42

Review Open Access

Direct antiviral therapy for hepatitis C and
hepatocellular carcinoma: facing the conundrum

Federica Buonfiglioli, Stefano Brillanti

Research Center for the Study of Hepatitis, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna
40138, Italy.

Correspondence to: Prof. Stefano Brillanti, Research Center for the Study of Hepatitis, Department of Medical and Surgical Sciences
(DIMEC), University of Bologna, Via Massarenti 9, Bologna 40138, Italy. E-mail: stefano.brillanti@unibo.it
How to cite this article: Buonfiglioli F, Brillanti S. Direct antiviral therapy for hepatitis C and hepatocellular carcinoma: facing the
conundrum. Hepatoma Res 2018;4:6. http://dx.doi.org/10.20517/2394-5079.2017.42
Received: 11 Sep 2017 First Decision: 7 Feb 2018 Revised: 8 Feb 2018 Accepted: 8 Feb 2018 Published: 10 Feb 2018

Science Editor: Guang-Wen Cao Copy Editor: Jun-Yao Li Production Editor: Huan-Liang Wu

Abstract
Direct antiviral therapy has dramatically changed our possibility to eradicate hepatitis C virus (HCV) infection in all
stages of chronic liver disease, with sustained virological response rates well above 90%. HCV eradication should
lead to a better prognosis even after cirrhosis has established, including a reduced risk of developing hepatocellular
carcinoma (HCC). Unfortunately, during the last two years different reports have raised the concern about a possible
increased risk of developing HCC in cirrhotic patients treated with direct antivirals. In this review, we have evaluated the
principal published data and have reached a few conclusions: (1) direct antiviral therapy does not seem to increase the
cumulative annual rate of HCC de novo occurrence or recurrence; (2) direct antiviral therapy seems to accelerate the
development of HCC, soon after the end of treatment, in those patients at higher risk of HCC occurrence or recurrence;
and (3) preliminary reports seem to indicate that HCC developed after direct antiviral therapy has more aggressive
features. These findings clearly indicate the need for aggressive and close monitoring of cirrhotic patients during and
after antiviral treatment, to detect and treat HCC at their earliest occurrence.

Keywords: Direct-acting antivirals, hepatocellular carcinoma, liver cirrhosis, risk, hepatitis C

INTRODUCTION
Hepatocellular carcinoma (HCC) is the fifth most frequent form of cancer worldwide, and it holds the
[1,2]
second place in malignancy-related mortality . Incidence and death rates of HCC are steadily rising in
most parts of the world (about 2%-3% per year).

Chronic hepatitis C is a necro-inflammatory process of the liver, due to hepatitis C virus (HCV) infection,
[3]
that lasts lifelong and progresses to cirrhosis in about 20% of cases . Even if liver cirrhosis per se is not a
© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0 International
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