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Pazgan-Simon. Hepatoma Res 2020;6:17 I http://dx.doi.org/10.20517/2394-5079.2019.52 Page 3 of 8

Table 1. Risk factors of HCC development in patients treated with interferon depending on the time since the end of treatment
Up to 2 years following the end of treatment Up to 4 years following the end of treatment Over 4 years following the end of treatment
Older age Older age Diabetes
Male sex Diabetes
Advanced fibrosis Advanced fibrosis
Fatty liver disease Elevated AFP levels
Elevated AFP level at the end of treatment
HCC: hepatocellular carcinoma

INTERFERON TREATMENTS
In the 1980s, natural interferon was approved for the treatment of HCV infection, followed by alpha-2a and
2b interferon, and pegylated alpha-2a and alpha-2b interferon approved in 2002. These were administered
subcutaneously, offering the efficacy below 50%, even when administered in combination with ribavirin,
with peginterferons being the most effective. The treatment was associated with numerous adverse effects,
frequently causing premature drug discontinuation. However, apart from their antiviral effect, interferons
also exerted antifibrotic and antineoplastic effect. Interferon therapy could not be used in some patients and
was only limited to those with non-advanced liver disease, without numerous contraindications for the use
of interferon alpha.

The natural course of HCV infection may lead to the development of HCC in some cases [Table 1]. The risk
of HCC development in patients with cirrhosis (CTP A) treated with interferon was lower in responders
(SVR achieved) than in non-responders.

INTERFERON-FREE TREATMENTS
The first interferon-free treatment of HCV infection, sofosbuvir, was approved in 2014. It quickly became
clear that due to virus variation, monotherapy was ineffective. When combined therapy with direct acting
antivirals (DAA), different targets had to be used. The currently available interferon-free treatments are
effective in the majority (over 95%) of patients, regardless of their age, sex, ethnicity, body weight, liver
disease stage or co-infection with HIV.

DAA medications act on known HCV replication targets, effectively leading to a complete virion elimination.
The agents currently used include a pangenotypic combination of (1) sofosbuvir (NS5B polymerase
inhibitor)/velpatasvir (NS5A inhibitor) with or without voxilaprevir (NS3/4A inhibitor); (2) ombitasvir
(NS5A inhibitor)/paritaprevir (NS3/4A inhibitor) - ritonavir with or without dasabuvir (non-nucleotide
NS5A inhibitor), glecaprevir NS3/4A inhibitor/pibrentasvir (NS5A inhibitor); and (3) grazoprevir (NS3/4A
[7,8]
protease inhibitor)/elbasvir (NS5A inhibitor), which is effective in genotype 1 and 4 HCV infection .

EASL AND AASLD RECOMMENDATIONS FOR THE MANAGEMENT OF PATIENTS WITH HCV
AND HCC
EASL guidelines advise against declining antiviral therapy in patients with cirrhosis, including advanced
cirrhosis. However, continued surveillance is still required following successful antiviral therapy. The risk
of HCC for patients with HCV-related cirrhosis who develop SVR after DAA treatment is lowered, but not
eliminated.

Whilst direct-acting antiviral therapies definitely improve survival in patients with cirrhosis previously
treated for HCC, the impact of HCV eradication by DAAs on the future risk of HCC is uncertain. Therefore,
patients with HCV-related cirrhosis and history of HCC should be considered for treatment with DAAs but
should also continue to undergo surveillance.