Abstract
Direct-acting antivirals (DAAs) induce a rapid virologic response (SVR) in up to 99% of chronic hepatitis C patients. The role of SVR by DAAs on the incidence or recurrence of hepatocellular carcinoma (HCC) is still a matter of debate, although it is known that SVR does not eliminate the risk of HCC. In this review, we made an updated analysis of the literature data on the impact of SVR by DAAs on the risk of HCC as well as an assessment of risk factors and the role of epigenetics. Data showed that SVR has no impact on the occurrence of HCC in the short–medium term but reduces the risk of HCC in the medium–long term. A direct role of DAAs in the development of HCC has not been demonstrated, while the hypothesis of a reduction in immune surveillance in response to the rapid clearance of HCV and changes in the cytokine pattern influencing early carcinogenesis remains to be further elucidated. HCV induces epigenetic alterations such as modifications of the histone tail and DNA methylation, which are risk factors for HCC, and such changes are maintained after HCV clearance. Future epigenetic studies could lead to identify useful biomarkers and therapeutic targets. Cirrhosis has been identified as a risk factor for HCC, particularly if associated with high liver stiffness and α-fetoprotein values, diabetes and the male sex. Currently, considering the high number and health cost to follow subjects’ post-HCV clearance by DAAs, it is mandatory to identify those at high risk of HCC to optimize management.
Highlights
Treatment based on direct-acting antivirals (DAAs) has radically changed the natural history of chronic hepatitis C virus (HCV) infection [1]
The results of this study showed changes in H3K27ac in the liver tissue of chronic HCV patients and that these changes were still present after HCV clearance by either Direct-acting antivirals (DAAs) or IFN, suggesting that epigenetic alterations caused by HCV persisted after the virus elimination [96]
In a large multicenter study that included 1675 HCV patients followed for 17 months post-treatment with DAAs, it was shown that the 1-year cumulative rates of hepatocellular carcinoma (HCC) recurrence were 6.5% and 23.1% for the non-cirrhosis and cirrhosis patients, respectively, and cirrhosis was identified as a risk predictor of HCC [100]
Summary
Treatment based on direct-acting antivirals (DAAs) has radically changed the natural history of chronic hepatitis C virus (HCV) infection [1]. HCV clearance by DAAs and the consequent reduction in the hepatic necro-inflammation activity should reduce the risk of developing HCC. Several long-term studies in HCV patients treated with IFN-based regimens have documented a reduction in the incidence of HCC by 75% in patients with SVR and a residual risk of the development of HCC mainly associated with some comorbidities such as metabolic syndrome and diabetes mellitus [20,21,22,23]. The purpose of this review is to analyze the published data on the incidence or recurrence of HCC and on the associated risk factors in patients with chronic HCV infection treated with DAAs and SVR, in order to gather an updated overview of the available scientific evidence on such a debated topic.
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