Hepatitis C-related hepatocellular carcinoma in the era of new generation antivirals

Thomas F Baumert, Frank Jühling, Atsushi Ono, Yujin Hoshida, Thomas F Baumert, Frank Jühling, Atsushi Ono, Yujin Hoshida

Abstract

Hepatitis C virus infection is a major cause of hepatocellular carcinoma worldwide. Interferon has been the major antiviral treatment, yielding viral clearance in approximately half of patients. New direct-acting antivirals substantially improved the cure rate to above 90%. However, access to therapies remains limited due to the high costs and under-diagnosis of infection in specific subpopulations, e.g., baby boomers, inmates, and injection drug users, and therefore, hepatocellular carcinoma incidence is predicted to increase in the next decades even in high-resource countries. Moreover, cancer risk persists even after 10 years of viral cure, and thus a clinical strategy for its monitoring is urgently needed. Several risk-predictive host factors, e.g., advanced liver fibrosis, older age, accompanying metabolic diseases such as diabetes, persisting hepatic inflammation, and elevated alpha-fetoprotein, as well as viral factors, e.g., core protein variants and genotype 3, have been reported. Indeed, a molecular signature in the liver has been associated with cancer risk even after viral cure. Direct-acting antivirals may affect cancer development and recurrence, which needs to be determined in further investigation.

Keywords: Direct-acting antivirals; Hepatitis C virus; Hepatocellular carcinoma; Interferon; Sustained virologic response.

Figures

Fig. 1
Fig. 1
Natural history of HCV-related HCC development and modulation by anti-HCV therapies. Progressive liver fibrosis along with aging gradually increases the risk of hepatocarcinogenesis, which could be further accelerated by several host and viral risk factors. Annual incidences of HCC development and recurrence after DAA-based SVR were estimated from retrospective and prospective studies summarized in Table 1. SVR induced by interferon- or DAA-based anti-HCV therapies may result in distinct post-SVR HCC risk. AFP alpha-fetoprotein, DAA direct-acting antiviral, HCV hepatitis C virus, HCC hepatocellular carcinoma, SVR sustained virologic response

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