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

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.

Clinical outcomes of direct-acting antiviral therapy in patients with compensated hepatitis C virus-related cirrhosis

“…It is known that the risk of hepatocellular carcinoma increases in advanced stage of fibrosis, in patients with comorbidities such as diabetes mellitus, and in older age [17,18] . The reason why there are different outcomes in terms of cancer development depending on the treatment received could be explained by the fact that patients with more advanced liver disease and with comorbidities are now being treated with direct acting antivirals, as they were not considered suitable for interferon based therapies before due to the possibility of dangerous side effects.…”

Tailored Algorithms for Hepatocellular Carcinoma Surveillance: Is One-Size-Fits-All Strategy Outdated?

“…In addition, the magnitude of HCC risk is not yet completely understood in emerging populations, i.e., non-alcoholic fatty liver disease (NAFLD) without cirrhosis and chronic hepatitis C after viral cure especially by direct-acting antivirals [35–39]. More precise individual HCC risk determination will address the heterogeneous HCC risk among patients and enable optimal allocation of limited resources and capability of HCC surveillance to the subset of patients who have higher risk and may benefit more from regular surveillance.…”

The short‐term incidence of hepatocellular carcinoma is not increased after hepatitis C treatment with direct‐acting antivirals: An ERCHIVES study

“…Hepatocellular carcinoma (HCC) is the second‐leading cause and fastest rising cause of cancer‐related death worldwide . One of the most common risk factors for HCC is cirrhosis attributed to chronic infection with the hepatitis C virus (HCV), which is estimated to infect over 150 million people globally . For decades, the standard of care for HCV treatment had been interferon (IFN)‐based regimens, with approximately 50%‐60% of eligible patients achieving sustained virological response (SVR).…”