Hepatitis C virus-associated hepatocellular carcinoma after sustained virologic response

Abstract

The introduction of a direct-acting antiviral (DAA) for patients with hepatitis C virus (HCV) infection, could lead to higher sustained virologic response (SVR) rates with fewer adverse events, and it could shorten the treatment duration relative to the interferon era. Although most recent clinical studies have demonstrated that the occurrence rates of hepatocellular carcinoma (HCC) are decreased by SVR with both interferon-based and interferon-free-regimens, there are several reports about the unexpected observation of high rates of early tumor occurrence and recurrence in patients with HCV-related HCC undergoing interferon-free therapy despite SVR. Several mechanisms of HCC occurrence and rapid immunological changes, including cytokines and chemokines during and after DAA treatment, have also been reported. We focused on the possibilities that HCC occurs or recurs during and after DAA treatment, based on the reported clinical and basic studies. Further studies and observations will be needed to determine the short-term and long-term effects on hepatocarcinogenesis caused by the eradication of HCV with DAAs. New serum biomarkers and a follow-up system for HCV-patients with SVR should be established.

Molecular Mechanisms Driving Progression of Liver Cirrhosis towards Hepatocellular Carcinoma in Chronic Hepatitis B and C Infections: A Review

“…Additionally, ~70% of HCC cases are caused by HBV and/or HCV infection. Although nucleos(t)ide analogs and direct-acting antivirals can control HBV and HCV replication, HCC occurrence is occasionally observed [49,50,51], and better biomarkers for early detection of HCC are needed. Furthermore, genetic and epigenetic factors, such as miRs, are involved in liver cirrhosis and its progression to HCC.…”

“…Additionally, HBsAg-positive HCV-coinfected patients with liver cirrhosis are at a high risk of developing HCC [45], with elevated ALT levels [46] and hepatic steatosis [47] risk factors for the development of HCC in patients with HCV-related liver cirrhosis. SVR can reduce HCC development in most patients infected with HCV-related liver cirrhosis [48], although changes in the risk of HCC development following HCV eradication with direct-acting antivirals (DAAs) is controversial [49,50,51]. Further studies will be needed in DAA-era.…”

A Study of Hepatocellular Carcinoma in Chronic Hepatitis C Patients Received Direct Acting Antiviral Drugs

“…On the other hand, the study of Yoo et al 12 on 574 HCV patients receiving direct-acting antiviral therapy for at least 24 weeks, found that the cumulative HCC incidence was 0.47%. Unfortunately, these two studies didn't report the percentage of cirrhosis patients according to the Metavirscore.Multiple mechanisms for the occurrence of HCC and rapid immune changes have also been documented, includes cytokines and chemokines during and following DAA therapy 13 .…”

Before Direct-Acting Antivirals for Hepatitis C Virus: Evaluation of Core Protein R70Q and L/C91M Substitutions in Chronically Infected Brazilian Patients Unresponsive to IFN and/or RBV

“…Patients with advanced stages of liver damage caused by the infectious inflammatory HCV processes may continue to present an important risk for progression of the fibrotic condition and development of HCC, even after clearance of the viral infection. SVR can reduce the risk of developing HCC in most patients with HCV-related liver cirrhosis; however, some studies have reported an increased and recurrent rate of HCC in patients with HCV cirrhosis who had been treated with DAAs [ 39 , 40 , 41 ]. The mechanisms underlying these events are not fully understood [ 42 ].…”