Abstract
Despite the success of direct-acting antiviral (DAA) agents in treating chronic hepatitis C virus (HCV) infection, the number of cases of HCV-related hepatocellular carcinoma (HCC) is expected to increase over the next five years. HCC develops over the span of decades and is closely associated with fibrosis stage. HCV both directly and indirectly establishes a pro-inflammatory environment favorable for viral replication. Repeated cycles of cell death and regeneration lead to genomic instability and loss of cell cycle control. DAA therapy offers >90% sustained virological response (SVR) rates with fewer side effects and restrictions than interferon. While elimination of HCV helps to restore liver function and reverse mild fibrosis, post-SVR patients remain at elevated risk of HCC. A series of studies reporting higher than expected rates of HCC development among DAA-treated patients ignited debate over whether use of DAAs elevates HCC risk compared to interferon. However, recent prospective and retrospective studies based on larger patient cohorts have found no significant difference in risk between DAA and interferon therapy once other factors are taken into account. Although many mechanisms and pathways involved in hepatocarcinogenesis have been elucidated, our understanding of drivers specific to post-SVR hepatocarcinogenesis is still limited, and lack of suitable in vivo and in vitro experimental systems has hampered efforts to examine etiology-specific mechanisms that might serve to answer this question more thoroughly. Further research is needed to identify risk factors and biomarkers for post-SVR HCC and to develop targeted therapies based on more complete understanding of the molecules and pathways implicated in hepatocarcinogenesis.
Highlights
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer as well as the fastest growing cause of cancer-related mortality worldwide [1]
Patients with chronic hepatitis C virus (HCV) should be treated as early as possible to reduce the risk of HCC, but even successful clearance of the virus may not prevent progression to HCC, and HCC may develop in some patients up to 10 years after sustained virological response (SVR)
In a large retrospective cohort study of more than 10,000 patients who achieved SVR, among whom 100 developed HCC, El-Serag found that HCC risk is significantly reduced following SVR, but the authors caution that the risk remains relatively high (0.33%), among patients with cirrhosis, diabetes, or genotype 3 infection and in patients older than 64 [40,46]
Summary
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer as well as the fastest growing cause of cancer-related mortality worldwide [1]. Up to 850,000 new cases are diagnosed each year, and this number is expected to grow, especially in hepatitis B virus (HBV)-endemic regions, including sub-Saharan. While HBV vaccination has reduced the number of new infections, there remains no curative treatment for chronic HBV, greatly increasing the risk of HCC in these patients. Hepatitis C virus (HCV) infection is the leading cause of HCC in developed countries and is responsible for the recent overall rise in HCC cases [2,3,4]. Patients with chronic HCV should be treated as early as possible to reduce the risk of HCC, but even successful clearance of the virus may not prevent progression to HCC, and HCC may develop in some patients up to 10 years after SVR
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
