Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death in the world. Infection with hepatitis C virus (HCV) represents one of the most common risk factors for HCC development, and cases of HCV-related complications have been rising over the last 2 decades. Although the standard for HCV therapy has been interferon (IFN)-based for many years, the therapeutic revolution spurred by the development of direct-acting antivirals (DAAs) promises to usher in a new era in which chronic HCV becomes a rare disease. On the basis of long-term follow-up of patients experiencing IFN-based sustained virological responses (SVRs), it can be expected that rates of HCV-associated HCC will decrease significantly after the widespread adoption of DAAs, but there remains a persistent risk for HCC even among some patients with advanced fibrosis who have achieved SVR. As such, individuals treated for HCV with advanced fibrosis should continue to be screened regularly for HCC after SVR. Furthermore, as the population of SVR patients grows, it will become imperative to accurately identify those individuals at high risk for developing HCC, appropriately allocate resources for screening, and consider cost-effective chemopreventive strategies. Risk factors include preexisting advanced fibrosis/cirrhosis, older age, diabetes mellitus, and ethanol use. In addition, laboratory biomarkers and genetic signatures are currently being identified that not only predict the likelihood of HCC development in SVR patients but also may serve as dynamic indicators of therapeutic response.