Is hepatocellular carcinoma risk impacted favorably or unfavorably by hepatitis C virus therapy with direct‐acting antivirals?

Cirrhosis is the strongest risk factor for hepatocellular carcinoma (HCC), with hepatitis C virus (HCV) being a major risk factor in the Western world and Japan. The advent of the new direct-acting antivirals (DAAs) revolutionized the treatment of HCV infection, with very high rates of sustained virologic response, very few contraindications, and low rate of adverse events. Hypothetically involved mechanisms regarding higher risk of HCC after DAA therapy focused on a loss of immune control owing to clearance of HCV-specific T-cells from the liver. The chapter aims to emulate a randomized trial using observational data and to establish a comparable index time for DAA-untreated patients. Studies showed that DAA treatment could improve liver function, reduce risk of decompensation, and reduce waitlist dropout due to HCC progression or death.