AGA Clinical Practice Update on Interaction Between Oral Direct-Acting Antivirals for Chronic Hepatitis C Infection and Hepatocellular Carcinoma: Expert Review

The purpose of this clinical practice update is to evaluate the evidence describing the interaction between direct-acting antiviral (DAA) therapy for hepatitis and hepatocellular carcinoma (HCC) with regard to HCC incidence, HCC recurrence, and DAA efficacy, and to summarize best practice advice regarding HCC surveillance and timing of DAA therapy. The recommendations outlined in this expert review are based on available published evidence, including observational studies and systematic reviews, and incorporates expert opinion where applicable. DAA treatment is associated with a reduction in the risk of incident HCC. The relative risk reduction is similar in patients with and without cirrhosis. Patients with advanced liver fibrosis (F3) or cirrhosis should receive surveillance imaging before initiating DAA treatment. Patients with advanced liver fibrosis (F3) or cirrhosis at the time of DAA treatment represent the highest-risk group for HCC after DAA-induced sustained virologic response. These patients should stay in HCC surveillance. HCC surveillance should be performed using ultrasound with or without α–fetoprotein every 6 months. Current data do not support shorter surveillance intervals or the use of alternative surveillance modalities. Future studies may show a reduction in HCC risk over time after DAA-induced sustained virologic response. However, in the interim, HCC surveillance should continue indefinitely if patients are otherwise eligible for potentially curative therapy. The presence of active HCC is associated with a small but statistically significant decrease in sustained virologic response with DAA therapy. Patients with HCC who are eligible for potentially curative therapy with liver resection or ablation should defer DAA therapy until after HCC treatment is completed. Timing of DAA therapy for patients with HCC who are listed for liver transplantation should be determined with consideration of median wait times, availability of hepatitis C virus–positive organs, and degree of liver dysfunction. There are insufficient data evaluating benefits and cost-effectiveness of DAA therapy in patients with active intermediate or advanced HCC. Decisions regarding DAA treatment in these patients should be considered in light of HCC tumor burden, degree of liver dysfunction, life expectancy, and patient preferences. There are no conclusive data that DAA therapy is associated with increased or decreased risk, differential time to recurrence, or aggressiv