Assessment of Incidence of and Surveillance Burden for Hepatocellular Carcinoma among Patients with Hepatitis C in the Era of Direct-Acting Antiviral Agents

Importance: In the US, hepatocellular carcinoma (HCC), primarily associated with hepatitis C virus (HCV) infection, is the fastest rising cause of cancer-related death. Wider use of highly effective direct-acting antiviral agents (DAAs) substantially reduces the burden of chronic HCV infection, but the subsequent impacts with HCV-associated HCC remain unknown. Objective: To assess projected changes in the incidence rate of and surveillance burden for HCC in the era of DAA treatment for HCV. Design, Setting, and Participants: This decision analytical model study was performed from January 2019 to February 2020, using an individual-level state-transition simulation model to simulate disease progression, screening, and different waves of antiviral treatments for HCV in the US from 2012 to 2040. Interventions: Current clinical management for chronic HCV infection. Main Outcomes and Measures: Model outcomes were projected temporal trends and age distribution of incident HCC cases and candidates for HCC surveillance among patients with viremia and patients with virologically cured HCV. Results: The simulation model projected that the annual incidence of HCC among patients with viremia and patients with virologically cured HCV will continue increasing to 24000 (95% uncertainty interval [UI], 18000-31000) cases until 2021. In patients with virologically cured HCV, incident HCC cases are projected to increase from 1000 (95% UI, 500-2100) in 2012 to the peak of 7000 (95% UI, 5000-9600) in 2031 with a subsequent decrease to 6000 (95% UI, 4300-8300) by 2040. The proportion of incident HCC cases that occur in individuals with virologically cured HCV is estimated to increase from 5.3% in 2012 to 45.8% in 2040. The number of candidates for HCC surveillance in the population with virologically cured HCV is projected to increase from 106000 (95% UI, 70000-178000) in 2012 to the peak of 649000 (95% UI, 512000-824000) in 2030 and decrease to 539000 (95% UI, 421000-687000) by 2040, while the proportion of all candidates for surveillance who are virologically cured is estimated to increase from 8.5% to 64.6% during the same period. The average age of HCC incidence and surveillance candidates is estimated to increase from 55 in 2012 to 72 and 71, respectively, by 2040. Conclusions and Relevance: The results of this study suggest that the burden of HCC will shift from patients with viremia to patients with virologically cured HCV, and to older populations. Appropriate management may be warranted for early detection of HCC in patients who may no longer be receiving specialty care for liver conditions.