Optimal Incidence Threshold for Cost-Effective Hepatocellular Carcinoma Surveillance in Alcohol-Associated Cirrhosis

Current guidelines recommend routine hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis when annual HCC incidence exceeds 1 per 100 person-years, a threshold derived from older studies and not specific to alcohol-associated cirrhosis. However, contemporary data suggest that HCC incidence in this population is often below 1%, leaving the value of routine surveillance uncertain.

We developed a Markov-based state-transition microsimulation model to simulate the natural history of HCC and subsequent treatment pathways in patients with alcohol-associated cirrhosis in the United States setting. The model compared biannual surveillance with ultrasound and alpha-fetoprotein (AFP) versus no surveillance separately for two distinct cohorts: patients who continued to actively consume alcohol and patients who had achieved sustained abstinence. Inputs included the natural history of alcohol-associated cirrhosis, HCC incidence, test performance, surveillance adherence, and contemporary treatment. Sensitivity analyses examined the robustness of model assumptions and findings.

Biannual surveillance becomes cost-effective when annual HCC incidence reached approximately 0.45 per 100 person-years using willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY). Among active drinkers, surveillance yielded an incremental cost-effectiveness ratio (ICER) of $18,952 per QALY; among abstinent patients, the ICER was $56,000 per QALY. Per 100,000 patients, routine surveillance generated an estimated 2,083 additional life-years and 992 QALYs in active drinkers and 3,357 life-years and 1,700 QALYs in abstinent patients.

Routine biannual HCC surveillance with ultrasound and AFP is cost-effective for patients with alcohol-associated cirrhosis in the United States when HCC incidence exceeds 0.45 per 100 person-years, substantially below the historically cited 1 per 100 person-years threshold. Updating clinical guidelines to reflect these contemporary thresholds could improve early HCC detection in this high-risk population.