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Mezzacappa C, Kim NJ, Vutien P, Kaplan DE, Ioannou GN, Taddei TH. Screening for Hepatocellular Carcinoma and Survival in Patients With Cirrhosis After Hepatitis C Virus Cure. JAMA Network Open. 2024 Jul 1; 7(7):e2420963.
IMPORTANCE: The risk of hepatocellular carcinoma (HCC) declines over time after hepatitis C virus (HCV) cure by direct-acting antiviral (DAA) therapies. Liver society guidelines recommend continuing HCC screening for these patients, but data on screening outcomes are lacking. OBJECTIVE: To evaluate the association of HCC screening after HCV cure with overall survival. DESIGN, SETTING, AND PARTICIPANTS: This cohort study evaluated patients with HCV cirrhosis who achieved DAA-induced HCV cure in the Veterans Affairs health care system between January 2014 and December 2022. Data analysis occurred from October 2023 to January 2024. EXPOSURES: The percentage of time spent up to date with recommended HCC screening was calculated by year of follow-up and during the 4 years preceding HCC diagnosis (the detectable asymptomatic phase). MAIN OUTCOMES AND MEASURES: The primary outcome was overall survival after HCC diagnosis and was compared by percentage of time spent up to date with screening using Kaplan-Meier analyses and Cox proportional hazards regression. Early-stage HCC at diagnosis and curative treatment were secondary outcomes assessed using logistic regression. RESULTS: A total of 16 902 individuals were included (median [IQR] age, 64.0 [60.5-67.4] years; 16 426 male [97.2%]), of whom 1622 developed HCC. The cumulative incidence of HCC declined from 2.4% (409 of 16 902 individuals) to 1.0% (27 of 2833 individuals) from year 1 to year 7 of follow-up. Being up to date with screening for at least 50% of time during the 4 years preceding HCC diagnosis was associated with improved overall survival (log-rank test of equality over strata P = .002). In multivariate analysis, each 10% increase in follow-up spent up to date with screening was associated with a 3.2% decrease in the hazard of death (hazard ratio, 0.97; 95% CI, 0.95-0.99). There was a statistically significant interaction between time since HCV cure and screening, with no association observed among those who received a diagnosis of HCC more than 5 years after HCV cure. Each 10% of time spent up to date with screening was associated with a 10.1% increased likelihood of diagnosis with early-stage HCC (95% CI, 6.3%-14.0%) and a 6.8% increased likelihood of curative treatment (95% CI, 2.8%-11.0%). CONCLUSIONS AND RELEVANCE: In this cohort study of persons with HCV-related cirrhosis who achieved HCV cure and subsequently developed HCC, remaining up to date with screening was associated with improved overall survival, supporting the screening of eligible individuals.