Validation of Texas Hepatocellular Carcinoma Consortium Risk Index in the Hepatocellular Carcinoma Early Detection Strategy Study

Background & Aims We previously developed a hepatocellular carcinoma (HCC) risk stratification model, the Texas HCC Consortium Risk Index (THCC-RI), for patients with cirrhosis. In this cohort study, we aimed to externally validate THCC-RI in a prospective cohort of patients with cirrhosis. Methods We used data from the Hepatocellular Carcinoma Early Detection Strategy (HEDS) Study, a prospective cohort of patients with cirrhosis enrolled in regular HCC surveillance at 7 centers in the United States. Patients were followed from enrollment until HCC diagnosis, liver transplantation, death, or December 2023. Results The analysis was conducted in 1560 patients who contributed a total of 5051 person-years of follow-up (mean age, 59 years; 47% women; 40% with hepatitis C; 16% alcohol-associated disease; and 22% metabolic dysfunction-associated steatotic liver disease). Over a median follow-up of 2.5 years, 114 patients developed HCC. The THCC-RI had a C-index of 0.77 (95% confidence interval [CI], 0.64–0.85), with area under the receiver operating characteristic curve estimates of 0.77 (95% CI, 0.65–0.85) at 1 year, 0.73 (95% CI, 0.66–0.79) at 3 years, and 0.71 (95% CI, 0.65–0.77) at 5 years. THCC-RI was well-calibrated, with good agreement between observed and predicted risk. Compared with the medium-risk group (deciles 3–8), the high-risk group (deciles 9, 10) had 3.5-fold (hazard ratio, 3.5; 95% CI, 2.4–5.1) higher risk of HCC. THCC-RI had similar discrimination as the Age, Male, Albumin-bilirubin, and Platelets (aMAP) score during the first 2 years of follow-up, but the areas under the receiver operating characteristic curve for aMAP dropped more than those for THCC-RI as the time horizon expanded beyond 3 years. Conclusions In an independent multi-center cohort, THCC-RI had good performance for predicting the future risk of HCC in patients with cirrhosis, with stable discrimination and calibration over a 5-year follow-up. Implementation of THCC-RI into clinical care pathways requires further research.