RESUMEN
BACKGROUND & AIMS: Better surveillance tests for hepatocellular carcinoma (HCC) are needed. The GALAD score [Gender, Age, AFP-L3, AFP, and Des-carboxy-prothrombin] has been shown to have excellent sensitivity and specificity for HCC in phase two studies. We performed a phase three biomarker validation study to compare GALAD with AFP in detecting HCC. METHODS: This is a prospective study of patients with cirrhosis enrolled at seven centers. Surveillance for HCC was performed every 6 months at each site, and HCC diagnosis was confirmed per AASLD guidelines. Blood for biomarker research was obtained at each follow-up visit and stored in a biorepository. Measurements of AFP, AFP-L3, and DCP (des-gamma carboxyprothrombin) were performed in a FujiFilm laboratory by staff blinded to clinical data. The performance of GALAD in detecting HCC was retrospectively evaluated within 12 months prior to the clinical diagnosis. All analyses were conducted by an unblinded statistician in the EDRN data management and coordinating center. RESULTS: A total of 1,558 patients with cirrhosis were enrolled and followed for a median of 2.2 years. A total of 109 patients developed HCC (76 very early or early stage) with an annual incident rate of 2.4%. The AUC for AFP and GALAD within 12 months prior to HCC 0.66 and 0.78 (p<0.001), respectively. Using cutoff for GALAD of -1.36, the specificity was 82% and sensitivity at 12 months prior to HCC diagnosis was 62%. For comparison, performance of AFP at 82% specificity showed 41% sensitivity at 12 months prior to HCC diagnosis (p=0.001). CONCLUSION: GALAD score, compared to AFP, improves the detection of HCC within 12 months prior to the actual diagnosis.
RESUMEN
BACKGROUND & AIMS: Worldwide, hepatocellular carcinoma (HCC) is a common malignancy. We aimed to prospectively determine the incidence and risk factors of HCC in a U.S. METHODS: The multicenter Hepatocellular Carcinoma Early Detection Strategy study of the National Institutes of Health prospectively enrolled patients with cirrhosis who underwent standard surveillance for HCC. Demographics, medical and family history, etiology of liver disease, and clinical features were evaluated for associations with HCC. RESULTS: Between April 10, 2013 and December 31, 2021, 1723 patients were enrolled and confirmed eligible. During median follow-up of 2.2 years (range, 0-8.7 years), there were 109 incident cases of HCC for an incidence rate of 2.4 per 100 person-years: 88 (81%) patients with very early/early Barcelona Clinic Liver Cancer stage (0, A), 20 (18%) intermediate stage (B), and 1 (1%) unknown stage. Risk factor analyses were restricted to 1325 patients, including 95 incident HCC, with at least 6 months of follow-up. The majority were men (53.2%), obese or severely obese (median body mass index, 30.2 kg/m2), and white (86.3%); 42.0% had history of hepatitis C virus infection, 20.7% had alcoholic liver disease, and 24.9% had nonalcoholic fatty liver disease. Fourteen risk factors for HCC were significant (P < .05) in univariate analyses, and a multivariate subset was selected using stepwise logistic regression. The multivariate subset contained gender (P < .001; male; odds ratio [OR], 2.47; 95% confidence interval [CI], 1.54-4.07), years with cirrhosis (P = .004; OR, 1.06; 95% CI, 1.02-1.1), family history of liver cancer (P = .02; yes; OR, 2.69; 95% CI, 1.11-5.86), age (per 5 years; P = .02; OR, 1.17; 95% CI, 1.03-1.33), obesity (P = .02; yes; OR, 1.7; 95% CI, 1.08-2.73), aspartate aminotransferase (log(1+AST); P = .06; OR, 1.54; 95% CI, 0.97-2.42), alpha-fetoprotein (log(1+AFP); P = .07; OR, 1.32; 95% CI, 0.97-1.77), and albumin (P = .10; OR, 0.7; 95% CI, 0.46-1.07). CONCLUSIONS: Thus far, this is the largest prospective and geographically diverse study of a U.S. cohort of patients with cirrhosis that validates known risk factors for HCC (gender, age, obesity, years with cirrhosis, family history of liver cancer, baseline AFP, albumin, and AST). The incidence of HCC was 2.4% per 100 person-years.