The FMO score stratifies hepatocellular carcinoma risk in individuals with obesity: a nationwide cohort study

Abstract The fibrotic/at-risk MASH in obesity (FMO) score, comprising four routine biochemical parameters, noninvasively identifies individuals with obesity at risk for metabolic dysfunction-associated steatohepatitis (MASH). Although it predicts composite liver-related outcomes, whether it stratifies hepatocellular carcinoma (HCC) risk remains unknown. Using the Japan Medical Data Center claims database (2007–2024), we evaluated 1,336,229 individuals with obesity, stratified into rule-out (FMO ≤ 0.05), indeterminate-risk (0.05 < FMO < 0.22), and rule-in (FMO ≥ 0.22) zones. During a median follow-up of 3.7 years, 693 HCC events occurred, with incidence rates of 0.091, 0.168, and 0.260 per 1,000 person-years across zones. Compared with rule-out, the rule-in zone was significantly associated with HCC in univariate (hazard ratio, 2.850; 95% CI, 2.328–3.489) and multivariate analyses (adjusted hazard ratio [aHR], 1.783; 95% CI, 1.409–2.257). The indeterminate-risk zone also showed elevated risk (aHR, 1.446; 95% CI, 1.206–1.732; all p < 0.001). Associations were consistent across all predefined subgroups. Among over 1.3 million individuals with obesity, the FMO score showed substantial utility for HCC risk stratification. Derived from routine metabolic parameters, it might help identify individuals at elevated HCC risk warranting enhanced surveillance. Word count: 187 words.