Risk of Hepatocellular Carcinoma by Steatotic Liver Disease and Its Newly Proposed Subclassification

Abstract

Introduction: Steatotic liver disease (SLD) is a new overarching term proposed to replace nonalcoholic fatty liver disease and metabolic dysfunction-associated fatty liver disease. Subclassification includes metabolic dysfunction-associated SLD (MASLD), MASLD with increased alcohol intake (MetALD), and cryptogenic SLD. This study aimed to investigate whether SLD and its subclassification could stratify hepatocellular carcinoma (HCC) risk.

Methods: A cohort of 85,119 adults without viral hepatitis or heavy alcohol intake was analyzed for the risk of HCC according to SLD and its subclassification. The fibrosis-4 (FIB-4) index was used to estimate the degree of liver fibrosis.

Results: During a median follow-up of 11.9 years, HCC was diagnosed in 123 individuals. The incidence rate of HCC per 1,000 person-years was higher in individuals with SLD than in those without SLD (0.197 vs. 0.071, p < 0.001), with an adjusted hazard ratio of 2.02 (95% confidence interval: 1.40-2.92). The HCC incidence rate per 1,000 person-years was 0, 0.180, and 0.648 for cryptogenic SLD, MASLD, and MetALD, respectively. When participants with SLD was further stratified by the FIB-4 index, the HCC incidence rate per 1,000 person-years was 0.074 for SLD with FIB-4 < 1.3 and 0.673 for SLD with FIB-4 ≥ 1.3. Of note, HCC risk was substantially high (HCC incidence rate: 1.847 per 1,000 person-years) for MetALD with FIB-4 ≥ 1.3.

Conclusions: HCC risk was different by SLD and its subclassification. The utilization of SLD and its subclassification can aid in stratifying HCC risk and facilitate the identification of individuals requiring interventions to mitigate the risk of HCC.

Keywords: Hepatocellular carcinoma; Metabolic dysfunction-associated fatty liver disease; Metabolic dysfunction-associated steatotic liver disease; Nonalcoholic fatty liver disease; Steatotic liver disease.

Fig. 1.

Patient flow.

Fig. 2.

Risk of HCC according to the presence of SLD and its subclassification. Comparison performed with the log-rank test. HCC, hepatocellular carcinoma; SLD, steatotic liver disease; MASLD, metabolic dysfunction-associated steatotic liver disease; MetALD, MASLD with increased alcohol intake. * The analysis excluded 25 individuals who did not fit into any SLD subclassification, characterized as having SLD and increased alcohol intake, but without metabolic syndrome.

Fig. 3.

Risk of HCC according to the severity of SLD. Comparison performed with the log-rank test. HCC, hepatocellular carcinoma; SLD, steatotic liver disease; FIB-4, fibrosis-4.

Fig. 4.

Proportion of those with advanced fibrosis among individuals with SLD subclassification. SLD, steatotic liver disease; MASLD, metabolic dysfunction-associated steatotic liver disease; MetALD, MASLD with increased alcohol intake; FIB-4, fibrosis-4.