Liver cancer risk across metabolic dysfunction-associated steatotic liver disease and/or alcohol: a nationwide study.

ABSTRACT

OBJECTIVES: New terminologies of metabolic dysfunction-associated steatotic liver disease (MASLD) have been developed. We assessed hepatocellular carcinoma (HCC) risk across MASLD and/or alcohol intake. METHODS: We included participants aged 40-79 years receiving a national health check-up from 2009 to 2010 in the Republic of Korea, classified as follows non-MASLD, MASLD, MASLD with increased alcohol intake (MetALD; weekly alcohol 210-420 g for male and 140-350 g for female), and alcohol-associated liver disease (ALD; excessive alcohol intake with weekly alcohol ≥420 g for male or ≥350 g for female). The primary outcome was HCC incidence. HCC risk was estimated using multivariable Cox proportional hazard models. RESULTS: Among 6,412,209 participants, proportions of non-MASLD, MASLD, MetALD, and ALD cases were 59.5%, 32.4%, 4.8%, and 3.4%, respectively. During follow-up (median 13.3 years), 27,118 had newly developed HCC. Compared to non-MASLD, the HCC risk increased from MASLD (adjusted hazard ratio [aHR] 1.66, 95% confidence interval [CI] 1.62-1.71), MetALD (aHR 2.17, 95% CI 2.08-2.27) to ALD (aHR 2.34, 95% CI 2.24-2.45) in a stepwise manner. Furthermore, the older and non-cirrhosis subgroups were more vulnerable to detrimental effect of MASLD and/or alcohol intake, concerning HCC risk. Among the older, female, and cirrhosis subgroups, MetALD poses similar HCC risks as ALD. CONCLUSION: HCC risk increased from MASLD, MetALD to ALD in a stepwise manner, compared to non-MASLD. For an effective primary prevention of HCC, a comprehensive approach should be required to modify both metabolic dysfunction and alcohol intake habit.