MASLD and MetALD increase the risk of developing hepatocellular carcinoma and incident or decompensated cirrhosis: a Korean nationwide study

Introduction: This study aimed to investigate the liver-related outcomes of newly suggested metabolic dysfunction-associated steatotic liver disease (MASLD) and MASLD with increased alcohol intake (MetALD), as well as alcohol-associated liver disease (ALD). Methods: From a National Health Insurance Service Health Screening Cohort, we included 369,094 participants who underwent health check-ups between 2009 and 2010 in South Korea. SLD was defined as a fatty liver index ≥60. The risk of primary liver cancer (PLCa), hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), incident cirrhosis, and decompensated cirrhosis was compared with no steatotic liver disease (SLD). The subdistribution hazard ratio (SHR) was calculated using the Fine–Gray model regarding competing risks. Results: A total of 3,232 participants (0.9%) developed PLCa during the median follow-up of 3,227,176 person-years: 0.5% with no SLD, 1.1% with MASLD, 1.3% with MetALD, and 1.9% with ALD. Competing risk analysis revealed that compared with no SLD, MASLD (SHR, 1.65; 95% CI, 1.44−1.88), MetALD (SHR, 1.87; 95% CI, 1.52−2.29), and ALD (SHR, 1.86; 95% CI, 1.39−2.49) were associated with an increased risk of PLCa. MASLD (SHR, 1.96; 95% CI, 1.67−2.31), MetALD (SHR, 2.23; 95% CI, 1.75−2.84), and ALD (SHR, 2.34; 95% CI, 1.67−3.29) were associated with a higher risk of HCC. No significant difference was observed in the risk of iCCA. The risk of incident cirrhosis and decompensated cirrhosis increased in the order of no SLD, MASLD, MetALD, and ALD. Conclusion: MASLD, MetALD, and ALD have an increased risk of PLCa, HCC, incident cirrhosis, and decompensated cirrhosis but not iCCA. These findings may serve as a robust ground for the prognostic value of the newly suggested MASLD and MetALD.