Association between steatotic liver disease and risk of incident systemic sclerosis: a nationwide cohort study

Abstract

Objective Antinuclear antibody (ANA) positivity has been observed in patients with steatotic liver disease (SLD); however, the link between SLD and ANA-positive connective tissue diseases remains unexplored. We aimed to evaluate the association between SLD and risk of systemic sclerosis (SSc), a representative ANA-positive connective tissue disease. Methods A longitudinal population-based cohort study using a Korean nationwide database was conducted. The analysis included 4,413 719 individuals who participated in a national health screening program in 2012, with a mean follow-up period of 9.21 ± 1.05 years. Participants were categorized based on SLD status into four groups: no SLD, metabolic dysfunction-associated liver disease (MASLD), metabolic dysfunction and alcohol-related liver disease (MetALD), and alcohol-related liver disease (ALD). The main outcome measure was incident SSc. Multivariable Cox proportional hazard models were used to evaluate the association between SLD and risk of incident SSc. Results Among the 4,413 719 individuals, 2,827 907 (64.07%) had no SLD, 1,344 494 (30.46%) had MASLD, 165 475 (3.75%) had MetALD, and 75 843 (1.72%) had ALD. Compared with individuals without SLD, those with MASLD (adjusted hazard ratio [HR]: 1.612 [1.276, 2.038]), MetALD (adjusted HR: 1.575 [0.816, 3.040]), and ALD (adjusted HR: 3.063 [1.635, 5.739]) had a higher risk of incident SSc, with MASLD and ALD reaching statistical significance. The risk was the highest among individuals with ALD. Conclusion SLD was linked to an increased risk of incident SSc. These findings underscore the need for effective monitoring and management of SLD, particularly by reducing excessive alcohol consumption, to lower the risk of incident SSc.