Incident venous thromboembolism in biopsy-proven metabolic dysfunction-associated steatotic liver disease: a nationwide cohort study

BACKGROUND: The absolute and relative risk of venous thromboembolism (VTE) in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) remains largely unexplored. We conducted a nationwide cohort study to explore this. METHODS: This nationwide, population-based matched cohort study in Sweden included all individuals with biopsy-confirmed MASLD (1965-2017). MASLD was histologically classified into simple steatosis, metabolic dysfunction-associated steatohepatitis (MASH), non-cirrhotic fibrosis, and cirrhosis. Each MASLD case was matched to up to five general population comparators. VTE events were identified using the Swedish National Patient Register up until 2021. RESULTS: We included 11,073 individuals with MASLD and 50,078 comparators. During a median follow-up of 18.6 years., incident VTE occurred in 1,291 patients with MASLD and 4,067 comparators. The incidence rate of VTE was higher in MASLD (7.6 vs. 3.4 per 1,000 person-years), yielding an adjusted hazard ratio (aHR) of 1.78 (95%CI: 1.65-1.91). The absolute risk difference was 3.9 per 1,000 person-years, equating to 1 extra VTE per 26 patients with MASLD over 10 years. MASLD was associated with a higher incidence of VTE triggered by cancer, hospitalization, and surgery. Higher aHRs were observed in women compared to men, and in patients with baseline cancer or metabolic disorders compared to those without. The risk of portal vein thrombosis (PVT) was markedly elevated (aHR=3.40; 95%CI: 2.93-3.95), increasing progressively with MASLD severity (P=0.003). Findings were similar when siblings were used as comparators to account for intrafamilial confounding. CONCLUSIONS: Biopsy-confirmed MASLD was associated with a higher incidence of VTE, particularly PVT.