Metabolic Dysfunction‐Associated Steatotic Liver Disease Increases the Risk of Severe Infection: A Population‐Based Cohort Study

ABSTRACT Background and Aims Metabolic dysfunction‐associated steatotic liver disease (MASLD) is linked to various intrahepatic and extrahepatic diseases, but its association with severe infectious disease remains to be investigated. Methods We analysed data from the Shanghai Suburban Adult Cohort and Biobank, encompassing participants enrolled in 2016 and 2017 with available abdominal ultrasonography data, and followed them up until December 2022 (median follow‐up = 5.71 years). We categorised the participants into the MASLD group and those without steatotic liver disease (non‐SLD). Multivariable‐adjusted Cox regression was used to estimate hazard ratios (HR) for severe infections in patients with MASLD compared to the non‐SLD group. Cumulative incidences were calculated while accounting for competing risks (non‐infection‐related deaths). Mediation analyses were performed to explore the roles of cardiometabolic risk factors in the association between MASLD and severe infections. Results Among the 33 072 eligible participants (mean age 56.37 years; 38.20% male), 11 908 (36.01%) were diagnosed with MASLD at baseline. Severe infections occurred in 912 (7.66%) MASLD patients and 1258 (5.94%) non‐SLD. The rate of severe infections per 1000 person‐years was higher in MASLD patients (13.58) than in comparators (10.48) (fully adjusted HR 1.18, 95% CI 1.07–1.30). The most frequent infections in MASLD were respiratory (7.25/1000 person‐years) and urinary tract infections (2.61/1000 person‐years). The 5‐year cumulative incidence of severe infections was 6.79% (95% CI 6.36–7.26) in MASLD and 5.08% (95% CI 4.79–5.38) in comparators. Cardiometabolic risk factors, including waist circumference, triglycerides and HbA1C, partially mediate the association between MASLD and severe infections. Conclusions Patients with MASLD were at significantly higher risk of incident severe infections compared to the non‐SLD group. Future studies are needed to elucidate the mechanisms linking MASLD to severe infections.