Infection Risk in Patients with Biopsy-Proven Fatty Liver Disease: A Cohort Study

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver condition worldwide and is increasingly recognized as a systemic disorder associated with metabolic comorbidities. Whether NAFLD independently increases susceptibility to severe infections remains uncertain, particularly across histological stages of disease. Objective: To determine the incidence and hazard of severe infections among patients with biopsy-confirmed NAFLD compared with matched population controls. Methods: This population-based cohort study included 133 adults with biopsy-proven NAFLD and 629 age- and sex-matched comparators from 1995 to 2017 in Lahore, Pakistan. Patients were stratified by histological severity (simple steatosis, NASH without fibrosis, non-cirrhotic fibrosis, cirrhosis). Severe infections, defined as hospital-diagnosed events requiring systemic therapy or admission, were ascertained through electronic health records. Incidence rates per 1000 person-years were calculated, and Cox proportional hazards models adjusted for demographic and metabolic covariates were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Results: Patients with NAFLD had higher infection rates than controls (17.9 vs 11.3 per 1000 person-years). Adjusted hazards were elevated across infection types, including sepsis (HR 2.16, 95% CI 1.95–2.39), respiratory (HR 1.52, 95% CI 1.42–1.62), and urinary tract infections (HR 1.63, 95% CI 1.51–1.75). Risk increased with histological severity, reaching its highest in cirrhosis (HR 1.37, 95% CI 1.21–1.55). Conclusion: NAFLD was associated with an increased hazard of severe infections, with risk rising across disease stages. Preventive measures and closer surveillance may benefit this population.