Author information

¹Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.

²Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

³Department of Gastroenterology and Hepatology, University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland.

⁴Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.

⁵Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA.

⁶Division of Hepatology, Department of Upper GI, Karolinska University Hospital, Stockholm, Sweden.

Abstract

Background and aims: Previous literature suggests an association between non-alcoholic fatty liver disease (NAFLD) and infections. We aimed to determine the rate and risk of severe infections in NAFLD compared to the general population.

Methods: In this population-based cohort study, we used national registers to identify all patients with a hospital-based diagnosis of NAFLD in Sweden 1987-2020 (n = 14 869). The patients were matched with ≤10 comparators from the general population for age, sex, municipality, and calendar year (n = 137 145). Cox regression was used to estimate hazard ratios (HR) for infections in patients with NAFLD compared to comparators. Cumulative incidences were calculated while accounting for competing risks (non-infection death and liver transplantation).

Results: Severe infections leading to death or hospitalization occurred in 1990 (13.4%) patients with NAFLD and 9899 (7.2%) comparators during a median of 4.5 and 6.1 years of follow-up, respectively. The rate of severe infections per 1000 person-years was higher in patients with NAFLD (21.0) than comparators (9.1) independently of components related to the metabolic syndrome (adjusted HR 1.9, 95% CI = 1.8-2.0). Infection-related mortality was also higher in NAFLD compared to comparators (adjusted HR 1.8, 95% CI = 1.6-2.2). The 10-year cumulative incidence of severe infections was 16.6% (95% CI = 15.8-17.4) in NAFLD and 8.0% (95% CI = 7.8-8.2) in comparators.

Conclusion: NAFLD was associated with severe infections and infection-related mortality, independently of components associated with the metabolic syndrome. Increased clinical vigilance of severe infections in NAFLD may diminish the risk of premature death.