Liver and Bile

Clin Gastroenterol Hepatol. 2023;21(13):3346–55.e19

Ebrahimi F, Simon TG, Hagström H, Söderling J, Wester A, Roelstraete B, Ludvigsson JF

Risk of severe infection in patients with biopsy-proven non-alcoholic fatty liver disease – A population-based cohort study

Background and aims: It has been suggested that patients with non-alcoholic fatty liver disease (NAFLD) might be at increased risk of severe infections, but large-scale data from cohorts with biopsy-proven NAFLD are lacking.
Methods: Population-based cohort study including all Swedish adults with histologically confirmed NAFLD (n = 12,133) from 1969 to 2017. NAFLD was defined as simple steatosis (n = 8232), non-fibrotic steatohepatitis (n = 1378), non-cirrhotic fibrosis (n = 1845), and cirrhosis (n = 678). Patients were matched to ≤ 5 population comparators (n = 57,516) by age, sex, calendar year, and county. Swedish national registers were used to ascertain incident severe infections requiring hospital admission. Multivariable adjusted Cox regression was used to estimate hazard ratios in NAFLD and histopathological subgroups.
Results: Over a median of 14.1 years, 4517 patients (37.2%) with NAFLD versus 15,075 comparators (26.2%) were hospitalized for severe infections. Patients with NAFLD had higher incidence of severe infections than comparators (32.3 vs. 17.0/1000 person-years; adjusted hazard ratio [aHR] = 1.71; 95% confidence interval [CI]: 1.63–1.79). The most frequent infections were respiratory (13.8/1000 person-years) and urinary tract infections (11.4/1000 person-years). The absolute risk difference at 20 years after NAFLD diagnosis was 17.3%, equal to 1 extra severe infection in every 6 patients with NAFLD. Risk of infection increased with worsening histological severity of NAFLD (simple steatosis [aHR = 1.64], non-fibrotic steatohepatitis [aHR = 1.84], non-cirrhotic fibrosis [aHR = 1.77], and cirrhosis [aHR = 2.32]. Also compared with their full siblings, patients with NAFLD were at increased risk of severe infections (aHR = 1.54; 95% CI: 1.40–1.70).

Conclusions: Patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD) were at significantly higher risk of incident severe infection requiring hospitalization both compared with the general population and compared with siblings. Excess risk was evident across all stages of NAFLD and increased with worsening disease severity.

Dr. F. Ebrahimi, Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden, E-Mail:

DOI: 10.1016/j.cgh.2023.05.013

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