Risk of Severe Infection in Patients with Biopsy-Proven Non-Alcoholic Fatty Liver Disease – A Population-Based Cohort Study.

May 29, 2023

Experts: Fahim Ebrahimi,Tracey G Simon,Hannes Hagström,Jonas Söderling,Axel Wester,Bjorn Roelstraete,Jonas F Ludvigsson

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.
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=8,232), non-fibrotic steatohepatitis(n=1,378), non-cirrhotic fibrosis(n=1,845) 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 (HRs) in NAFLD and histopathological subgroups.
Over a median of 14.1 years, 4,517(37.2%) patients with NAFLD vs. 15,075 (26.2%) comparators were hospitalized for severe infections. Patients with NAFLD had higher incidence of severe infections than comparators (32.3 vs. 17.0/1,000 person-years; aHR=1.71;95%CI=1.63-1.79). The most frequent infections were respiratory (13.8/1,000 person-years) and urinary tract infections (11.4/1,000 person-years). The absolute risk difference at 20 years after NAFLD diagnosis was 17.3%, equal to one 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).
Patients with biopsy-proven NAFLD were at significantly higher risk of incident severe infection requiring hospitalization both compared to the general population and compared to siblings. Excess risk was evident across all stages of NAFLD and increased with worsening disease severity.

Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.

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ABOUT THE EXPERTS

Fahim Ebrahimi,Tracey G Simon,Hannes Hagström,Jonas Söderling,Axel Wester,Bjorn Roelstraete,Jonas F Ludvigsson

Fahim Ebrahimi

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Gastroenterology and Hepatology, University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland. Electronic address: fahim.ebrahimi@ki.se.

Tracey G Simon

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Division of Gastroenterology and Hepatology, Massachusetts General Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA; Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital, Boston, Massachusetts, USA. Electronic address: tgsimon@mgh.harvard.edu.

Hannes Hagström

Division of Hepatology, Department of Upper GI, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden. Electronic address: hannes.hagstrom@ki.se.

Jonas Söderling

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Clinical Epidemiology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden. Electronic address: jonas.soderling@ki.se.

Axel Wester

Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden. Electronic address: axel.wester@ki.se.

Bjorn Roelstraete

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Electronic address: bjorn.roelstraete@ki.se.

Jonas F Ludvigsson

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA. Electronic address: jonas.ludvigsson@ki.se.