Risk of Severe Infection in Patients With Biopsy-proven Nonalcoholic Fatty Liver Disease - A Population-based Cohort Study

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

doi:10.1016/j.cgh.2023.05.013

Risk of Severe Infection in Patients With Biopsy-proven Nonalcoholic Fatty Liver Disease - A Population-based Cohort Study

Clin Gastroenterol Hepatol. 2023 Dec;21(13):3346-3355.e19. doi: 10.1016/j.cgh.2023.05.013. Epub 2023 May 26.

Authors

Fahim Ebrahimi¹, Tracey G Simon², Hannes Hagström³, Jonas Söderling⁴, Axel Wester⁵, Bjorn Roelstraete⁶, Jonas F Ludvigsson⁷

Affiliations

¹ 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.
² Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Division of Gastroenterology and Hepatology, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital, Boston, Massachusetts.
³ Division of Hepatology, Department of Upper GI, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
⁴ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Clinical Epidemiology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
⁵ Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
⁶ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁷ 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.

PMID: 37245712
DOI: 10.1016/j.cgh.2023.05.013

Abstract

Background & aims: It has been suggested that patients with nonalcoholic 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), nonfibrotic steatohepatitis (n = 1378), noncirrhotic 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 (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. 17.0/1000 person-years; adjusted hazard ratio [aHR], 1.71; 95% confidence interval, 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 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], nonfibrotic steatohepatitis [aHR, 1.84], noncirrhotic 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% confidence interval, 1.40-1.70).

Conclusions: Patients with biopsy-proven 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.

Keywords: Hospitalization; Immune System; Infection; Metabolic Syndrome; Nonalcoholic Fatty Liver Disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Biopsy
Cohort Studies
Humans
Incidence
Liver / pathology
Liver Cirrhosis / epidemiology
Liver Cirrhosis / pathology
Non-alcoholic Fatty Liver Disease* / complications
Non-alcoholic Fatty Liver Disease* / epidemiology
Non-alcoholic Fatty Liver Disease* / pathology