Antibiotic use and development of nonalcoholic fatty liver disease: A population-based case-control study.

BACKGROUND AND AIMS: Antibiotics affect the gut microbiome. Preclinical studies suggest a role of gut dysbiosis in the development of nonalcoholic fatty liver disease (NAFLD), but data from large cohorts with liver histology are lacking. METHODS: In this nationwide case-control study, Swedish adults with histologically confirmed early-stage NAFLD (total n = 2584; simple steatosis n = 1435; steatohepatitis (NASH) n = 383; non-cirrhotic fibrosis n = 766) diagnosed January 2007-April 2017 were included and matched to ≤5 population controls (n = 12 646) for age, sex, calendar year and county of residence. Data for cumulative antibiotic dispensations and defined daily doses were accrued until 1 year before the matching date. Using conditional logistic regression, multivariable-adjusted odds ratios (aORs) were calculated. In a secondary analysis, NAFLD patients were compared with their full siblings (n = 2837). RESULTS: Previous antibiotic use was seen in 1748 (68%) NAFLD patients versus 7001 (55%) controls, corresponding to 1.35-fold increased odds of NAFLD (95% CI = 1.21-1.51) in a dose-dependent manner (pfor trend < .001). Estimates were comparable for all histologic stages (p > .05). The highest risk of NAFLD was observed after treatment with fluoroquinolones (aOR 1.38; 95% CI = 1.17-1.59). Associations remained robust when patients were compared with their full siblings (aOR 1.29; 95% CI = 1.08-1.55). Antibiotic treatment was only linked to NAFLD in patients without metabolic syndrome (aOR 1.63; 95% CI = 1.35-1.91) but not in those with metabolic syndrome (aOR 1.09; 95% CI = 0.88-1.30). CONCLUSIONS: Antibiotic use may be a risk factor for incident NAFLD, especially in individuals without the metabolic syndrome. The risk was highest for fluoroquinolones and remained robust in sibling comparisons with whom individuals share genetic and early environmental susceptibilities.