Background & Aim Recent basic mechanistic studies found that proton pump inhibitors (PPIs) or histamine antagonists inhibited multiple pathways involved in non-alcoholic fatty liver disease (NAFLD) development. The aim of this study was to investigate an association between PPIs or H1/H2-receptor antagonists (H1RAs/H2RAs) use and NAFLD prevalence in the general US population.

Methods We conducted a cross-sectional analysis of data from the National Health and Nutrition Examination Survey, 2001 – 2006. We included 10,398 adults aged 20 – 74 years who had alanine aminotransferase (ALT) data; of those, 2,058 were identified as having NAFLD and 8,340 as controls. PPIs or H1RAs/H2RAs use was defined as use of prescription medications in the preceding month. The length of use was categorized as ≤ 60 days and > 60 days. NAFLD was defined as elevated serum aminotransferases without any indication of other causes of chronic liver disease.

Results In the multivariate unconditional logistic regression analysis, H2RAs use was inversely associated with prevalent NAFLD (odds ratio [OR] = 0.43, 95% confidence interval [CI] 0.18 – 0.99), a finding that was primarily limited to men (OR = 0.18, 95% CI 0.04 – 0.79) and those with insulin resistance (OR = 0.22, 95% CI 0.05 – 0.95). However, no significant associations were found between PPIs or H1RAs use and prevalent NAFLD.

Conclusion These findings, from the first human study to investigate an association of PPIs or H1RAs/H2RAs use with NAFLD, suggest that H2RAs use may be associated with a lower prevalence of NAFLD, primarily among men with insulin resistance.