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J Clin Gastroenterol. 2016 Aug;50(7):596-601. doi: 10.1097/MCG.0000000000000503.

Histamine H2-Receptor Antagonist Use Is Associated With Lower Prevalence of Nonalcoholic Fatty Liver Disease: A Population-based Study From the National Health and Nutrition Examination Survey, 2001-2006.

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*Department of Medicine, Division of Gastroenterology and Hepatology, University of Iowa, Iowa City, IA †Department of Medicine, Division of Gastroenterology and Hepatology, Indiana University ‡Roudebush Veterans Administration Medical Center, Indianapolis, IN.



Recent basic mechanistic studies found that proton-pump inhibitors (PPIs) or histamine antagonists inhibited multiple pathways involved in nonalcoholic fatty liver disease (NAFLD) development. The aim of this study was to investigate an association between PPIs or H1/H2-receptor antagonist (H1RA/H2RA) use and NAFLD prevalence in the general US population.


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 to 74 years who had alanine aminotransferase data; of those, 2058 were identified as having NAFLD and 8340 as controls. PPI or H1RA/H2RA 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.


In the multivariate unconditional logistic regression analysis, H2RA 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 PPI or H1RA use and prevalent NAFLD.


These findings, from the first human study to investigate an association of PPI or H1RA/H2RA use with NAFLD, suggest that H2RA use may be associated with a lower prevalence of NAFLD, primarily among men with insulin resistance.

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