Association between anti-acid therapies and advanced fibrosis in type 2 diabetics with biopsy-proven non-alcoholic fatty liver disease

Backgrounds and Aims: Data on associations of antacid therapies with advanced fibrosis (AF) in patients with non-alcoholic fatty liver disease (NAFLD) are limited. We aimed to assess the association of histamine-2 receptor antagonists (H₂RAs) and proton pump inhibitors (PPIs) with AF in NAFLD patients with underlying type 2 diabetes (T2D). Methods: We retrospectively reviewed patient’s charts with T2D who had a liver biopsy for suspected NAFLD. Fibrosis stages were determined as F0–F4, AF being F3–4. Laboratory data and use of various medications within 24 months of liver biopsies were used for the analysis. Univariable and multivariable logistic regression analyses were performed to assess any association. Results: Our cohort consisted of 1008 T2D patients with biopsy-proven NAFLD. Sixty-six percent were female, 86.2% were Caucasian, and median HbA₁C was 6.4%. AF was present in 32% of the patients. Thirty-four percent were on H₂RAs and 60.6% were on PPI therapy (p < 0.001) for a median duration of 3.6 [0.10, 3.8] (p = 0.20) and 45.6 [0.80, 15.4] (p = 0.17) months, respectively. On multivariable logistic regression analysis being on H₂RAs was associated with a 68% lower risk of AF (odds ratio [OR] [95%CI]: 0.32 [0.24, 0.44]) (p < 0.001), but use of PPIs showed a trend towards higher risk of AF (OR [95%CI]: 1.4 [1.00, 1.8]) (p = 0.053). Conclusion: Our study suggests that H₂RAs are associated with lower risk of AF in NAFLD patients with underlying diabetes and should be considered as the first-line antacid therapy in these patients. Risk stratification should be done if PPIs are indicated in high-risk diabetics with NAFLD.