Proton Pump Inhibitors Use is Associated with Increased Liver Steatosis: A Nationally Representative Study

Abstract

Abstract Purpose Despite the generally considered safety of proton pump inhibitors (PPIs), growing evidence and concerns have raised questions about their potential long-term complications. This study aimed to investigate the association between PPIs therapy and the prevalence of hepatic steatosis and liver fibrosis in the outpatient population of the United States. Methods The study included 7,395 individuals aged 20 years and older who underwent hepatic vibration-controlled transient elastography (VCTE) examinations. Data were obtained from the 2017 and March 2020 pre-pandemic National Health and Nutrition Examination Survey. Results Among the 7,395 adults included in this study (mean age, 50.59 years; 3,656 males), 9.8% had a prescription for PPIs. After multivariable adjustment, the use of PPIs was significantly associated with hepatic steatosis (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.02–1.53). Prolonged use of PPIs was found to increase the risk of developing hepatic steatosis over time (p for trend = 0.006). Sensitivity analyses using different definitions of hepatic steatosis, such as controlled attenuation parameter ≥ 285 dB/m (OR, 1.19; 95% CI, 1.01–1.40), nonalcoholic fatty liver disease (OR, 1.50; 95% CI, 1.16–1.93), and metabolic dysfunction associated steatotic liver disease (OR, 1.26; 95% CI, 1.05–1.52), consistently showed an association between PPIs prescription and hepatic steatosis. Conclusion The administration of PPIs therapy has been found to be linked with heightened hepatic steatosis in US adults, although no significant correlation was observed with liver stiffness, as determined by VCTE.