We read with interest the article by Tsai et al1 in a recent issue of Gastroenterology, which highlights the influence of proton pump inhibitors (PPIs) use on encephalopathy occurrence in cirrhotic patients. This case control study performed in a large series of cirrhotic patients demonstrated a relationship between PPIs intake and the onset of a first hepatic encephalopathy (HE) episode, outlining a dose-dependent risk (odds ratios from 1.41 to 3.01). The authors explained the increased risk of HE by an alteration of gut microbiota under PPIs treatment, which equilibrium also seems to be disrupted in cirrhotic patients, especially during HE.