LAUSR

1 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 Dear Editors: We read with interest the article by Tsai et al 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. This dysbiosis could lead to excess releasing of ammonia and endotoxins in the gut lumen and blood, causing hyperammonemia and then HE. We fully support the authors’ idea that drugs like PPIs can induce encephalopathy. The suggested hypothesis in their article can be conceivable, but mostly in cases in which blood ammonia levels are high, because of its enhanced production by the disturbed gut flora. We studied prospectively 202 cirrhotic patients admitted in our hepatologic intensive care unit (58 ± 11 years-old; 71% men; Model for End-stage Liver Disease of 21 ± 8; 39% admitted for gastrointestinal bleeding) to determine various causes of encephalopathy. Patient’s medical history was recorded, with special attention for drug intake, including self-medication. Ammonemia was measured at admission for each patient. Overall, 122 patients (60%) displayed encephalopathy. Patients with encephalopathy received significantlymore frequently PPIs as compared with those who had no encephalopathy (49% vs 33%; P 1⁄4 .0190). Interestingly, when considering ammonia levels, this was only true in the group of patients displaying low ammonia levels (<75 mmol/L), whereas intake of PPIs was not associated with the presence of encephalopathy in the group of patients displaying high ammonia levels. PPIs, as well as many other drugs often prescribed to cirrhotic patients like antibiotics, are agonist of efflux pumps like P-glycoprotein (P-gp, ABCB1) expressed on the blood– brain barrier (BBB). This protein, belonging to the