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Background & Aims Hepatic encephalopathy (HE) is a serious complication of cirrhosis and is associated with gut dysbiosis. Proton pump inhibitors (PPIs), frequently prescribed to patients with cirrhosis, can contribute to small-bowel bacterial overgrowth. We investigated whether PPI predisposes patients with cirrhosis to HE using a large database of patients. Methods We performed a case–control study nested within a sample of Taiwan National Health Insurance beneficiaries (n = 1,000,000), followed up longitudinally from 1998 through 2011. Patients with cirrhosis and an occurrence of HE (n = 1166) were selected as the case cohort and matched to patients without HE (1:1, controls) for sex, enrollment time, end point time, follow-up period, and advanced cirrhosis. Information on prescribed drugs, drug dosage, supply days, and numbers of dispensed pills was extracted from the Taiwan National Health Insurance database. PPI use was defined as more than 30 cumulative defined daily doses (cDDDs); PPI nonuse was defined as 30 cDDDs or fewer. We performed logistic regression analyses to estimate the association between PPI use and the occurrence of HE. Results Among patients with cirrhosis and an occurrence of HE, 38% (n = 445) had a history of PPI use before HE occurrence. We observed a relationship between dose of PPI taken and HE risk. The confounder-adjusted odd ratios were 1.41 (95% confidence interval [CI], 1.09–1.84), 1.51 (95% CI, 1.11–2.06), and 3.01 (95% CI, 1.78–5.10) for patients with 30–120 cDDDs, 120–365 cDDDs, and more than 365 cDDDs, respectively, compared with PPI nonusers. All categories of PPIs, except rabeprazole, were associated with an increased risk of HE. Conclusions Based on an analysis of data from Taiwan National Health Insurance beneficiaries, we found that use of PPIs in patients with cirrhosis increases the risk for HE; risk increases with dose. It therefore is important for health care providers to carefully consider prolonged PPI use by patients with cirrhosis.

62 Question: A 60-year-old woman presented to our emergency room with epigastric fullness and passage of tarry stool for 1 week. She also had progressive shortness of breath, dizziness, and generalized weakness. On physical examination, slight tachycardia (heart rate, 104 bpm) with anemic conjunctiva was noted. Blood tests showed low hemoglobin (6.9 g/dL). Esophagogastroduodenoscopy revealed a polypoid tumor with superficial ulcerations and hematin coatings, suggesting recent bleeding, near superior duodenal angle of duodenum (Figure A). A barium study showed a filling defect over mesenteric side of second portion of duodenum, resulting in luminal narrowing (Figure B, black arrow). Biopsy at the overlying mucosa showed inflammatory changes without neoplastic cells. Abdominal computed tomography disclosed an enhancing soft tissue mass in the second portion of the duodenum (Figure C, D, white arrow). Tumor markers (carcinoembryonic antigen and carbohydrate antigen 19-9) were within normal limits. The patient underwent pancreaticoduodenotomy with limited antrectomy to remove the tumor. What is your diagnosis of this duodenal tumor? Look on page 261 for the answer and see the GASTROENTEROLOGY web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.