{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T21:38:07Z","timestamp":1776893887370,"version":"3.51.2"},"reference-count":44,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T00:00:00Z","timestamp":1751068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: Proton pump inhibitors (PPIs) are frequently used after endoscopic variceal ligation (EVL) to reduce post-procedural bleeding, though studies have shown mixed results regarding their efficacy. While some suggest benefits, others report no significant advantage and highlight potential risks, including infection, kidney injury, and hepatic complications in cirrhotic patients. This study utilizes the TriNetX global health research network to evaluate the outcomes of PPI use following elective EVL for primary prophylaxis. Methods: This retrospective cohort study was conducted using the TriNetX database to evaluate adult patients with cirrhosis and esophageal varices who underwent EVL for primary prophylaxis. Patients who received at least two weeks of PPI therapy following EVL were compared to those who did not receive PPI within one month post-procedure. Outcomes assessed included esophageal bleeding, adverse events such as acute kidney injury (AKI), pneumonia, spontaneous bacterial peritonitis (SBP), Clostridioides difficile infection, hepatic encephalopathy, and all-cause mortality at 4 weeks and 8 weeks. Results: Of 6196 patients with cirrhosis and esophageal varices who underwent EVL, 12% (n = 764) received adjuvant PPI post-procedure, while 88% (n = 5432) did not receive PPI. After 1:1 propensity score matching, two well-balanced cohorts of 618 patients each were analyzed. PPI use was not associated with a reduction in esophageal bleeding at either 4 weeks (1.8% vs. 1.7%, p = 0.89) or 8 weeks (2.3% vs. 1.9%, p = 0.60). However, the composite adverse event rate\u2014including SBP, hepatic encephalopathy, pneumonia, C. difficile, and acute kidney injury (AKI)\u2014was significantly higher in the PPI group at both 4 weeks (7.9% vs. 3.0%, p &lt; 0.01) and 8 weeks (13.2% vs. 3.0%, p &lt; 0.01). Subgroup analysis showed no significant differences in pneumonia, SBP, or C. difficile infection at either time point. Hepatic encephalopathy was significantly more frequent in the PPI group at 8 weeks (4.9% vs. 2.0%, p = 0.01), and AKI occurred more often at both 4 weeks (5.7% vs. 2.0%, p &lt; 0.01) and 8 weeks (9.6% vs. 2.1%, p &lt; 0.01). Mortality was similar at 4 weeks but significantly higher in the PPI group at 8 weeks (4.3% vs. 1.7%, p &lt; 0.01). Conclusions: PPI use after prophylactic EVL did not reduce bleeding risk and was linked to higher rates of adverse events. These findings suggest routine use may not be beneficial and should be reconsidered in cirrhotic patients who undergo EVL for primary prophylaxis.<\/jats:p>","DOI":"10.3390\/diagnostics15131653","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T05:00:37Z","timestamp":1751259637000},"page":"1653","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Proton Pump Inhibitor Use Following Esophageal Variceal Ligation and Its Impact on Clinical Outcomes: Real-World Data from the TriNetX Global Collaborative Network"],"prefix":"10.3390","volume":"15","author":[{"given":"Nisar","family":"Amin","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Charleston Area Medical Center, Charleston, WV 25304, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harleen","family":"Chela","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Charleston Area Medical Center, Charleston, WV 25304, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad Faisal","family":"Mubarak","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, College of Medicine, King Saudi University, Riyadh 11451, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6518-3971","authenticated-orcid":false,"given":"Mark","family":"Ayoub","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Charleston Area Medical Center, Charleston, WV 25304, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0622-1704","authenticated-orcid":false,"given":"Ebubekir","family":"Daglilar","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Charleston Area Medical Center, Charleston, WV 25304, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1002\/hep.21907","article-title":"Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis","volume":"46","author":"Sanyal","year":"2007","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/S1089-3261(05)70186-0","article-title":"Natural history of portal hypertension in patients with cirrhosis","volume":"5","author":"Primignani","year":"2001","journal-title":"Clin. Liver Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1053\/gast.2001.22580","article-title":"Current management of the complications of cirrhosis and portal hypertension: Variceal hemorrhage, ascites, and spontaneous bacterial peritonitis","volume":"120","year":"2001","journal-title":"Gastroenterology"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"North Italian Endoscopic Club for the Study and Treatment of Esophageal Varices (1988). Prediction of the first variceal hemorrhage in patients with cirrhosis of the liver and esophageal varices. A prospective multicenter study. N. Engl. J. Med., 319, 983\u2013989.","DOI":"10.1056\/NEJM198810133191505"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1016\/j.cgh.2014.11.019","article-title":"Risk of Bacterial Infection in Patients with Cirrhosis and Acute Variceal Hemorrhage, Based on Child-Pugh Class, and Effects of Antibiotics","volume":"13","author":"Tandon","year":"2015","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1016\/S0140-6736(03)12778-X","article-title":"Prevention of variceal rebleeding","volume":"361","author":"Bosch","year":"2003","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/j.jhep.2021.12.022","article-title":"Baveno VII\u2014Renewing consensus in portal hypertension","volume":"76","author":"Bosch","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1097\/HEP.0000000000000647","article-title":"AASLD Practice Guidance on risk stratification and management of portal hypertension and varices in cirrhosis","volume":"79","author":"Kaplan","year":"2024","journal-title":"Hepatology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1016\/S0140-6736(18)31875-0","article-title":"\u03b2 blockers to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension (PREDESCI): A randomised, double-blind, placebo-controlled, multicentre trial","volume":"393","author":"Villanueva","year":"2019","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1111\/apt.12634","article-title":"Systematic review with meta-analysis: The haemodynamic effects of carvedilol compared with propranolol for portal hypertension in cirrhosis","volume":"39","author":"Sinagra","year":"2014","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1002\/hep.28906","article-title":"Portal hypertensive bleeding in cirrhosis: Risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases","volume":"65","author":"Abraldes","year":"2017","journal-title":"Hepatology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1002\/hep.20284","article-title":"Ligation versus propranolol for the primary prophylaxis of variceal bleeding in cirrhosis","volume":"40","author":"Schepke","year":"2004","journal-title":"Hepatology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1038\/ncpgasthep0323","article-title":"Endoscopic band ligation in the treatment of portal hypertension","volume":"2","author":"Bosch","year":"2005","journal-title":"Nat. Clin. Pract. Gastroenterol. Hepatol."},{"key":"ref_14","first-page":"144","article-title":"Symptomatic esophageal stricture after endoscopic variceal ligation\u2014Success of endoscopic balloon dilation","volume":"63","author":"Chen","year":"2000","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"ref_15","first-page":"557","article-title":"Complete esophageal obstruction following endoscopic variceal ligation","volume":"7","author":"Nikoloff","year":"2011","journal-title":"Gastroenterol. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Amin, N., Ayoub, M., Tomanguillo, J., Chela, H., Tahan, V., and Daglilar, E. (2025). Outcomes of Outpatient Elective Esophageal Varices Band Ligation in Cirrhosis Patients with Significant Thrombocytopenia. Diseases, 13.","DOI":"10.3390\/diseases13020027"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1111\/j.1365-2036.2010.04331.x","article-title":"Predictive factors of bleeding related to post-banding ulcer following endoscopic variceal ligation in cirrhotic patients: A case-control study","volume":"32","author":"Vanbiervliet","year":"2010","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e2903","DOI":"10.1097\/MD.0000000000002903","article-title":"Proton Pump Inhibitor Therapy Is Associated with Reduction of Early Bleeding Risk After Prophylactic Endoscopic Variceal Band Ligation: A Retrospective Cohort Study","volume":"95","author":"Kang","year":"2016","journal-title":"Medicine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1007\/s00535-011-0472-0","article-title":"Long-term administration of PPI reduces treatment failures after esophageal variceal band ligation: A randomized, controlled trial","volume":"47","author":"Hidaka","year":"2012","journal-title":"J. Gastroenterol."},{"key":"ref_20","first-page":"e33932","article-title":"Effectiveness of Proton Pump Inhibitor Therapy in the Prevention of Bleeding After Prophylactic Endoscopic Variceal Band Ligation","volume":"15","author":"Khawaja","year":"2023","journal-title":"Cureus"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"17127","DOI":"10.3748\/wjg.v20.i45.17127","article-title":"Proton pump inhibitor administration delays rebleeding after endoscopic gastric variceal obturation","volume":"20","author":"Jang","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1002\/hep.20593","article-title":"Pantoprazole reduces the size of postbanding ulcers after variceal band ligation: A randomized, controlled trial","volume":"41","author":"Shaheen","year":"2005","journal-title":"Hepatology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2980","DOI":"10.3748\/wjg.14.2980","article-title":"Proton pump inhibitors in cirrhosis: Tradition or evidence based practice?","volume":"14","author":"Lodato","year":"2008","journal-title":"World J. Gastroenterol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5869","DOI":"10.3748\/wjg.v16.i46.5869","article-title":"PPIs are not associated with a lower incidence of portal-hypertension-related bleeding in cirrhosis","volume":"16","year":"2010","journal-title":"World J. Gastroenterol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e7157","DOI":"10.1097\/MD.0000000000007157","article-title":"Endoscopic variceal ligation-induced ulcer bleeding: What are the risk factors and treatment strategies?","volume":"96","author":"Cho","year":"2017","journal-title":"Medicine"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1002\/hep.30304","article-title":"Proton Pump Inhibitors Are Associated with Minimal and Overt Hepatic Encephalopathy and Increased Mortality in Patients with Cirrhosis","volume":"70","author":"Nardelli","year":"2019","journal-title":"Hepatology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1053\/j.gastro.2016.09.007","article-title":"Proton Pump Inhibitors Increase Risk for Hepatic Encephalopathy in Patients with Cirrhosis in A Population Study","volume":"152","author":"Tsai","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1053\/j.gastro.2017.01.031","article-title":"The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice from the American Gastroenterological Association","volume":"152","author":"Freedberg","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.14309\/ajg.0000000000000798","article-title":"Increased Risk of COVID-19 Among Users of Proton Pump Inhibitors","volume":"115","author":"Almario","year":"2020","journal-title":"Am. J. Gastroenterol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1001\/jamainternmed.2015.42","article-title":"Continuous Proton Pump Inhibitor Therapy and the Associated Risk of Recurrent Clostridium difficile Infection","volume":"175","author":"McDonald","year":"2015","journal-title":"JAMA Intern. Med."},{"key":"ref_31","unstructured":"(2025, April 27). TrinetX. Available online: https:\/\/trinetx.com\/."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1097\/IMNA-D-22-00027","article-title":"Research Progress on the Potential Mechanisms of Acute Kidney Injury and Chronic Kidney Disease Induced by Proton Pump Inhibitors","volume":"10","author":"Song","year":"2023","journal-title":"Integr. Med. Nephrol. Androl."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1038\/ki.2014.74","article-title":"A nationwide nested case-control study indicates an increased risk of acute interstitial nephritis with proton pump inhibitor use","volume":"86","author":"Blank","year":"2014","journal-title":"Kidney Int."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1111\/j.1365-2036.2007.03407.x","article-title":"Systematic review: Proton pump inhibitor-associated acute interstitial nephritis","volume":"26","author":"Sierra","year":"2007","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1002\/hep.28737","article-title":"Proton pump inhibitors as a risk factor for hepatic encephalopathy and spontaneous bacterial peritonitis in patients with cirrhosis with ascites","volume":"64","author":"Dam","year":"2016","journal-title":"Hepatology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2683","DOI":"10.3748\/wjg.v25.i21.2683","article-title":"Association of proton pump inhibitors with risk of hepatic encephalopathy in advanced liver disease: A meta-analysis","volume":"25","author":"Tantai","year":"2019","journal-title":"World J. Gastroenterol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1053\/j.gastro.2022.03.052","article-title":"The Association Between Proton Pump Inhibitor Exposure and Key Liver-Related Outcomes in Patients with Cirrhosis: A Veterans Affairs Cohort Study","volume":"163","author":"Mahmud","year":"2022","journal-title":"Gastroenterology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1007\/s00535-023-02007-5","article-title":"Proton pump inhibitor use and risk of pneumonia: A self-controlled case series study","volume":"58","author":"Panula","year":"2023","journal-title":"J. Gastroenterol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6500","DOI":"10.3748\/wjg.v23.i35.6500","article-title":"Proton pump inhibitors therapy and risk of Clostridium difficile infection: Systematic review and meta-analysis","volume":"23","author":"Trifan","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2883","DOI":"10.1128\/AAC.01443-06","article-title":"Vegetative Clostridium difficile survives in room air on moist surfaces and in gastric contents with reduced acidity: A potential mechanism to explain the association between proton pump inhibitors and C. difficile-associated diarrhea?","volume":"51","author":"Jump","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1136\/gutjnl-2015-310376","article-title":"Proton pump inhibitors affect the gut microbiome","volume":"65","author":"Imhann","year":"2016","journal-title":"Gut"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1111\/jgh.12426","article-title":"Mortality associated with proton pump inhibitors in cirrhotic patients with spontaneous bacterial peritonitis","volume":"29","author":"Kwon","year":"2014","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"doad060","DOI":"10.1093\/dote\/doad060","article-title":"Is proton-pump inhibitor effective in preventing postoperative bleeding after esophageal endoscopic submucosal dissection?","volume":"37","author":"Tanaka","year":"2024","journal-title":"Dis. Esophagus"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1756284820974908","DOI":"10.1177\/1756284820974908","article-title":"Is a proton-pump inhibitor necessary after endoscopic submucosal dissection for superficial esophageal neoplasms? A propensity score analysis","volume":"13","author":"Kanaoka","year":"2020","journal-title":"Therap. Adv. Gastroenterol."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/13\/1653\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:00:52Z","timestamp":1760032852000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/13\/1653"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,28]]},"references-count":44,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["diagnostics15131653"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics15131653","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,28]]}}}