{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:12:22Z","timestamp":1792541542507,"version":"4.5.0"},"reference-count":30,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background\/Objectives: Nonselective beta-blockers (NSBBs) are foundational for variceal bleeding prophylaxis in cirrhosis. After transjugular intrahepatic portosystemic shunt (TIPS) placement, portal pressure is mechanically decompressed, and practice guidance generally supports discontinuing NSBBs when shunt function is adequate and no other indication exists; however, real-world adoption and outcomes associated with post-TIPS NSBB strategies remain incompletely characterized in large, multicenter populations. Methods: We performed a real-world, target-trial emulation in the TriNetX U.S. Collaborative Network using a prespecified 90-day landmark. Adults (\u226518 years) with cirrhosis undergoing first TIPS who had NSBB prescribed in the prior year and who survived to post-TIPS day 90 were included. Strategy was classified during days 0\u201390 (continuation: \u22651 NSBB prescription; discontinuation: none). Propensity score matching (1:1) balanced demographics, comorbidities, portal hypertension complications, and laboratory values (including the components of the Freiburg Index of Post-TIPS Survival [FIPS], Model for End-stage Liver Disease\u2013Sodium [MELD-Na], and Child\u2013Pugh scores). Follow-up began at day 90 and continued through day 365. Primary outcomes were overall survival and transplant-free survival; secondary outcomes were hepatic encephalopathy (HE), esophageal variceal bleeding (EVB), and ICU admission. Results: Among 5111 patients (continuation: n = 2558; discontinuation: n = 2553), 2180 matched pairs were analyzed. One-year survival was similar (89.3% vs. 89.6%; HR: 1.03; 95% CI: 0.84\u20131.27), as was transplant-free survival (78.8% vs. 77.9%; HR: 0.95; 95% CI: 0.82\u20131.10). The cause-specific hazard of HE was higher with continuation (HR; 1.29; 95% CI: 1.14\u20131.46), while those of EVB (HR: 1.08; 95% CI: 0.90\u20131.29) and ICU admission (HR: 1.02; 95% CI: 0.86\u20131.22) were similar. Results were consistent in both strict discontinuation and adherence-based sensitivity analyses. Conclusions: In stabilized post-TIPS patients with prior NSBB use, continuation was not associated with improved 1-year survival or transplant-free survival and was associated with a higher cause-specific hazard of HE.<\/jats:p>","DOI":"10.3390\/jcm15155881","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T07:55:41Z","timestamp":1785225341000},"page":"5881","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Continuation Versus Discontinuation of Nonselective Beta-Blockers After Transjugular Intrahepatic Portosystemic Shunt Placement: A Real-World, Target-Trial Emulation Analysis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3073-8538","authenticated-orcid":false,"given":"Ali Emre","family":"Bardak","sequence":"first","affiliation":[{"name":"Department of Medicine, Boston Medical Center-Brighton, Boston, MA 02135, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayse Ipek","family":"Bardak","sequence":"additional","affiliation":[{"name":"Center for Computational Molecular Biology, Brown University, Providence, RI 02906, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gizem","family":"Teker","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hind El","family":"Naamani","sequence":"additional","affiliation":[{"name":"Department of Medicine, Boston Medical Center-Brighton, Boston, MA 02135, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elif Gokcek","family":"Uskudar","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4363-7197","authenticated-orcid":false,"given":"Volkan","family":"Senkal","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Istanbul University, Istanbul 34452, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bilger","family":"Cavus","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Istanbul University, Istanbul 34452, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazli Begum","family":"Ozturk","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2221-9148","authenticated-orcid":false,"given":"Ahmet","family":"Gurakar","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1053\/j.gastro.2015.05.011","article-title":"Prevention of rebleeding from esophageal varices in patients with cirrhosis receiving small-diameter stents versus hemodynamically controlled medical therapy","volume":"149","author":"Sauerbruch","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1111\/apt.18204","article-title":"No value of non-selective beta-blockers after TIPS-insertion","volume":"60","author":"Tiede","year":"2024","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_4","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_5","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1097\/HEP.0000000000000530","article-title":"AASLD Practice Guidance on the use of TIPS, variceal embolization, and retrograde transvenous obliteration in the management of variceal hemorrhage","volume":"79","author":"Lee","year":"2024","journal-title":"Hepatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.jhep.2025.01.029","article-title":"EASL Clinical Practice Guidelines on TIPS","volume":"83","author":"Bureau","year":"2025","journal-title":"J. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1002\/hep.30934","article-title":"A prospective study identifying predictive factors of cardiac decompensation after transjugular intrahepatic portosystemic shunt: The Toulouse algorithm","volume":"70","author":"Billey","year":"2019","journal-title":"Hepatology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1056\/NEJMra1504367","article-title":"Treatment of patients with cirrhosis","volume":"375","author":"Ge","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1016\/j.jhep.2021.01.023","article-title":"Refining prediction of survival after TIPS with the novel Freiburg index of post-TIPS survival","volume":"74","author":"Bettinger","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4007","DOI":"10.2147\/IJGM.S359918","article-title":"Prediction of patient hepatic encephalopathy risk with Freiburg index of post-TIPS survival score following transjugular intrahepatic portosystemic shunts: A retrospective study","volume":"15","author":"Cai","year":"2022","journal-title":"Int. J. Gen. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1080\/00273171.2011.568786","article-title":"An introduction to propensity score methods for reducing the effects of confounding in observational studies","volume":"46","author":"Austin","year":"2011","journal-title":"Multivar. Behav. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1093\/eurheartj\/ehy770","article-title":"Limitations of hazard ratios in clinical trials","volume":"40","author":"Stensrud","year":"2019","journal-title":"Eur. Heart J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1002\/sim.8471","article-title":"A causal framework for classical statistical estimands in failure-time settings with competing events","volume":"39","author":"Young","year":"2020","journal-title":"Stat. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.jclinepi.2016.07.013","article-title":"Competing risk bias was common in a prominent medical journal","volume":"80","author":"Schumacher","year":"2016","journal-title":"J. Clin. Epidemiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1093\/aje\/kwm324","article-title":"Immortal time bias in pharmacoepidemiology","volume":"167","author":"Suissa","year":"2008","journal-title":"Am. J. Epidemiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1016\/j.clinthera.2020.04.014","article-title":"Comparison of therapies for secondary prophylaxis of esophageal variceal bleeding in cirrhosis: A network meta-analysis of randomized controlled trials","volume":"42","author":"Miao","year":"2020","journal-title":"Clin. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1056\/NEJMra1600561","article-title":"Hepatic encephalopathy","volume":"375","author":"Wijdicks","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1111\/apt.16825","article-title":"Review article: Post-TIPSS hepatic encephalopathy\u2014Current knowledge and future perspectives","volume":"55","author":"Gairing","year":"2022","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Friis, K.H., Thomsen, K.L., Laleman, W., Montagnese, S., Vilstrup, H., and Lauridsen, M.M. (2023). Post-transjugular intrahepatic portosystemic shunt (TIPS) hepatic encephalopathy\u2014A review of the past decade\u2019s literature focusing on incidence, risk factors, and prophylaxis. J. Clin. Med., 13.","DOI":"10.3390\/jcm13010014"},{"key":"ref_20","first-page":"103512","article-title":"Management of hepatic encephalopathy following transjugular intrahepatic portosystemic shunts: Current strategies and future directions","volume":"31","author":"Li","year":"2025","journal-title":"World J. Gastroenterol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1001\/jama.2023.5997","article-title":"Diagnosis and management of cirrhosis and its complications: A review","volume":"329","author":"Tapper","year":"2023","journal-title":"JAMA"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Nabilou, P., Danielsen, K.V., Kimer, N., Hove, J.D., Bendtsen, F., and M\u00f8ller, S. (2022). Blunted cardiovascular effects of beta-blockers in patients with cirrhosis: Relation to severity?. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0270603"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/j.jhep.2016.11.001","article-title":"Beta adrenergic blockade and decompensated cirrhosis","volume":"66","author":"Reiberger","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1111\/liv.15166","article-title":"Non-selective beta-blockers in patients with ascites: The complex interplay among the liver, kidney and heart","volume":"42","author":"Albillos","year":"2022","journal-title":"Liver Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ejim.2020.08.022","article-title":"Impact of non-selective \u03b2-blockers on hepatic encephalopathy in patients with liver cirrhosis","volume":"82","author":"Labenz","year":"2020","journal-title":"Eur. J. Intern. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/j.jhep.2022.12.005","article-title":"Beta-blockers in the era of precision medicine in patients with cirrhosis","volume":"78","author":"Albillos","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.jhep.2023.11.033","article-title":"Episodic overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt does not increase mortality in patients with cirrhosis","volume":"80","author":"Nardelli","year":"2024","journal-title":"J. Hepatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1111\/apt.18509","article-title":"Post-TIPS overt hepatic encephalopathy increases long-term but not short-term mortality in cirrhotic patients with variceal bleeding: A large-scale, multicenter real-world study","volume":"61","author":"Xiang","year":"2025","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_29","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_30","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1007\/s10620-025-09453-6","article-title":"Comparative risk of recurrent esophageal variceal hemorrhage and other decompensation events with carvedilol versus propranolol in patients with cirrhosis: A retrospective study","volume":"71","author":"Ismail","year":"2025","journal-title":"Dig. Dis. Sci."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/15\/5881\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T08:23:14Z","timestamp":1785226994000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/15\/5881"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,28]]},"references-count":30,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["jcm15155881"],"URL":"https:\/\/doi.org\/10.3390\/jcm15155881","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,28]]}}}