{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:24:43Z","timestamp":1792290283639,"version":"4.4.0"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","license":[{"start":{"date-parts":[[2019,6,20]],"date-time":"2019-06-20T00:00:00Z","timestamp":1560988800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver Transpl"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:p>In patients with hepatocellular carcinoma (HCC) meeting the Milan criteria (MC), the benefit of locoregional therapies (LRTs) in the context of liver transplantation (LT) is still debated. Initial biases in the selection between treated and untreated patients have yielded conflicting reported results. The study aimed to identify, using a competing risk analysis, risk factors for HCC\u2010dependent LT failure, defined as pretransplant tumor\u2010related delisting or posttransplant recurrence. The study was registered at www.clinicaltrials.gov (identification number NCT03723304). In order to offset the initial limitations of the investigated population, an inverse probability of treatment weighting (IPTW) analysis was used: 1083 MC\u2010in patients (no LRT\u00a0=\u00a0182; LRT\u00a0=\u00a0901) were balanced using 8 variables: age, sex, Model for End\u2010Stage Liver Disease (MELD) value, hepatitis C virus status, hepatitis B virus status, largest lesion diameter, number of nodules, and alpha\u2010fetoprotein (AFP). All the covariates were available at the first referral. After the IPTW, a pseudo\u2010population of 2019 patients listed for LT was analyzed, comparing 2 homogeneous groups of untreated (n\u00a0=\u00a01077) and LRT\u2010treated (n\u00a0=\u00a0942) patients. Tumor progression after LRT was the most important independent risk factor for HCC\u2010dependent failure (subhazard ratio [SHR], 5.62; <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0&lt;\u00a00.001). Other independent risk factors were major tumor diameter, AFP, MELD, patient age, male sex, and period of wait\u2010list registration. One single LRT was protective compared with no treatment (SHR, 0.51; <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0&lt;\u00a00.001). The positive effect was still observed when 2\u20103 treatments were performed (SHR, 0.66; <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.02), but it was lost in the case of \u22654 LRTs (SHR, 0.80; <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.27). In conclusion, for MC\u2010in patients, up to 3 LRTs are beneficial for success in intention\u2010to\u2010treat LT patients, with a 49% to 34% reduction in failure risk compared with untreated patients. This benefit is lost if more LRTs are required. A poor response to LRT is associated with a higher risk for HCC\u2010dependent transplant failure.<\/jats:p>","DOI":"10.1002\/lt.25492","type":"journal-article","created":{"date-parts":[[2019,5,14]],"date-time":"2019-05-14T15:53:19Z","timestamp":1557849199000},"page":"1023-1033","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["The Intention\u2010to\u2010Treat Effect of Bridging Treatments in the Setting of Milan Criteria\u2013In Patients Waiting for Liver Transplantation"],"prefix":"10.1097","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1487-3235","authenticated-orcid":false,"given":"Quirino","family":"Lai","sequence":"first","affiliation":[{"name":"Starzl Abdominal Transplant Unit, P\u00f4le de Chirurgie Exp\u00e9rimentale et Transplantation, Institut de Recherche Exp\u00e9rimentale et Clinique,Universit\u00e9 Catholique de Louvain,Brussels,Belgium"},{"name":"Department of General Surgery and Organ Transplantation,Umberto I Hospital, Sapienza University,Rome,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Vitale","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology, and Gastroenterology,University of Padua,Padua,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuele","family":"Iesari","sequence":"additional","affiliation":[{"name":"Starzl Abdominal Transplant Unit, P\u00f4le de Chirurgie Exp\u00e9rimentale et Transplantation, Institut de Recherche Exp\u00e9rimentale et Clinique,Universit\u00e9 Catholique de Louvain,Brussels,Belgium"},{"name":"Department of Biotechnological and Applied Clinical Sciences,University of L\u2019Aquila,L\u2019Aquila,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armin","family":"Finkenstedt","sequence":"additional","affiliation":[{"name":"Department of Medicine I,Medical University Innsbruck,Innsbruck,Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Mennini","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Organ Transplantation,Umberto I Hospital, Sapienza University,Rome,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Onali","sequence":"additional","affiliation":[{"name":"University College London Institute for Liver and Digestive Health and Royal Free Sheila Sherlock Liver Centre,Royal Free Hospital and University College London,London,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Hoppe\u2010Lotichius","sequence":"additional","affiliation":[{"name":"Department of Transplantation and Hepatobiliary Surgery,University of Mainz,Mainz,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4636-3478","authenticated-orcid":false,"given":"Tommaso M.","family":"Manzia","sequence":"additional","affiliation":[{"name":"Department of Transplant Surgery, Polyclinic Tor Vergata Foundation,Tor Vergata University,Rome,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Nicolini","sequence":"additional","affiliation":[{"name":"Unit of Hepatobiliary Surgery and Transplantation, Azienda Ospedaliero\u2010Universitaria Ospedali Riuniti,Polytechnic University of Marche,Torrette Ancona,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso W.","family":"Avolio","sequence":"additional","affiliation":[{"name":"Liver Unit, Department of Surgery, Agostino Gemelli Hospital,Catholic University of the Sacred Heart,Rome,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Mrzljak","sequence":"additional","affiliation":[{"name":"Liver Transplant Centre,Merkur University,Zagreb,Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Branislav","family":"Kocman","sequence":"additional","affiliation":[{"name":"Liver Transplant Centre,Merkur University,Zagreb,Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Agnes","sequence":"additional","affiliation":[{"name":"Liver Unit, Department of Surgery, Agostino Gemelli Hospital,Catholic University of the Sacred Heart,Rome,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Vivarelli","sequence":"additional","affiliation":[{"name":"Unit of Hepatobiliary Surgery and Transplantation, Azienda Ospedaliero\u2010Universitaria Ospedali Riuniti,Polytechnic University of Marche,Torrette Ancona,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Tisone","sequence":"additional","affiliation":[{"name":"Department of Transplant Surgery, Polyclinic Tor Vergata Foundation,Tor Vergata University,Rome,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"Otto","sequence":"additional","affiliation":[{"name":"Department of Transplantation and Hepatobiliary Surgery,University of Mainz,Mainz,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5069-2461","authenticated-orcid":false,"given":"Emmanuel","family":"Tsochatzis","sequence":"additional","affiliation":[{"name":"University College London Institute for Liver and Digestive Health and Royal Free Sheila Sherlock Liver Centre,Royal Free Hospital and University College London,London,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Organ Transplantation,Umberto I Hospital, Sapienza University,Rome,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Viveiros","sequence":"additional","affiliation":[{"name":"Department of Medicine I,Medical University Innsbruck,Innsbruck,Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Ciccarelli","sequence":"additional","affiliation":[{"name":"Starzl Abdominal Transplant Unit, P\u00f4le de Chirurgie Exp\u00e9rimentale et Transplantation, Institut de Recherche Exp\u00e9rimentale et Clinique,Universit\u00e9 Catholique de Louvain,Brussels,Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umberto","family":"Cillo","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology, and Gastroenterology,University of Padua,Padua,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Lerut","sequence":"additional","affiliation":[{"name":"Starzl Abdominal Transplant Unit, P\u00f4le de Chirurgie 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