{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T23:35:38Z","timestamp":1772580938413,"version":"3.50.1"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:sec><jats:title>Context<\/jats:title><jats:p>Hepatotoxicity is one of the most serious adverse effects in acromegalic patients treated with pegvisomant (PEG-V). Recent studies have found an association between this adverse event and the UGT1A1 allele 28 polymorphism associated with Gilbert's syndrome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine whether UGT1A1*28 and alcohol dehydrogenase (ADH) polymorphisms influence liver toxicity during PEG-V treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design and setting<\/jats:title><jats:p>Multicenter observational retrospective study conducted in 13 tertiary care endocrinology units in Italy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients<\/jats:title><jats:p>A total of 112 patients with active disease resistant to somatostatin analogs (SSTa) and 108 controls were enrolled.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interventions<\/jats:title><jats:p>Clinical and biochemical data were recorded by electronic clinical reporting forms. Blood or DNA samples were sent to the coordinating center for genotyping.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>No differences in genotypes between patients and controls were found. During PEG-V therapy liver function tests (LFT), abnormalities and overt hepatotoxicity developed in 17 and 4.5% of patients respectively. Logistic and linear regression analyses showed an association between LFT abnormalities during the follow-up visit and prior events of LFT abnormalities in medical history (odds ratio=1.25;<jats:italic>P<\/jats:italic>=0.04) and the number of concomitant medications, other than SSTa (<jats:italic>B<\/jats:italic>=3.9;<jats:italic>P<\/jats:italic>=0.03). No correlation between LFT alterations and UGT1A1 allele 28 as well as ADH1C and B polymorphisms was found.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>UGT1A1 allele 28 and ADH1C and B polymorphisms do not predict increased risk of hepatotoxicity during PEG-V therapy. Conversely, patients with multi-therapies and with previous episodes of liver disease should be carefully managed, due to the observed association between these conditions and LFT abnormalities during PEG-V therapy.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-13-0657","type":"journal-article","created":{"date-parts":[[2013,11,12]],"date-time":"2013-11-12T03:58:40Z","timestamp":1384228720000},"page":"247-254","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":14,"title":["Role of UGT1A1 and ADH gene polymorphisms in pegvisomant-induced liver toxicity in acromegalic patients"],"prefix":"10.1093","volume":"170","author":[{"given":"M","family":"Filopanti","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A M","family":"Barbieri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"Mantovani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Corbetta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V","family":"Gasco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Ragonese","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Martini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F","family":"Bogazzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Colao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D","family":"Ferone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Peri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F","family":"Pigliaru","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"Angeletti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Arosio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Beck-Peccoz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A G","family":"Lania","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Spada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","reference":[{"issue":"5","key":"1_17276444","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1210\/er.2001-0022","volume":"23","author":"Kopchick","year":"2002","journal-title":"Endocrine Reviews","ISSN":"https:\/\/id.crossref.org\/issn\/0163-769X","issn-type":"print"},{"issue":"3","key":"2_21655696","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1530\/eje.1.02112","volume":"154","author":"Colao","year":"2006","journal-title":"European Journal of Endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0804-4643","issn-type":"print"},{"issue":"1","key":"3_23507718","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1530\/eje.1.02312","volume":"156","author":"Schreiber","year":"2007","journal-title":"European Journal of Endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0804-4643","issn-type":"print"},{"issue":"16","key":"4_6544062","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1056\/NEJM200004203421604","volume":"342","author":"Trainer","year":"2000","journal-title":"New England Journal of Medicine","ISSN":"https:\/\/id.crossref.org\/issn\/0028-4793","issn-type":"print"},{"key":"5_42468798","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/nrendo.2011.42","volume":"7","year":"2011","journal-title":"NATURE REVIEWS ENDOCRINOLOGY"},{"key":"6_36912908","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/ncpendmet0831","volume":"4","year":"2008","journal-title":"NATURE CLINICAL PRACTICE ENDOCRINOLOGY METABOLISM"},{"issue":"5","key":"7_36732403","doi-asserted-by":"publisher","first-page":"2147","DOI":"10.1210\/jc.2009-2547","volume":"95","year":"2010","journal-title":"Journal of Clinical Endocrinology &amp; 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