Abstract Context: 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. Objective: To determine whether UGT1A1 28 and alcohol dehydrogenase (ADH) polymorphisms influence liver toxicity during PEG-V treatment. Design and setting: Multicenter observational retrospective study conducted in 13 tertiary care endocrinology units in Italy. Patients: A total of 112 patients with active disease resistant to somatostatin analogs (SSTa) and 108 controls were enrolled. Interventions: Clinical and biochemical data were recorded by electronic clinical reporting forms. Blood or DNA samples were sent to the coordinating center for genotyping. Results: No differences in genotypes between patients and controls were found. During PEG-V therapy liver function tests (LFT), abnormalitiesandoverthepatotoxicity developed in 17and4.5%ofpatients respectively. Logistic andlinear regressionanalyses showed an association between LFT abnormalities during the follow-up visit and prior events of LFT abnormalities in medical history (odds ratioZ1.25; PZ0.04) and the number of concomitant medications, other than SSTa (BZ3.9; PZ0.03). No correlation between LFT alterations and UGT1A1 allele 28 as well as ADH1C and B polymorphisms was found. Conclusions: 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.

Role of UGT1A1 and ADH gene polymorphisms in pegvisomant-induced liver toxicity in acromegalic patients / M. Filopanti, A.M. Barbieri, G. Mantovani, S. Corbetta, V. Gasco, M. Ragonese, C. Martini, F. Bogazzi, A. Colao, D. Ferone, A. Peri, F. Pigliaru, G. Angeletti, M. Arosio, P. Beck-Peccoz, A.G. Lania, A. Spada. - In: EUROPEAN JOURNAL OF ENDOCRINOLOGY. - ISSN 0804-4643. - 170:2(2014 Feb), pp. 249-256. [10.1530/EJE-13-0657]

Role of UGT1A1 and ADH gene polymorphisms in pegvisomant-induced liver toxicity in acromegalic patients

A.M. Barbieri;G. Mantovani;S. Corbetta;M. Arosio;P. Beck-Peccoz;A.G. Lania;A. Spada
2014-02

Abstract

Abstract Context: 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. Objective: To determine whether UGT1A1 28 and alcohol dehydrogenase (ADH) polymorphisms influence liver toxicity during PEG-V treatment. Design and setting: Multicenter observational retrospective study conducted in 13 tertiary care endocrinology units in Italy. Patients: A total of 112 patients with active disease resistant to somatostatin analogs (SSTa) and 108 controls were enrolled. Interventions: Clinical and biochemical data were recorded by electronic clinical reporting forms. Blood or DNA samples were sent to the coordinating center for genotyping. Results: No differences in genotypes between patients and controls were found. During PEG-V therapy liver function tests (LFT), abnormalitiesandoverthepatotoxicity developed in 17and4.5%ofpatients respectively. Logistic andlinear regressionanalyses showed an association between LFT abnormalities during the follow-up visit and prior events of LFT abnormalities in medical history (odds ratioZ1.25; PZ0.04) and the number of concomitant medications, other than SSTa (BZ3.9; PZ0.03). No correlation between LFT alterations and UGT1A1 allele 28 as well as ADH1C and B polymorphisms was found. Conclusions: 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.
Acromegaly ; Pegvisomant ; Liver toxicity
Settore MED/13 - Endocrinologia
Article (author)
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/232424
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 11
  • ???jsp.display-item.citation.isi??? 12
social impact