Pegvisomant-induced liver injury is related to the UGT1A1*28 polymorphism of Gilbert's syndrome.
J Clin Endocrinol Metab
; 95(5): 2147-54, 2010 May.
Article
en En
| MEDLINE
| ID: mdl-20207827
ABSTRACT
CONTEXT Pegvisomant (PEG) therapy has been associated with drug-induced liver dysfunction in acromegalic patients. The mechanism of its toxicity remains unknown. OBJECTIVE:
The primary objective was to determine whether or not the UGT1A1*28 polymorphism associated with Gilbert's syndrome influences the development of liver dysfunction during PEG treatment. DESIGN ANDSETTING:
A cross-sectional study was conducted in four Spanish university hospitals. PATIENTS Thirty-six acromegalic patients with active disease, resistant to somatostatin analogs, participated.RESULTS:
The prevalence of the UGT1A1*28 homozygous and heterozygous genotypes in acromegalic patients was 14 and 44%, respectively. Ten patients (28%) developed liver function test (LFT) abnormalities. There was a tendency for more frequent liver function abnormalities in males (70% males vs. 30% females, P = 0.058). Carriers of the UGT1A1*28 polymorphism had a higher incidence of LFT abnormalities than the UGT1A1 wild type (43% carriers vs. 7% wild type, P = 0.024). This difference persisted when adjusted in an all-factors multiple regression analysis [coefficient of determination (R(2)) = 0.463; P = 0.008] for age, gender, alcohol consumption, and UGT1A1*28 polymorphism. A stepwise multivariate likelihood binary logistic regression analysis (R(2) = 0.40; P = 0.003) identified male gender (beta = 7.21; P = 0.033) and UGT1A1*28 polymorphism (beta = 14.1; P = 0.028) as the only significant predictors for the development of LFT abnormalities.CONCLUSIONS:
The UGT1A1*28 genotype and male gender predict an increased incidence of LFT abnormalities during PEG therapy in acromegaly.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Acromegalia
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Glucuronosiltransferasa
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Hormona de Crecimiento Humana
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Enfermedad de Gilbert
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Hepatopatías
Tipo de estudio:
Clinical_trials
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Diagnostic_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Clin Endocrinol Metab
Año:
2010
Tipo del documento:
Article
País de afiliación:
España