Clinical and Genetic Risk Factors for Drug-Induced Liver Injury Associated with Anti-Tuberculosis Treatment-A Study from Patients of Portuguese Health Centers

• Tipo: Artigo em Revista Científica Internacional
• Data: 2022

Autores

Cavaco, MJ (Autor) Outra; Alcobia, C (Autor) Outra; Oliveiros, B (Autor) Outra; Mesquita, LA (Autor) Outra; Carvalho, A (Autor) Outra; Matos, F (Autor) Outra; Carvalho, JM (Autor) Outra; Villar, M (Autor) Outra; Duarte R (Autor) ICBAS; Mendes, J (Autor) Outra; Ribeiro, C (Autor) Outra; Cordeiro, CR (Autor) Outra; Regateiro, F (Autor) Outra; Silva, HC (Autor) Outra

Revista

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Título: JOURNAL OF PERSONALIZED MEDICINE

Vol. 28

Página Final: 790

ISSN: 2075-4426

Editora: MDPI

Indexação

ISI Web of Knowledge - 3 Citações

Scopus - 7 Citações

Outras Informações

ID Authenticus: P-00W-QTY

DOI: 10.3390/jpm12050790

Abstract (EN): Drug-induced liver injury (DILI) is an unpredictable and feared side effect of antituberculosis treatment (AT). The present study aimed to identify clinical and genetic variables associated with susceptibility to AT-associated hepatotoxicity in patients with pulmonary tuberculosis treated with a standard protocol. Of 233 patients enrolled, 90% prospectively, 103 developed liver injury: 37 with mild and 66 with severe phenotype (DILI). All patients with mild hepatitis had a RUCAM score >= 4 and all patients with DILI had a RUCAM score >= 6. Eight clinical variables and variants in six candidate genes were assessed. A logistic multivariate regression analysis identified four risk factors for AT-DILI: age >= 55 years (OR:3.67; 95% CI:1.82-7.41; p < 0.001), concomitant medication with other hepatotoxic drugs (OR:2.54; 95% CI:1.23-5.26; p = 0.012), NAT2 slow acetylator status (OR:2.46; 95% CE1.25-4.84; p = 0.009), and carriers of p.Va1444Ala variant for ABCB11 gene (OR:2.06; 95 degrees/00:1.02-4.17; p = 0.044). The statistical model explains 24.9% of the susceptibility to AT-DILL with an 8.9 times difference between patients in the highest and in the lowest quartiles of risk scores. This study sustains the complex architecture of AT-DILI. Prospective studies should evaluate the benefit of NAT2 and ABCB11 genotyping in AT personalization, particularly in patients over 55 years.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 12