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

• Type: Article in International Scientific Journal
• Date: 2022

Authors

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

Journal

The Journal is awaiting validation by the Administrative Services.

Title: JOURNAL OF PERSONALIZED MEDICINE

Vol. 28

Final page: 790

ISSN: 2075-4426

Publisher: MDPI

Indexing

ISI Web of Knowledge - 3 Citations

Scopus - 7 Citations

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12