CYP2E1 genotype and isoniazid-induced hepatotoxicity in patients treated for latent tuberculosis

Vuilleumier, Nicolas; Rossier, Michel F; Chiappe, Alberto; Degoumois, Florence; Dayer, Pierre; Mermillod, Bernadette; Nicod, Laurent; Desmeules, Jules; Hochstrasser, Denis (2006). CYP2E1 genotype and isoniazid-induced hepatotoxicity in patients treated for latent tuberculosis. European journal of clinical pharmacology, 62(6), pp. 423-9. Berlin: Springer 10.1080/00365510260389976

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OBJECTIVE: To determine whether pharmacogenetic tests such as N-acetyltransferase 2 (NAT2) and cytochrome P450 2E1 (CYP2E1) genotyping are useful in identifying patients prone to antituberculosis drug-induced hepatotoxicity in a cosmopolite population. METHODS: In a prospective study we genotyped 89 patients treated with isoniazid (INH) for latent tuberculosis. INH-induced hepatitis (INH-H) or elevated liver enzymes including hepatitis (INH-ELE) was diagnosed based on the clinical diagnostic scale (CDS) designed for routine clinical practice. NAT2 genotypes were assessed by fluorescence resonance energy transfer probe after PCR analysis, and CYP2E1 genotypes were determined by PCR with restriction fragment length polymorphism analysis. RESULTS: Twenty-six patients (29%) had INH-ELE, while eight (9%) presented with INH-H leading to INH treatment interruption. We report no significant influence of NAT2 polymorphism, but we did find a significant association between the CYP2E1 *1A/*1A genotype and INH-ELE (OR: 3.4; 95% CI:1.1-12; p = 0.02) and a non significant trend for INH-H (OR: 5.9; 95% CI: 0.69-270; p = 0.13) compared with other CYP2E1 genotypes. This test for predicting INH-ELE had a positive predictive value (PPV) of 39% (95% CI: 26-54%) and a negative predictive value (NPV) of 84% (95% CI: 69-94%). CONCLUSION: The genotyping of CYP2E1 polymorphisms may be a useful predictive tool in the common setting of a highly heterogeneous population for predicting isoniazid-induced hepatic toxicity. Larger prospective randomized trials are needed to confirm these results.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology

UniBE Contributor:

Nicod, Laurent

ISSN:

0031-6970

ISBN:

16770646

Publisher:

Springer

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:48

Last Modified:

17 Mar 2015 21:49

Publisher DOI:

10.1080/00365510260389976

PubMed ID:

16770646

Web of Science ID:

000179228200003

URI:

https://boris.unibe.ch/id/eprint/20229 (FactScience: 3408)

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