Mitochondrial DNA Variants in Patients with Liver Injury Due to Anti-Tuberculosis Drugs.

ABSTRACT:

Background

Hepatotoxicity is the most severe adverse effect of anti-tuberculosis therapy. Isoniazid's metabolite hydrazine is a mitochondrial complex II inhibitor. We hypothesized that mitochondrial DNA variants are risk factors for drug-induced liver injury (DILI) due to isoniazid, rifampicin or pyrazinamide.

Methods

We obtained peripheral blood from tuberculosis (TB) patients before anti-TB therapy. A total of 38 patients developed DILI due to anti-TB drugs. We selected 38 patients with TB but without DILI as controls. Next-generation sequencing detected point mutations in the mitochondrial DNA genome. DILI was defined as ALT ≥5 times the upper limit of normal (ULN), or ALT ≥3 times the ULN with total bilirubin ≥2 times the ULN.

Results

In 38 patients with DILI, the

SUBMITTER: Lee LN 

PROVIDER: S-EPMC6723168 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature