Evidence map›Paper›PMID 31412578›Full record

ArticleJournal of clinical medicine2019

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

Li-Na Lee, Chun-Ta Huang, Chia-Lin Hsu, Hsiu-Ching Chang, I-Shiow Jan, Jia-Luen Liu, Jin-Chuan Sheu, Jann-Tay Wang, Wei-Lun Liu, Huei-Shu Wu and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of clinical medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
2.5field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. MitochondrialInternational journal of molecular sciences · 2025
    Article
  5. Article
  6. Review
  7. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 1 country.

Li-Na LeeDepartment of Laboratory Medicine, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei City 24352, Taiwan.
Chun-Ta HuangDepartment of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan.ORCID 0000-0002-5234-4986
Chia-Lin HsuDepartment of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan.
Hsiu-Ching ChangDepartment of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan.
I-Shiow JanDepartment of Laboratory Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan.
Jia-Luen LiuOne-Star Technology, New Taipei City 24352, Taiwan.
Jin-Chuan SheuDepartment of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan.
Jann-Tay WangDepartment of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan.
Wei-Lun LiuSchool of Medicine, College of Medicine, Fu Jen Catholic University, and Department of Emergency and Critical Care Medicine, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei City 24205, Taiwan.ORCID 0000-0001-8593-8492
Huei-Shu WuDepartment of Laboratory Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan.
Ching-Nien ChangDepartment of Surgery, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei City 24352, Taiwan.
Jann-Yuan WangDepartment of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan. jywang@ntu.edu.tw.ORCID 0000-0003-3406-366X
National Taiwan University Hospital · TWFu Jen Catholic University · TWLite-On Technology Corporation (Taiwan) · TW

Funding

Ministry of Health and Welfare, Taiwan 104-2629-B-002-001
6 · The paper itself

Abstract

backgroundHepatotoxicity 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.

methodsWe 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.

resultsIn 38 patients with DILI, the causative drug was isoniazid in eight, rifampicin in 14 and pyrazinamide in 16. Patients with isoniazid-induced liver injury had more variants in complex I's NADH subunit 5 and 1 genes, more nonsynonymous mutations in NADH subunit 5, and a higher ratio of nonsynonymous to total substitutions. Patients with rifampicin- or pyrazinamide-induced liver injury had no association with mitochondrial DNA variants.

conclusionsVariants in complex I's subunit 1 and 5 genes might affect respiratory chain function and predispose isoniazid-induced liver injury when exposed to hydrazine, a metabolite of isoniazid and a complex II inhibitor.

Indexed as

complex IDNA variantsDrug-induced liver injurymitochondriatuberculosis

Identifiers

PMID31412578
PMCPMC6723168
OpenAlexW2966949321

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.