Evidence map›Paper›PMID 21862974›Full record

ArticleThe pharmacogenomics journal2012

High plasma efavirenz level and CYP2B6*6 are associated with efavirenz-based HAART-induced liver injury in the treatment of naïve HIV patients from Ethiopia: a prospective cohort study.

G Yimer, W Amogne, A Habtewold, E Makonnen, N Ueda, A Suda, A Worku, W E Haefeli, J Burhenne, G Aderaye and 2 more

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Article in The pharmacogenomics journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed, 3 pooled it
5.2field-weighted citation impact, top 4% 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

64 citing papers in PubMed, 3 syntheses or guidelines pooled it, 121 citations in OpenAlex.

  1. Pooled it
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  17. Journal of personalized medicine · 2022
    Article
  18. Article
  19. Roles of Cofactors in Drug-Induced Liver Injury: Drug Metabolism and Beyond.Drug metabolism and disposition: the biological fate of chemicals · 2022
    Review
  20. Review

4 more citing papers are in PubMed but not listed here.

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 4 institutions in 3 countries.

G YimerDivision of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
W Amogne
A Habtewold
E Makonnen
N Ueda
A Suda
A Worku
W E Haefeli
J Burhenne
G Aderaye
L Lindquist
E Aklillu
Addis Ababa University · ETKarolinska Institutet · SEKarolinska University Hospital · SEHeidelberg University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The objective of this study was to assess the incidence, timing and identify pharmacogenetic, efavirenz (EFV) pharmacokinetic and biochemical predictors of EFV-based antiretroviral therapy (ART) drug-induced liver injury (DILI). ART-naïve HIV patients (n = 285) were prospectively enrolled. Pretreatment laboratory evaluations included hepatitis B surface antigen and C antibody, CD4 count and viral load. Liver tests were done at baseline, 1st, 2nd, 4th, 8th, 12th, 24th and 48th weeks during ART. Plasma EFV and 8-hydroxyefvairenz concentration was determined at week 4 using liquid chromatography-mass spectrometry. CYP2B6, CYP3A5, ABCB1 3435C/T and UGT2B7*2 genotyping was done using Taqman genotyping assay. Data were analyzed using survival analysis and Cox proportional hazards model. The incidence of DILI was 15.7% or 27.9 per 100 person-years and that of severe injury was 3.4% or 6.13 per 100 person-years. The median time for the development of DILI and severe injury was 2 and 4 weeks after initiation of ART, respectively. There was significant association of DILI with lower baseline platelet, albumin, log plasma viral load and CD4 count (P = 0.031, 0.037, 0.06 and 0.019, respectively). Elevated baseline alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, plasma EFV level and CYP2B6*6 were good predictors for the development of DILI (P = 0.03, 0.01, 0.016, 0.017 and 0.04, respectively). We report for the first time CYP2B6*6 as a putative genetic marker and high plasma EFV concentration as intermediate biomarker for vulnerability to EFV-induced liver injury in HIV patients. CYP2B6 genotyping and/or regular monitoring of EFV and lever enzymes level during early therapy is advised for early diagnosis and management of DILI.

Indexed as

AdultAlkynesAntiretroviral Therapy, Highly ActiveAryl Hydrocarbon HydroxylasesATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1BenzoxazinesChemical and Drug Induced Liver InjuryCohort StudiesCyclopropanesCytochrome P-450 CYP2B6Cytochrome P-450 CYP3AFemaleGenotypeHIV InfectionsHumans8-hydroxyefavirenzABCB1 protein, humanAlkynesAryl Hydrocarbon HydroxylasesATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1BenzoxazinesCyclopropanesCYP2B6 protein, humanCYP3A5 protein, humanCytochrome P-450 CYP2B6Cytochrome P-450 CYP3AefavirenzOxidoreductases, N-Demethylating

Identifiers

PMID21862974
OpenAlexW2078584349

What OpenQuestion holds

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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.