Evidence map›Paper›PMID 24714066›Full record

Observational studyPloS one2014

Evaluation of patterns of liver toxicity in patients on antiretroviral and anti-tuberculosis drugs: a prospective four arm observational study in ethiopian patients.

Getnet Yimer, Marcus Gry, Wondwossen Amogne, Eyasu Makonnen, Abiy Habtewold, Zelalem Petros, Getachew Aderaye, Ina Schuppe-Koistinen, Lars Lindquist, Eleni Aklillu

Open access · goldAbstract readObservational Study
In one paragraph

Observational study in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 2 pooled it
6.9field-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

36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 68 citations in OpenAlex.

  1. Pooled it
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  5. A partially randomised trial of pretomanid, moxifloxacin and pyrazinamide for pulmonary TB.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2021
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  18. Journal of personalized medicine · 2022
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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

10 authors at 5 institutions in 2 countries.

Getnet YimerDivision of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge C1:68, Karolinska Institutet, Stockholm, Sweden; Department of Pharmacology, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
Marcus GryFormer AstraZeneca R&D, Global Safety Assessment, Molecular Toxicology, Södertälje, Sweden.
Wondwossen AmogneDepartment of Internal Medicine, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; Department of Medicine, Division of Infectious Diseases, Karolinska Institute at Karolinska University Hospital Huddinge I:73, Stockholm, Sweden.
Eyasu MakonnenDepartment of Pharmacology, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
Abiy HabtewoldDivision of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge C1:68, Karolinska Institutet, Stockholm, Sweden; Department of Pharmacology, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
Zelalem PetrosDepartment of Pharmacology, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
Getachew AderayeDepartment of Internal Medicine, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
Ina Schuppe-KoistinenAstraZeneca Innovative Medicines Personalised Healthcare & Biomarkers, Science for Life Laboratory, Solna, Sweden.
Lars LindquistDepartment of Medicine, Division of Infectious Diseases, Karolinska Institute at Karolinska University Hospital Huddinge I:73, Stockholm, Sweden.
Eleni AklilluDivision of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge C1:68, Karolinska Institutet, Stockholm, Sweden.
Addis Ababa University · ETKarolinska Institutet · SEKarolinska University Hospital · SEAstraZeneca (Sweden) · SEScience for Life Laboratory · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesTo evaluate the incidence, type, severity and predictors of antiretroviral and/or anti-tuberculosis drugs induced liver injury (DILI).

methodsA total of 1,060 treatment naive patients were prospectively enrolled into four treatment groups: HIV patients receiving efavirenz based HAART alone (Arm-1); TB-HIV co-infected patients with CD4≤200 cells/μL, receiving concomitant rifampicin based anti-TB and efavirenz based HAART (Arm-2); TB-HIV co-infected patients with CD4>200 cells/μL, receiving anti-TB alone (Arm-3); TB patients taking rifampicin based anti-TB alone (Arm-4). Liver enzyme levels were monitored at baseline, 1st, 2nd, 4th, 8th, 12th and 24th weeks during treatment. CD4 and HIV viral load was measured at baseline, 24th and 48th weeks. Data were analyzed using multivariate Cox Proportional Hazards Model.

resultsA total of 159 patients (15%) developed DILI with severity grades 1, 2, 3 and 4 of 53.5%, 32.7%, 11.3% and 2.5% respectively. The incidence of cholestatic, hepatocellular or mixed pattern was 61%, 15% and 24%, respectively. Incidence of DILI was highest in Arm-2 (24.2%)>Arm-3 (10.8%)>Arm-1 (8.8%)>Arm-4 (2.9%). Concomitant anti-TB-HIV therapy increased the risk of DILI by 10-fold than anti-TB alone (p<0.0001). HIV co-infection increased the risk of anti-TB DILI by 4-fold (p = 0.004). HAART associated DILI was 3-fold higher than anti-TB alone, (p = 0.02). HAART was associated with cholestatic and grade 1 DILI whereas anti-TB therapy was associated with hepatocellular and grade ≥ 2. Treatment type, lower CD4, platelet, hemoglobin, higher serum AST and direct bilirubin levels at baseline were significant DILI predictors. There was no effect of DILI on immunologic recovery or virologic suppression rate of HAART.

conclusionHAART associated DILI is mainly cholestatic and mild whereas hepatocellular or mixed pattern with high severity grade is more common in anti-tuberculosis DILI. TB-HIV co-infection, disease severity and concomitant treatment exacerbates the risk of DILI.

Indexed as

AdultAnti-Retroviral AgentsAntiretroviral Therapy, Highly ActiveAntitubercular AgentsChemical and Drug Induced Liver InjuryEthiopiaFemaleHIV InfectionsHumansIncidenceKaplan-Meier EstimateMalePrognosisProspective StudiesSeverity of Illness IndexTreatment OutcomeAnti-Retroviral AgentsAntitubercular Agents

Identifiers

PMID24714066
PMCPMC3979833
OpenAlexW2042036586

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.