Evidence map›Paper›PMID 39868816›Full record

ArticleLiver international : official journal of the International Association for the Study of the Liver2025

Genetic Variants of GBP4: Reduced Risks for Drug-Induced Acute Liver Failure in Non-Finnish European Population.

Tsung-Jen Liao, Menghang Xia, Paul Hayashi, Bohun Pan, Guruprasad P Aithal, M Isabel Lucena, Raúl J Andrade, Jody A Rule, William M Lee, Jorge Rakela and 2 more

Abstract read
In one paragraph

Article in Liver international : official journal of the International Association for the Study of the Liver, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. [Research progress in the field of drug-induced liver injury in 2025].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026
    Review
  2. 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.

Tsung-Jen LiaoDivision of Bioinformatics and Statistics, The FDA's National Center for Toxicological Research, Jefferson, Arkansas, USA.
Menghang XiaDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, USA.
Paul HayashiDivision of Hepatology and Nutrition, Office of New Drugs, FDA Center for Drug Evaluation and Research, Silver Spring, Maryland, USA.
Bohun PanDivision of Bioinformatics and Statistics, The FDA's National Center for Toxicological Research, Jefferson, Arkansas, USA.
Guruprasad P AithalNational Institute for Health Research (NIHR) Nottingham Biomedical Research Center at the Nottingham University Hospital, NHS Trust and University of Nottingham, Nottingham, UK.ORCID 0000-0003-3924-4830
M Isabel LucenaServicios de Aparato Digestivo y de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga IBIMA_Plataforma Bionand, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain.ORCID 0000-0001-9586-4896
Raúl J AndradeServicios de Aparato Digestivo y de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga IBIMA_Plataforma Bionand, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain.ORCID 0000-0002-1565-0757
Jody A RuleDivision of Gastroenterology and Hepatology, University of Texas Southwestern, Dallas, Texas, USA.ORCID 0000-0002-4019-372X
William M LeeDivision of Gastroenterology and Hepatology, University of Texas Southwestern, Dallas, Texas, USA.ORCID 0000-0002-2783-5441
Jorge RakelaDivision of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, Arizona, USA.
Ruili HuangDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, USA.
Minjun ChenDivision of Bioinformatics and Statistics, The FDA's National Center for Toxicological Research, Jefferson, Arkansas, USA.ORCID 0000-0002-6453-2351

Funding

A Multi-Center Study of Acute Liver Failure in AdultsU01DK058369 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI DURKALSKI, VALERIE L, FONTANA, ROBERT J · 2005 to 2019
$27.4M
A MULTI-CENTER THERAPY TRIAL FOR ACUTE LIVER FAILURER01DK058369 · NIDDK · UNIVERSITY OF TEXAS SW MED CTR/DALLAS · PI LEE, WILLIAM M · 2000 to 2004
$4.2M
FDA's Office of Women HealthIntramural FDA HHS FD999999National Center for Advancing Translational Sciences of National Institutes of HealthNIDDK NIH HHS R01 DK058369NIDDK NIH HHS U01 DK058369
6 · The paper itself

Abstract

BACKGROUND AND

aimsAcute liver failure (ALF) is a serious condition, typically in individuals without prior liver disease. Drug-induced ALF (DIALF) constitutes a major portion of ALF cases. Our research aimed to identify potential genetic predispositions to DIALF.

methodsWe analysed the potential genetic variants associated with DIALF using the whole exome sequencing data from 75 cases, including 40 non-Finnish European cases in the pilot study. Chi-square tests were performed for case-control analysis against the 1000 genomes project as the control. A replication study of 44 DIALF cases that included 24 non-Finnish Europeans was conducted to validate candidate variants. The association between clinical phenotype and genotypes was analysed using one-way analysis of variance.

resultsEight variants (rs561037, rs561042, rs608339, rs655260, rs1142886, rs1142888, rs1142889 and rs1142890) in the guanylate binding protein 4 (GBP4) were significantly associated with DIALF in non-Finnish Europeans in the pilot study and confirmed in the replication study. Rs561037 and rs561042 were highly significant with the lowest allele frequencies in both pilot and replication studies. An association was also found between these variants and milder clinical outcomes, indicated by lower peak levels of ALT, AST and higher Karnofsky performance scores.

conclusionOur study identified eight GBP4 missense variants linked to a lower risk of DIALF in the non-Finnish European population. The GBP4 protein, activated by interferon-gamma, plays a critical role in innate immunity. These findings suggest that GBP4 variants might influence immune and inflammatory responses in DIALF, though further studies are needed to elucidate the underlying mechanisms.

Indexed as

Chemical and Drug Induced Liver InjuryGTP-Binding ProteinsLiver Failure, AcuteAdultCase-Control StudiesEuropeExome SequencingFemaleGenetic Predisposition to DiseaseGenotypeHumansMaleMiddle AgedPilot ProjectsPolymorphism, Single NucleotideWhite PeopleGTP-Binding Proteinsdrug‐induced acute liver failureGBP4genetic risk factorIFN‐γ signalling

Identifiers

PMID39868816
PMCPMC11850085

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Registered trials

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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.