Evidence map›Paper›PMID 35905417›Full record

ArticleClinical and translational gastroenterology2022

Whole Exome Sequencing Reveals Genetic Variants in HLA Class II Genes Associated With Transplant-free Survival of Indeterminate Acute Liver Failure.

Tsung-Jen Liao, Bohu Pan, Huixiao Hong, Paul Hayashi, Jody A Rule, Daniel Ganger, William M Lee, Jorge Rakela, Minjun Chen

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

Article in Clinical and translational gastroenterology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.4field-weighted citation impact, top 41% 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

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Genetic Variants of GBP4: Reduced Risks for Drug-Induced Acute Liver Failure in Non-Finnish European Population.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Article
  2. Article
  3. 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

9 authors at 6 institutions in 1 country.

Tsung-Jen LiaoDivision of Bioinformatics and Biostatistics, U.S. Food and Drug Administration (FDA) National Center for Toxicological Research, Jefferson, Arkansas, USA.
Bohu PanDivision of Bioinformatics and Biostatistics, U.S. Food and Drug Administration (FDA) National Center for Toxicological Research, Jefferson, Arkansas, USA.
Huixiao HongDivision of Bioinformatics and Biostatistics, U.S. Food and Drug Administration (FDA) National Center for Toxicological Research, Jefferson, Arkansas, USA.
Paul HayashiDivision of Hepatology and Nutrition, Office of New Drugs, FDA Center for Drug Evaluation and Research, Silver Spring, Maryland, USA.
Jody A RuleDivision of Gastroenterology and Hepatology, University of Texas Southwestern, Dallas, Texas, USA.
Daniel GangerDivision of Gastroenterology and Hepatology, Northwestern University, Chicago, Illinois, USA.
William M LeeDivision of Gastroenterology and Hepatology, University of Texas Southwestern, Dallas, Texas, USA.
Jorge RakelaDivision of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, Arizona, USA.
Minjun ChenDivision of Bioinformatics and Biostatistics, U.S. Food and Drug Administration (FDA) National Center for Toxicological Research, Jefferson, Arkansas, USA.
National Center for Toxicological Research · USThe University of Texas Southwestern Medical Center · USUnited States Food and Drug Administration · USCenter for Drug Evaluation and Research · USMayo Clinic in Florida · USNorthwestern University · US

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
NIDDK NIH HHS R01 DK058369NIDDK NIH HHS U01 DK058369
6 · The paper itself

Abstract

introductionIndeterminate acute liver failure (IND-ALF) is a rare clinical syndrome with a high mortality rate. Lacking a known etiology makes rapid evaluation and treatment difficult, with liver transplantation often considered as the only therapeutic option. Our aim was to identify genetic variants from whole exome sequencing data that might be associated with IND-ALF clinical outcomes.

methodsBioinformatics analysis was performed on whole exome sequencing data for 22 patients with IND-ALF. A 2-tier approach was used to identify significant single-nucleotide polymorphisms (SNPs) associated with IND-ALF clinical outcomes. Tier 1 identified the SNPs with a higher relative risk in the IND-ALF population compared with those identified in control populations. Tier 2 determined the SNPs connected to transplant-free survival and associated with model for end-stage liver disease serum sodium and Acute Liver Failure Study Group prognostic scores.

resultsThirty-one SNPs were found associated with a higher relative risk in the IND-ALF population compared with those in controls, of which 11 belong to the human leukocyte antigen (HLA) class II genes but none for the class I. Further analysis showed that 5 SNPs: rs796202376, rs139189937, and rs113473719 of HLA-DRB5; rs9272712 of HLA-DQA1; and rs747397929 of IDO1 were associated with a higher probability of IND-ALF transplant-free survival. Using 3 selected SNPs, a model for the polygenic risk score was developed to predict IND-ALF prognoses, which are comparable with those by model for end-stage liver disease serum sodium and Acute Liver Failure Study Group prognostic scores. DISCUSSION: Certain gene variants in HLA-DRB5, HLA-DQA1, and IDO1 were found associated with IND-ALF transplant-free survival. Once validated, these identified SNPs may help elucidate the mechanism of IND-ALF and assist in its diagnosis and management.

Indexed as

End Stage Liver DiseaseLiver Failure, AcuteExome SequencingGenes, MHC Class IIHLA-DRB5 ChainsHumansSeverity of Illness IndexSodiumHLA-DRB5 ChainsSodium

Identifiers

PMID35905417
PMCPMC10476814
OpenAlexW4281693560

What OpenQuestion holds

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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.