Evidence map›Paper›PMID 38967582›Full record

ArticleHepatology communications2024

Clinical and genetic risk factors for progressive fibrosis in metabolic dysfunction-associated steatotic liver disease.

David E Kaplan, Craig C Teerlink, Tae-Hwi Schwantes-An, Trina M Norden-Krichmar, Scott L DuVall, Timothy R Morgan, Philip S Tsao, Benjamin F Voight, Julie A Lynch, Marijana Vujković and 1 more

Abstract read
In one paragraph

Article in Hepatology communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 2 pooled it
–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

11 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Clinical Outcomes and Non-Invasive Testing in Metabolic Dysfunction-Associated Steatohepatitis With Cirrhosis: A Systematic Review.Liver international : official journal of the International Association for the Study of the Liver · 2026
    Pooled it
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  11. Impact of genotyping (Frontiers in endocrinology · 2025
    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

11 authors.

David E KaplanDepartment of Medicine, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA.ORCID 0000-0002-3839-336
Craig C TeerlinkVA Informatics and Computing Infrastructure (VINCI), VA Salt Lake City Health Care System, Salt Lake City, Utah, USA.ORCID 0000-0002-1992-2326
Tae-Hwi Schwantes-AnDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.ORCID 0000-0001-6387-0095
Trina M Norden-KrichmarDepartment of Medicine, Gastroenterology Section, Veterans Affairs Long Beach Healthcare System, Long Beach, California, USA.ORCID 0000-0002-0199-9915
Scott L DuVallVA Informatics and Computing Infrastructure (VINCI), VA Salt Lake City Health Care System, Salt Lake City, Utah, USA.ORCID 0000-0002-4898-3865
Timothy R MorganDepartment of Medicine, Gastroenterology Section, Veterans Affairs Long Beach Healthcare System, Long Beach, California, USA.ORCID 0000-0003-1328-0307
Philip S TsaoPalo Alto Epidemiology Research and Information Center for Genomics, VA Palo Alto, Palo Alto, California, USA.ORCID 0000-0001-7274-9318
Benjamin F VoightDepartment of Medicine, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA.ORCID 0000-0002-6205-9994
Julie A LynchVA Informatics and Computing Infrastructure (VINCI), VA Salt Lake City Health Care System, Salt Lake City, Utah, USA.ORCID 0000-0003-0108-2127
Marijana VujkovićDepartment of Medicine, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA.ORCID 0000-0003-4924-5714
Kyong-Mi ChangDepartment of Medicine, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA.ORCID 0000-0001-6811-9364

Funding

Functional Interrogation of T2D-associated genes in human stem cell-derived models and miceUM1DK126194 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI GRANT, STRUAN F A, KAESTNER, KLAUS H · 2020 to 2024
$8.8M
A genomics-based strategy to precision phenotyping and drug repositioning in cardiometabolic diseasesR01DK134575 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Marijana Vujkovic · 2023 to 2026
$1.4M
Genetics of Cardiometabolic Diseases in the VA PopulationI01BX003362 · VA · VETERANS ADMIN PALO ALTO HEALTH CARE SYS · PI Kyong-Mi Chang, Philip S Tsao · 2017 to 2026
–
Effect of simvastatin on hepatic decompensation and death in subjects with high-risk compensated cirrhosisI01CX002010 · VA · PHILADELPHIA VA MEDICAL CENTER · PI David E Kaplan, Tamar Taddei · 2020 to 2026
–
BLRD VA I01 BX003362CSRD VA I01 CX002010NIDDK NIH HHS R01 DK134575NIDDK NIH HHS UM1 DK126194
6 · The paper itself

Abstract

backgroundFibrosis-4 (FIB4) is a recommended noninvasive test to assess hepatic fibrosis among patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we used FIB4 trajectory over time (ie, "slope" of FIB4) as a surrogate marker of liver fibrosis progression and examined if FIB4 slope is associated with clinical and genetic factors among individuals with clinically defined MASLD within the Million Veteran Program Cohort.

methodsIn this retrospective cohort study, FIB4 slopes were estimated through linear regression for participants with clinically defined MASLD and FIB4 <2.67 at baseline. FIB4 slope was correlated with demographic parameters and clinical outcomes using logistic regression and Cox proportional hazard models. FIB4 slope as a quantitative phenotype was used in a genome-wide association analysis in ancestry-specific analysis and multiancestry meta-analysis using METAL.

resultsFIB4 slopes, generated from 98,361 subjects with MASLD (16,045 African, 74,320 European, and 7996 Hispanic), showed significant associations with sex, ancestry, and cardiometabolic risk factors (p < 0.05). FIB4 slopes also correlated strongly with hepatic outcomes and were independently associated with time to cirrhosis. Five genetic loci showed genome-wide significant associations (p < 5 × 10-8) with FIB4 slope among European ancestry subjects, including 2 known (PNPLA3 and TM6SF2) and 3 novel loci (TERT 5.1 × 10-11; LINC01088, 3.9 × 10-8; and MRC1, 2.9 × 10-9).

conclusionsLinear trajectories of FIB4 correlated significantly with time to progression to cirrhosis, with liver-related outcomes among individuals with MASLD and with known and novel genetic loci. FIB4 slope may be useful as a surrogate measure of fibrosis progression.

Indexed as

Disease ProgressionGenome-Wide Association StudyLiver CirrhosisAcyltransferasesAgedBiomarkersFatty LiverFemaleHumansMaleMembrane ProteinsMiddle AgedNon-alcoholic Fatty Liver DiseasePhospholipases A2, Calcium-IndependentRetrospective StudiesRisk FactorsAcyltransferasesBiomarkersMembrane ProteinsPhospholipases A2, Calcium-IndependentPNPLA3 protein, humanTM6SF2 protein, human

Identifiers

PMID38967582
PMCPMC11227360

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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.