Evidence map›Paper›PMID 41514510›Full record

ArticleLiver international : official journal of the International Association for the Study of the Liver2026

Evaluation of Pathogenic Variants Associated With Monogenic Disorders of Dyslipidemia in Patients With Well Characterised MASLD.

Tae-Hwi Schwantes-An, Marco A Abreu, Brent A Neuschwander-Tetri, Jian Wang, Xiuqing Guo, Jingyi Tan, Robert A Hegele, Nicholas O Davidson, Luca Lotta, Niek Verweij and 3 more

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In one paragraph

Article in Liver international : official journal of the International Association for the Study of the Liver, 2026. 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. Review
  2. Evaluation of Pathogenic Variants Associated With Monogenic Disorders of Dyslipidemia in Patients With Well Characterised MASLD.Liver international : official journal of the International Association for the Study of the Liver · 2026
    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

13 authors.

Tae-Hwi Schwantes-AnDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Marco A AbreuDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Brent A Neuschwander-TetriDivision of Gastroenterology and Hepatology, Saint Louis University, St Louis, Missouri, USA.
Jian WangRobarts Research Institute, Schulich School of Medicine & Dentistry, Western University, 1151 Richmond St, London, Ontario, Canada.
Xiuqing GuoInstitute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, USA.
Jingyi TanInstitute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, USA.
Robert A HegeleRobarts Research Institute, Schulich School of Medicine & Dentistry, Western University, 1151 Richmond St, London, Ontario, Canada.ORCID 0000-0003-2861-5325
Nicholas O DavidsonDivision of Gastroenterology, Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA.
Luca LottaRegeneron Genetics Center, Regeneron Pharmaceuticals, Tarrytown, New York, USA.
Niek VerweijRegeneron Genetics Center, Regeneron Pharmaceuticals, Tarrytown, New York, USA.
Katherine P YatesDepartment of Epidemiology and Biostatistics, Johns Hopkins University, Baltimore, Maryland, USA.
Jerome I RotterInstitute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, USA.
Naga ChalasaniDivision of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.

Funding

Non Alcoholic Steatohepatitis Clinical Research NetworkU01DK061732 · NIDDK · CLEVELAND CLINIC LERNER COM-CWRU · PI Srinivasan Dasarathy · 2002 to 2026
$12.2M
VEDS Year2-Continuation of the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Data Coordinating CenterU24DK061730 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI JEANNE M CLARK, David M Shade · 2019 to 2026
$11.3M
Collaborative Clinical Research on Non Alcoholic StratohepatitisU01DK061737 · NIDDK · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI NAGA P CHALASANI · 2002 to 2026
$10.2M
Impaired VLDL secretion, progression and reversal of hepatic fibrogenesisR01DK119437 · NIDDK · WASHINGTON UNIVERSITY · PI Nicholas O. Davidson · 2019 to 2026
$3.8M
NIDDK NIH HHS R01 DK119437NIDDK NIH HHS U01 DK061732NIDDK NIH HHS U01 DK061737NIDDK NIH HHS U24 DK061730
6 · The paper itself

Abstract

BACKGROUND AND

aimsDyslipidemia is common in patients with MASLD, but the frequency and significance of inherited disorders of dyslipidemia are unclear. We investigated the prevalence and significance of pathogenic variants associated with selected monogenic disorders of dyslipidemia in 3358 patients with well-characterised MASLD. APPROACH: We identified clinically relevant variants in APOB, MTTP, PCSK9, ANGPTL3, LDLR and LDLRAP1 genes which can cause hypobetalipoproteinemia (HBL) and familial hypercholesterolemia (FH). Using ClinVar annotations as initial variant selection, we identified 2027 variants in those 6 genes which are reported as 'pathogenic' or 'likely pathogenic' (P/LP). We first assessed for the presence of P/LP variants in the study cohort and then investigated the effect of carrying P/LP variants on liver histology, by comparing ~4 matched controls for each APOB and LDLR carrier. As interpretative analyses, we also looked at the difference between liver enzymes, lipid measures and outcomes between the carriers and matched controls.

resultsTwenty-two variants among these 2027 P/LP variants were present in 24 out of 3358 patients (12 ApoB, 10 LDLR, 1 ANGPTL3 and 1 MTTP variant carriers). Compared to controls, APOB carriers had higher steatosis grade (2.4 vs. 1.7, p-value 0.0028), higher NAFLD activity score (NAS) (4.9 vs. 3.8, p-value 0.04), and numerically higher but statistically not significant fibrosis stage (1.2 vs. 1.1, p-value 0.75) and ALT (87.4 vs. 58.1 U/L, p-value 0.06). Their LDL-c (51 vs. 147.8 mg/dL, p-value 6.1E-09) and triglycerides (91.5 vs. 160.6 mg/dL, p-value 2.8E-03) were significantly lower. Compared to controls, LDLR carriers had numerically higher steatosis grade, NAS, fibrosis stage and LDL-c levels, but these were not statistically different.

conclusionsMonogenic disorders of dyslipidemia are rarely present in patients with MASLD and are sometimes associated with worse liver histology. Testing for these conditions may be considered on a case-by-case basis.

Indexed as

DyslipidemiasHyperlipoproteinemia Type IIAdaptor Proteins, Signal TransducingAdultAngiopoietin-Like Protein 3Angiopoietin-like ProteinsApolipoprotein B-100Carrier ProteinsCase-Control StudiesFemaleGenetic Predisposition to DiseaseHumansHypobetalipoproteinemiasLiverMaleMiddle AgedAdaptor Proteins, Signal TransducingAngiopoietin-Like Protein 3Angiopoietin-like ProteinsANGPTL3 protein, humanAPOB protein, humanApolipoprotein B-100Carrier ProteinsLDLRAP1 protein, humanLDLR protein, humanmicrosomal triglyceride transfer proteinPCSK9 protein, humanProprotein Convertase 9Receptors, LDLAPOBhereditary dyslipidemiahistological progressionLDLRMASLD

Identifiers

PMID41514510
PMCPMC12789714

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Texttitle and abstract
LicenceCC BY
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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.