Evidence map›Paper›PMID 42768043›Full record

ArticleNature communications2026

Alcohol reshapes liver zonal plasticity and immune-metabolic reprogramming in metabolic-syndrome associated hepatocellular carcinoma.

Tian Tian, Yuhua Xue, Chunbao Sun, Lu Yang, Jinhui Wang, Brady Jin-Smith, Joshua M Barkin, Martin Nzegwu, Lin Jia, Huiping Zhou and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

25 authors.

Tian Tian *Department of Pathology, Tulane University, New Orleans, LA, USA.
Yuhua Xue *Department of Pathology, Tulane University, New Orleans, LA, USA.
Chunbao SunDepartment of Pathology, Tulane University, New Orleans, LA, USA.ORCID http://orcid.org/0000-0002-1376-4566
Lu YangDepartment of Systems Biology, Beckman Research Institute of the City of Hope, Duarte, CA, USA.ORCID http://orcid.org/0000-0001-7952-0399
Jinhui WangIntegrative Genomics Core, Beckman Research Institute of the City of Hope, Duarte, CA, USA.ORCID http://orcid.org/0000-0002-3499-4336
Brady Jin-SmithDepartment of Pathology, Tulane University, New Orleans, LA, USA.ORCID http://orcid.org/0009-0003-0653-7693
Joshua M BarkinDepartment of Pathology, Tulane University, New Orleans, LA, USA.ORCID http://orcid.org/0009-0009-9821-9935
Martin NzegwuDepartment of Pathology, Tulane University, New Orleans, LA, USA.
Lin JiaDepartment of Biological Sciences, The University of Texas at Dallas, Richardson, TX, USA.ORCID http://orcid.org/0000-0002-7653-7395
Huiping ZhouDepartment of Microbiology and Immunology, School of Medicine, Virginia Commonwealth University, and Richmond Veterans Medical Center, Richmond, VA, USA.ORCID http://orcid.org/0000-0002-0050-372X
Bilon KhambuDepartment of Pathology, Tulane University, New Orleans, LA, USA.ORCID http://orcid.org/0000-0002-9432-2064
Xiao-Ming YinDepartment of Pathology, Tulane University, New Orleans, LA, USA.ORCID http://orcid.org/0000-0002-8576-6093
Daohong ZhouDepartment of Biochemistry and Structural Biology, University of Texas Health Science Center, San Antonio, TX, USA.ORCID http://orcid.org/0000-0002-2400-6461
Anastasia G ChambersDepartment of Surgery, University of Florida Gainesville, Gainesville, FL, USA.ORCID http://orcid.org/0009-0003-3939-3569
Dongtao FuDepartment of Pathology, University of Florida Gainesville, Gainesville, FL, USA.
Zhen LinDepartment of Pathology, Tulane University, New Orleans, LA, USA.
Shengmin YanDepartment of Pathology, Tulane University, New Orleans, LA, USA.ORCID http://orcid.org/0000-0003-4012-9557
Lizi WuDepartment of Molecular Genetics & Microbiology, University of Florida Gainesville, Gainesville, FL, USA.ORCID http://orcid.org/0000-0002-0076-2617
Bryon PetersenDepartment of Pediatrics, University of Florida Gainesville, Gainesville, FL, USA.
Chenglong LiDepartment of Medicinal Chemistry, University of Florida Gainesville, Gainesville, FL, USA.
Li ZuoDepartment of Biochemistry, School of Basic Medical Science, Innovation and Entrepreneurship Laboratory for College Students, Anhui Medical University, Hefei, China.
Sergio DuarteDepartment of Surgery, University of Florida Gainesville, Gainesville, FL, USA.
Ali ZarrinparDepartment of Surgery, University of Florida Gainesville, Gainesville, FL, USA.ORCID http://orcid.org/0000-0002-6812-1816
Hua WangDepartment of Oncology, The First Affiliated Hospital of Anhui Medical University, Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, China.ORCID http://orcid.org/0000-0002-2605-5697
Liya PiDepartment of Pathology, Tulane University, New Orleans, LA, USA. lpi@tulane.edu.ORCID http://orcid.org/0000-0002-9868-7677

Funding

Regulation of the pro-fibrotic connective tissue growth factor in alcoholic liver disease: mechanisms and targeting approachesR01AA028035 · NIAAA · UNIVERSITY OF FLORIDA · PI PI, LIYA · 2020 to 2024
$1.7M
BLRD VA IK6 BX004477NIAAA NIH HHS R01 AA028035U.S. Department of Defense (United States Department of Defense) HT9425-23-1-0737U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA) NIAAA RO1AA028035
6 · The paper itself

Abstract

Hepatocellular carcinoma (HCC) commonly arises in metabolic dysfunction-associated steatohepatitis (MASH), alcohol-related liver disease (ALD), and metabolic dysfunction-associated ALD (MetALD), yet how zonal metabolic programs govern tumor lineage and immune responses remains unclear. Here, using complementary murine models of steatohepatitis-associated hepatocarcinogenesis, we show that CTNNB1-mutant MASH-HCC originates from periportal and midlobular hepatocytes through perivenous reprogramming. This transition is characterized by β-catenin activation, loss of periportal metabolic functions, and induction of the immunosuppressive IDO1-kynurenine-AhR axis. In contrast, ethanol exposure suppresses perivenous xenobiotic programs, destabilizes the β-catenin/AhR/CAR axis, and increases tumor heterogeneity by generating both progenitor/biliary- and hepatocyte-derived MetALD-HCC that remain sensitive to anti-programmed death-1 (aPD1) therapy. Pharmacologic AhR inhibition or hepatocyte-specific β-catenin deletion reduces MASH-HCC burden and restores sensitivity to aPD1 treatment. Together, these findings identify AhR as a central mediator of β-catenin-driven tumor immunosuppression and a potential therapeutic target in CTNNB1-mutant HCC, highlighting context-dependent mechanisms of immune escape in alcohol-associated HCC.

Indexed as

Carcinoma, HepatocellularEthanolLiverLiver NeoplasmsAnimalsbeta CateninDisease Models, AnimalHepatocytesHumansMaleMetabolic ReprogrammingMiceMice, Inbred C57BLbeta CateninCTNNB1 protein, mouseEthanol

Identifiers

PMID42768043
PMCPMC13594270

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.