Evidence map›Paper›PMID 31279903›Full record

ArticleJournal of hepatology2019

ALDH2 deficiency promotes alcohol-associated liver cancer by activating oncogenic pathways via oxidized DNA-enriched extracellular vesicles.

Wonhyo Seo, Yanhang Gao, Yong He, Jing Sun, Hongqin Xu, Dechun Feng, Seol Hee Park, Young-Eun Cho, Adrien Guillot, Tianyi Ren and 8 more

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

Article in Journal of hepatology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
134citing papers in PubMed, 1 pooled it
12.3field-weighted citation impact, top 1% 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

134 citing papers in PubMed, 1 synthesis or guideline pooled it, 199 citations in OpenAlex.

  1. Pooled it
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  14. The metastasis landscape ofFrontiers in immunology · 2026
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74 more citing papers are in PubMed but not listed here.

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

18 authors at 5 institutions in 2 countries.

Wonhyo SeoLaboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA.
Yanhang GaoLaboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA; Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun 130021, China.
Yong HeLaboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA.
Jing SunDepartment of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun 130021, China.
Hongqin XuDepartment of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun 130021, China.
Dechun FengLaboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA.
Seol Hee ParkLaboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA.
Young-Eun ChoSection of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA.
Adrien GuillotLaboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA.
Tianyi RenLaboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA.
Ruihong WuDepartment of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun 130021, China.
Jingyun WangDepartment of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun 130021, China.
Seung-Jin KimLaboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA.
Seonghwan HwangLaboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA.
Suthat LiangpunsakulDivision of Gastroenterology and Hepatology, Department of Medicine, USA; Department of Biochemistry and Molecular Biology, Indiana University, Indianapolis, IN, USA; Roudebush Veterans Administration Medical Center, Indianapolis, IN, USA.
Yingzi YangDepartment of Developmental Biology, Harvard School of Dental Medicine, Boston, MA, USA.
Junqi NiuDepartment of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun 130021, China.
Bin GaoLaboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: bgao@mail.nih.gov.
National Institute on Alcohol Abuse and Alcoholism · USJilin University · CNNational Institutes of Health · USHarvard University · USIndiana University – Purdue University Indianapolis · US

Funding

Pathogenesis and Novel Therapeutic Targets of Steatotic Liver Disease and CancerZIAAA000369 · NIAAA · NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM · PI GAO, BIN · 2009 to 2025
$23.4M
Alcohol Metabolism, Functional Consequences, Apoptosis Signaling Pathways, and Organ DamageZIAAA000036 · NIAAA · NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM · PI SONG, BYOUNG-JOON · 2009 to 2025
$14.8M
Cellular and molecular mechanism of Hippo signaling in suppressing liver tumor formationR01CA222571 · NCI · HARVARD MEDICAL SCHOOL · PI YANG, YINGZI · 2018 to 2022
$1.9M
Intramural NIH HHS ZIA AA000369NCI NIH HHS R01 CA222571
6 · The paper itself

Abstract

BACKGROUND &

aimsExcessive alcohol consumption is one of the major causes of hepatocellular carcinoma (HCC). Approximately 30-40% of the Asian population are deficient for aldehyde dehydrogenase 2 (ALDH2), a key enzyme that detoxifies the ethanol metabolite acetaldehyde. However, how ALDH2 deficiency affects alcohol-related HCC remains unclear.

methodsALDH2 polymorphisms were studied in 646 patients with viral hepatitis B (HBV) infection, who did or did not drink alcohol. A new model of HCC induced by chronic carbon tetrachloride (CCl

resultsWe demonstrated that ALDH2 deficiency was not associated with liver disease progression but was associated with an increased risk of HCC development in cirrhotic patients with HBV who consumed excessive alcohol. The mechanisms underlying HCC development associated with cirrhosis and alcohol consumption were studied in Aldh2-deficient mice. We found that all 3 lines of Aldh2-deficient mice were more susceptible to CCl

conclusionsALDH2 deficiency is associated with an increased risk of alcohol-related HCC development from fibrosis in patients and in mice. Mechanistic studies reveal a novel mechanism that Aldh2-deficient hepatocytes promote alcohol-associated HCC by transferring harmful oxidized mitochondrial DNA-enriched extracellular vesicles into HCC and subsequently activating multiple oncogenic pathways in HCC. LAY SUMMARY: Alcoholics with an ALDH2 polymorphism have an increased risk of digestive tract cancer development, however, the link between ALDH2 deficiency and hepatocellular carcinoma (HCC) development has not been well established. In this study, we show that ALDH2 deficiency exacerbates alcohol-associated HCC development both in patients and mouse models. Mechanistic studies revealed that after chronic alcohol exposure, Aldh2-deficient hepatocytes produce a large amount of harmful oxidized mitochondrial DNA via extracellular vesicles, which can be delivered into neighboring HCC cells and subsequently activate multiple oncogenic pathways, promoting HCC.

Indexed as

AdultAlcohol DrinkingAlcoholismAldehyde Dehydrogenase, MitochondrialAnimalsCarbon TetrachlorideCarcinogenesisCarcinoma, HepatocellularCohort StudiesDisease Models, AnimalDNA, MitochondrialExtracellular VesiclesFemaleHepatitis B, ChronicHepatitis B virusHepatocytesAldehyde Dehydrogenase, MitochondrialALDH2 protein, humanALDH2 protein, mouseCarbon TetrachlorideDNA, MitochondrialAcetaldehydeAldehyde dehydrogenase 2CirrhosisEthanolExtracellular vesiclesHBVHepatocellular carcinomaTAZ

Identifiers

PMID31279903
PMCPMC6801025
OpenAlexW2954123950

What OpenQuestion holds

Textmetadata
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Read underepoch 390

Registered trials

None linked

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.