KEGG DISEASE: アルコール性肝疾患

DISEASE: アルコール性肝疾患

エントリ

H02516

名称

アルコール性肝疾患

概要

Alcoholic liver disease (ALD) refers to the damages to the liver and its functions due to alcohol overconsumption. It ranges from simple steatosis to steatohepatitis, cirrhosis, and even hepatocellular carcinoma. Alcohol consumption promotes liver inflammation by increasing the translocation of gut-derived endotoxins to the portal circulation and activating Kupffer cells to produce TNF-alpha through the LPS/Toll like receptor (TLR) 4 pathways. TNF-alpha induces hepatocellular damage. When alcohol intake is chronic and heavy, steatosis is caused via generation of acetaldehyde, reactive oxygen species (ROS) and ER stress. ROS inhibits key hepatic transcriptional regulators such as AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor alpha (PPAR-alpha), which are responsible for fatty acid oxidation and export via ACC and CPT-1. The blockade of AMPK also leads to overexpression of SREBP-1, resulting in an increase of de novo lipogenesis. Moreover, excessive intracellular ROS production induced by ethanol and its metabolite has a critical role in ethanol-induced apoptosis, which may be the critical process in the exacerbation of ALD. It is inferred that the apoptotic signal derived from ROS that was produced by NOX, is mainly transduced through the JNK and p38 MAPK pathways.

カテゴリ

消化器系疾患

階層分類

ICD-11 による疾患分類 [BR:jp08403]
13 消化器系の疾患
  肝疾患
   DB94  アルコール性肝疾患
    H02516  アルコール性肝疾患

疾患パスウェイ

hsa04936

アルコール性肝疾患

リンク

ICD-11:

DB94

MeSH:

D008108

文献

PMID:25782093

著者

Louvet A, Mathurin P

タイトル

Alcoholic liver disease: mechanisms of injury and targeted treatment.

雑誌

Nat Rev Gastroenterol Hepatol 12:231-42 (2015)
DOI:10.1038/nrgastro.2015.35

文献

PMID:24385684

著者

Kawaratani H, Tsujimoto T, Douhara A, Takaya H, Moriya K, Namisaki T, Noguchi R, Yoshiji H, Fujimoto M, Fukui H

タイトル

The effect of inflammatory cytokines in alcoholic liver disease.

雑誌

Mediators Inflamm 2013:495156 (2013)
DOI:10.1155/2013/495156

文献

PMID:28134813

著者

Magdaleno F, Blajszczak CC, Nieto N

タイトル

Key Events Participating in the Pathogenesis of Alcoholic Liver Disease.

雑誌

Biomolecules 7:E9 (2017)
DOI:10.3390/biom7010009

文献

PMID:21252049

著者

Gao B, Seki E, Brenner DA, Friedman S, Cohen JI, Nagy L, Szabo G, Zakhari S

タイトル

Innate immunity in alcoholic liver disease.

雑誌

Am J Physiol Gastrointest Liver Physiol 300:G516-25 (2011)
DOI:10.1152/ajpgi.00537.2010

文献

PMID:18709650

著者

Rogers CQ, Ajmo JM, You M

タイトル

Adiponectin and alcoholic fatty liver disease.

雑誌

IUBMB Life 60:790-7 (2008)
DOI:10.1002/iub.124

文献

PMID:26755857

著者

Kim MS, Ong M, Qu X

タイトル

Optimal management for alcoholic liver disease: Conventional medications, natural therapy or combination?

雑誌

World J Gastroenterol 22:8-23 (2016)
DOI:10.3748/wjg.v22.i1.8

文献

PMID:30115921

著者

Seitz HK, Bataller R, Cortez-Pinto H, Gao B, Gual A, Lackner C, Mathurin P, Mueller S, Szabo G, Tsukamoto H

タイトル

Alcoholic liver disease.

雑誌

Nat Rev Dis Primers 4:16 (2018)
DOI:10.1038/s41572-018-0014-7

文献

PMID:25964223

著者

Salameh H, Raff E, Erwin A, Seth D, Nischalke HD, Falleti E, Burza MA, Leathert J, Romeo S, Molinaro A, Corradini SG, Toniutto P, Spengler U, Daly A, Day CP, Kuo YF, Singal AK

タイトル

PNPLA3 Gene Polymorphism Is Associated With Predisposition to and Severity of Alcoholic Liver Disease.

雑誌

Am J Gastroenterol 110:846-56 (2015)
DOI:10.1038/ajg.2015.137

文献

PMID:21254164 (PNPLA3)

著者

Stickel F, Buch S, Lau K, Meyer zu Schwabedissen H, Berg T, Ridinger M, Rietschel M, Schafmayer C, Braun F, Hinrichsen H, Gunther R, Arlt A, Seeger M, Muller S, Seitz HK, Soyka M, Lerch M, Lammert F, Sarrazin C, Kubitz R, Haussinger D, Hellerbrand C, Broring D, Schreiber S, Kiefer F, Spanagel R, Mann K, Datz C, Krawczak M, Wodarz N, Volzke H, Hampe J

タイトル

Genetic variation in the PNPLA3 gene is associated with alcoholic liver injury in caucasians.

雑誌

Hepatology 53:86-95 (2011)
DOI:10.1002/hep.24017

文献

PMID:26482880 (PNPLA3, TM6SF2, MBOAT7)

著者

Buch S, Stickel F, Trepo E, Way M, Herrmann A, Nischalke HD, Brosch M, Rosendahl J, Berg T, Ridinger M, Rietschel M, McQuillin A, Frank J, Kiefer F, Schreiber S, Lieb W, Soyka M, Semmo N, Aigner E, Datz C, Schmelz R, Bruckner S, Zeissig S, Stephan AM, Wodarz N, Deviere J, Clumeck N, Sarrazin C, Lammert F, Gustot T, Deltenre P, Volzke H, Lerch MM, Mayerle J, Eyer F, Schafmayer C, Cichon S, Nothen MM, Nothnagel M, Ellinghaus D, Huse K, Franke A, Zopf S, Hellerbrand C, Moreno C, Franchimont D, Morgan MY, Hampe J

タイトル

A genome-wide association study confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis.

雑誌

Nat Genet 47:1443-8 (2015)
DOI:10.1038/ng.3417

LinkDB

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