Alcoholic liver disease

Lawrence Lumeng, David Crabb

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Important mechanisms responsible for alcohol-induced liver injury include mitochondrial damage and loss of ATP, formation of acetaldehyde- and other aldehyde-protein adducts, release of reactive oxygen species (ROS) from mitochondrial electron transfer chain, CYP2E1, and activated Kupffer cells (KCs); weakening of antioxidant defense systems; and increased intestinal permeability with endotoxemia. Endotoxin interacts with ethanol and/or acetaldehyde, and such interaction leads to a complex cascade of autocrine and paracrine pathways that involve the release of cytokines (proinflammatory, anti-inflammatory, and mutagenic), chemokines, and eicosanoids. These pathways are mediated by activation of KCs, induction of proliferation, and other phenotype changes in hepatic stellate cells (HSCs) leading to transformation to myofibroblasts (the latter is responsible for fibrogenesis, chemotaxis, and contractility, therefore contributing to portal hypertension, angiogenic response, and release of additional cytokines), and stimulation of sinusoidal cells (SECs) to release adhesive molecules and cytokines. Recent data implicate 8 likely role of apoptosis as a mechanism of hepatocyte cell death in alcoholic liver disease.

Original languageEnglish
Pages (from-to)208-218
Number of pages11
JournalCurrent Opinion in Gastroenterology
Volume16
Issue number3
DOIs
StatePublished - 2000

Fingerprint

Alcoholic Liver Diseases
Kupffer Cells
Acetaldehyde
Cytokines
Cytochrome P-450 CYP2E1
Hepatic Stellate Cells
Endotoxemia
Myofibroblasts
Eicosanoids
Portal Hypertension
Chemotaxis
Chemokines
Aldehydes
Endotoxins
Adhesives
Hepatocytes
Permeability
Reactive Oxygen Species
Cell Death
Anti-Inflammatory Agents

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Alcoholic liver disease. / Lumeng, Lawrence; Crabb, David.

In: Current Opinion in Gastroenterology, Vol. 16, No. 3, 2000, p. 208-218.

Research output: Contribution to journalArticle

Lumeng, Lawrence ; Crabb, David. / Alcoholic liver disease. In: Current Opinion in Gastroenterology. 2000 ; Vol. 16, No. 3. pp. 208-218.
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