Alcoholic hepatitis pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Assosciate Editor(s)-In-Chief: Prashanth Saddala M.B.B.S
Overview
Pathophysiology
- The amount and duration of alcohol (EtOH) necessary to damage the liver is variable and relates to host factors.
- Most patients with established liver disease continuously consume 60-80 g/day of ETOH (about 8 beers, one liter of wine, or half a pint of liquor) for 10 to 20 years. After 20 years of such behavior, most will have fatty changes, but only half will have cirrhosis.
- Diffuse focal liver cell necrosis with polymorphonuclear, mononuclear, fatty infiltration. Neutrophilic infiltration in particular is unusual for other forms of hepatitis.
- Mallory bodies
- Perinuclear eosinophilic inclusions from intermediate filaments found in alcohol liver disease that can also be seen in fatty liver, primary biliary cirrhosis, hepatitis C, obesity.
- Perivenular inflammation
- “Ballooning” of hepatocytes results from the accumulation of fat and water.
- Swollen hepatocytes and collagen deposition leads to increased sinusoidal pressures, and perhaps portal hypertension.
- Perisinusoidal fat cells transform into fibroblasts.
- Other non-essential changes that might be present include bridging necrosis, bile duct proliferation, and cholestasis.
Molecular Biology
Potential mechanisms of alcohol associated liver disease include:
- ETOH generates excess NADH, which slows gluconeogenesis, increasing lactate production, and leading to fatty acid accumulation.
- Acetaldehyde is a toxic metabolite that can impair hepatocyte function
- Alcohol metabolism consumes oxygen and contributes to centrilobular hypoxia
- Neutrophil infiltration – perhaps in association with reactive oxygen species
- Other minor pathways of alcohol metabolism are upregulated in alcoholics, which may produce more dangerous oxygen intermediates. A microsomal pathway has been called the microsomal enzyme oxidation system (MEOS). Polymorphisms of enzymes in this system (P4502E1 in particular) may contribute to the predisposition of some individuals to alcohol associated liver damage. P4502E1 also appears to increase acetominophen metabolism to toxic metabolites, and may play a role in acetominophen associated liver disease in patients who drink alcohol.
- Inflammation and collagen deposition in the perivenular (zone 3) region of the hepatic sinusoids and the space of Disse, impede flow, increasing pressure. Perivenular cell necrosis may be found.