JVD 11/02
UPDATE ON ETOH HEPATITIS
CURRENT EPIDEMIOLOGY
• ETOH liver disease affects about 2 million people in the US, 50% of heavy drinkers who are
hospitalized display some evidence of ETOH hepatitis, 25,000 deaths/year.
• ETOH liver disease develops after “threshold” dose of ethanol has been consumed: 600 kg per
men, 150-300 kg per women. This is equivalent to 8 12-oz beers, 1L wine, or 0.5 pint of distilled
spirit daily for 20 years.
• Mortality from ETOH hepatitis is determined by severity of disease: mild disease (bili <5.0 mg/dl)
carries a 100% disease survival at one month, 78% survival in 3 years; while severe disease ( DF
>32 using formula 4.6 (PT-control) + Tbili) carries a 50 % one month mortality. Hepatic
encephalopathy can also be used as a marker for severity, and carries a poor prognosis.
• Cofactors associated with the development of alcoholic liver disease: not all alcoholics get liver
disease.
o Hereditary variations: under investigation of HLA subtypes, ADH polymorphisms.
o Gender: females are not only more susceptible to liver disease at lower doses, but also
tend to progress even during abstinence, likely due to decreased levels of gastric ADH
and impaired upregulation of fatty acid metabolism.
o Etoh liver injury correlates strongly and inversely with nutritional status, likely due to
inadequate intake of antioxidant vitamins and excess intake of polyunsaturated fats.
o Viral liver disease: additive risk for developing liver disease.
FASCINATING PATHOPHYSIOLOGY AND PATHOLOGY
• Ethanol is oxidized by ADH to acetaldehyde which is then oxidized by ALDH to acetate, these are
cytoplasmic enzymes. When overwhelmed, the MEOS (microsomal ethanol oxidizing system)
and catalase (perixomes and mitochondrial enzyme) are responsible for oxidation. While ADH
uses reduces NAD+ to NADH, MEOS enzymes oxidizes NADPH to NADP+, thus producing
oxygen radicals. Gastric ADH plays a role in first pass metabolism.
•
Redox alteration: NADH excess provoke steotosis