Alcoholic hepatitis: pathogenesis and approaches to treatment.
Alcoholic hepatitis is a necrotizing, often inflammatory, process that is an important precursor to the development of cirrhosis. Acetaldehyde, which is derived from alcohol by the action of alcohol dehydrogenase, is apparently the most important factor leading to alcohol-induced liver injury. Other factors of importance in determining the appearance and rate of progression of liver diseases in patients who are chronic alcoholics include sex, nutritional status, and various immunologic reactions. In addition, there is an incompletely understood genetic predisposition to the development of alcoholic hepatitis. Several histologic features found in patients with alcoholic hepatitis have been evaluated in efforts to determine which are of prognostic value. The predominance of the alcohol-induced injury in zone III of the hepatic lobule; deposition of collagen, IgA, and fibronectin in the space of Disse; defenestration of endothelial cells; and transformation of lipocytes and myofibroblasts to fibroblasts have been investigated. Prolongation of the prothrombin time and marked elevation of serum bilirubin levels are indicators of a subgroup of patients with alcoholic hepatitis who have a poor prognosis, especially if there is also evidence of hepatic encephalopathy. Supportive care and abstinence from alcohol are the foundations of therapy. Corticosteroid therapy appears to decrease the number of early deaths in patients with severe alcoholic hepatitis. Other experimental approaches to therapy include the use of propylthiouracil, anabolic-androgenic steroids, and insulin and glucagon.
Maddrey
W C
WC
University of Texas Southwestern Medical Center, Dallas 75235.
D000079:Acetaldehyde / Q000494:pharmacology; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D045930:Anabolic Agents / Q000627:therapeutic use; D005934:Glucagon / Q000627:therapeutic use; D006519:Hepatitis, Alcoholic / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D007328:Insulin / Q000627:therapeutic use; D008099:Liver / Q000473:pathology; D008111:Liver Function Tests; D011441:Propylthiouracil / Q000627:therapeutic use
D000305:Adrenal Cortex Hormones; D045930:Anabolic Agents; D007328:Insulin; D011441:Propylthiouracil; D005934:Glucagon; D000079:Acetaldehyde