John J. Fung

Alcoholic liver disease and transplantation.

ALCOHOL has been and continues to be one of the most commonly abused substances in society. One of 10 persons and 1 of 3 families is the victim of alcoholrelated disorders. In the United States it is the fourth most common cause of death in the 35 to 55 year age group. In Europe, 10% of all deaths are secondary to alcohol-related liver disease. Alcohol is oxidized by alcohol dehydrogenase to acetaldehyde. Acetate enters the citric acid cycle and is utilized to make fatty acids, which may cause ballooning of hepatocytes, eventually resulting in degeneration, fatty changes, inflammatory infiltrates, fibrosis, and Mallory’s hyalinization. When they consume the same amount of alcohol, women are at higher risk for disease than men, probably due to their decreased gastric alcohol dehydrogenase activity. In addition, the presence of hepatitis C viral infection, use of acetaminophen, and obesity are identifiable corisk factors for the progression of liver disease. More than 80 g of alcohol per day (ie, 6 to 8 drinks) for more than 8 years can be expected to lead to alcoholic liver disease.

Early experience with FK 506 in liver transplantation

Since the introduction of cyclosporine-steroid therapy in 1980 for liver transplantation, 1 year clinical survival rates have approached 70% for most of the common indications for liver replacement and 5 year survival rates are better than 60%. Nevertheless, allograft rejection continues to be a significant cause of retransplantation or death. Clinical rejection occurs in 70% of liver allograft recipients on cyclosporine-steroid therapy. Many patients require treatment with polyclonal or monoclonal antibody preparations to control acute cellular rejection. An increased risk of opportunistic infection, especially from cytomegalovirus, is associated with such therapy.