Two patients with homozygous familial hypercholesterolemia, refractory to medical therapy, underwent complete bile diversion by common-duct ligation and Cholecystotomy, in an attempt to arrest the progression of their xanthomatosis and atherosclerosis by depletion of body cholesterol. Clofibrate was given after operation to one patient, and cholic acid to both, in an effort to enhance further the negative sterol balance. Bile diversion produced an increase of six to eight times in gastrointestinal sterol output, which was not increased further by either clofibrate or cholic acid therapy. Despite a calculated sterol loss of 560 g over 14 months in one patient and 400 g over 10 months in the other, neither plasma cholesterol nor xanthoma size decreased. Continuity of the biliary tree was therefore restored. The data suggest that patients with homozygous familial hypercholesterolemia respond to even massive gastrointestinal sterol depletion with equal increases in sterol synthesis. (N Engl J Med 296:465–470, 1977) Patients with homozygous familial hypercholesterolemia die in adolescence or early adulthood from sequelae of rapidly progressive atherosclerosis.1 Measures used to treat this disorder have not as yet proved successful in altering its natural history even though similar interventions have produced promising results when applied to patients with heterozygous familial hypercholesterolemia, who have lower plasma cholesterol levels and a longer life-span. Because bile acids are closely linked both with cholesterol absorption and with its metabolism, treatment of familial hypercholesterolemia has been directed toward interfering with normal bile acid metabolism.2 Interruption of the normal enterohepatic circulation of bile acids by decreasing their.
ASJC Scopus subject areas