Biliary lipid composition after liver transplantation: effect of allograft function and cyclosporine.
Biliary lipid composition and bile flow are altered after orthotopic liver transplantation. Cyclosporine may have additional effects on biliary lipid composition and secretion. We studied the effects of liver transplantation, allograft function, and cyclosporine on biliary lipids in humans. Changes in lipid composition and secretion were correlated with serum cyclosporine levels, clinical events, and allograft function. Bile samples were withdrawn via a T-tube at interval time points in 17 patients during the first 3 months posttransplantation. Total and individual bile acid, cholesterol, and phospholipid were determined using high-performance liquid chromatography. Biliary lipid profiles were then correlated with clinical events, serum cyclosporine levels, and other clinical laboratory values. Biliary lipid concentrations decreased in 3 patients during periods of graft dysfunction (acute cellular rejection, drug-induced hepatitis, and inferior vena caval thrombosis) and increased with resolution of the graft injury. Serum cyclosporine levels were positively correlated with total bile acid, cholesterol, and phospholipid concentrations in bile. There was no relationship between the composition of secreted bile acids and serum cyclosporine levels. Bile acid, cholesterol, and phospholipid secretion were not uncoupled in the presence of cyclosporine. We concluded that (1) a decrease in biliary lipid concentrations may be an indicator of worsened graft function in some allografts; (2) biliary lipid concentrations are correlated with increasing cyclosporine levels; and (3) bile acid composition is unchanged, and uncoupling of secretion of other biliary lipids is not observed in the presence of cyclosporine.
Ko
C W
CW
Department of Medicine, VA Puget Sound Health Care System, University of Washington, Seattle, WA, USA.
Kowdley
K V
KV
Haigh
W G
WG
Lee
S P
SP
D000293:Adolescent; D000328:Adult; D000368:Aged; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism; D015415:Biomarkers; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000378:metabolism* / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000627:therapeutic use*; D050356:Lipid Metabolism; D008099:Liver / Q000502:physiology; D016031:Liver Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous
D001647:Bile Acids and Salts; D015415:Biomarkers; D007166:Immunosuppressive Agents; D016572:Cyclosporine