TY - JOUR
T1 - Bile acids in xenogeneic ex-vivo liver perfusion
T2 - Function of xenoperfused livers and compatibility with human bile salts and porcine livers
AU - Foley, David P.
AU - Collins, Bradley R.
AU - Magee, John C.
AU - Platt, Jeffrey L.
AU - Katz, Elizer
AU - Harland, Robert C.
AU - Meyers, William C.
AU - Chari, Ravi S.
PY - 2000/1/27
Y1 - 2000/1/27
N2 - Background. In recent years, hepatic support systems using xenogeneic cells have been developed to support patients in fulminant hepatic failure. The extent to which xenogeneic hepatocytes metabolize and excrete human organic anions is unclear. In these studies we examined the ability of the ex vivo porcine liver to clear human bile acids during extracorporeal liver perfusion (ELP). Methods. Four patients with fulminant hepatic failure underwent extracorporeal liver perfusion with 9 porcine livers. The venovenous circuit was designed as previously described (NEJM, 1994,331:234) as were the immunologic features (Transplantation 1994,58:1162). Bile from the porcine liver and serum samples were collected hourly during perfusion. Three bile acids (glycocholic, glycodeoxycholic, taurodeoxycholic acid) were selected as markers for human bile and three (glycohyocholic, glycohyodeoxycholic, and glyco-3α-hydroxy-6-oxo-5β-cholanoic acid) for markers of pig bile. Bile acids from both serum and bile were processed and analyzed through high performance liquid chromatography. The Students' t test was used for statistical analysis. Results. The mean duration of perfusions was 4.1±1.5 hr. The mean total bile acid clearance from serum (243±44 μmol/h) was similar to the total bile acid biliary excretion (286±84 μmol/hr, P=0.06). After 1 hr of perfusion, bile samples demonstrated a predominance of pig bile salts (65%). After 3 hr of perfusion, human bile acids made up 85% of total biliary bile acids. Pig bile acids appeared in patients' sera after 1 hr of perfusion, and after 3 hr, 35% of serum bile salts were pig-specific. Conclusions. Porcine livers perfused with human blood can clear the serum of potentially toxic human bile acids and excrete them into bile. Simultaneously, the percentage of pig-specific bile acids in patient serum increases during xenogeneic perfusion for unknown reasons. The relative hepatic uptake of bile acid from serum is similar to bile acid excretion in bile. Further development of systems using porcine livers or hepatocytes is warranted.
AB - Background. In recent years, hepatic support systems using xenogeneic cells have been developed to support patients in fulminant hepatic failure. The extent to which xenogeneic hepatocytes metabolize and excrete human organic anions is unclear. In these studies we examined the ability of the ex vivo porcine liver to clear human bile acids during extracorporeal liver perfusion (ELP). Methods. Four patients with fulminant hepatic failure underwent extracorporeal liver perfusion with 9 porcine livers. The venovenous circuit was designed as previously described (NEJM, 1994,331:234) as were the immunologic features (Transplantation 1994,58:1162). Bile from the porcine liver and serum samples were collected hourly during perfusion. Three bile acids (glycocholic, glycodeoxycholic, taurodeoxycholic acid) were selected as markers for human bile and three (glycohyocholic, glycohyodeoxycholic, and glyco-3α-hydroxy-6-oxo-5β-cholanoic acid) for markers of pig bile. Bile acids from both serum and bile were processed and analyzed through high performance liquid chromatography. The Students' t test was used for statistical analysis. Results. The mean duration of perfusions was 4.1±1.5 hr. The mean total bile acid clearance from serum (243±44 μmol/h) was similar to the total bile acid biliary excretion (286±84 μmol/hr, P=0.06). After 1 hr of perfusion, bile samples demonstrated a predominance of pig bile salts (65%). After 3 hr of perfusion, human bile acids made up 85% of total biliary bile acids. Pig bile acids appeared in patients' sera after 1 hr of perfusion, and after 3 hr, 35% of serum bile salts were pig-specific. Conclusions. Porcine livers perfused with human blood can clear the serum of potentially toxic human bile acids and excrete them into bile. Simultaneously, the percentage of pig-specific bile acids in patient serum increases during xenogeneic perfusion for unknown reasons. The relative hepatic uptake of bile acid from serum is similar to bile acid excretion in bile. Further development of systems using porcine livers or hepatocytes is warranted.
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U2 - 10.1097/00007890-200001270-00009
DO - 10.1097/00007890-200001270-00009
M3 - Article
C2 - 10670634
AN - SCOPUS:0034719369
SN - 0041-1337
VL - 69
SP - 242
EP - 248
JO - Transplantation
JF - Transplantation
IS - 2
ER -