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To study the immunological and metabolic effects of auxiliary liver transplantation (ALT), a simple ALT model in rats was developed using the cuff application. Effects of transient parking of normal liver were tested in congenitally hyperbilirubinemic Gunn rats. Serum bilirubin concentrations in Gunn rats, transplanted heterotopically with normal livers of Wistar rats, were dramatically reduced and maintained within normal levels. The graftectomy was performed safely 1 month after transplantation, but total bilirubin levels did not return to the preoperative value of the Gunn rats. It is possible that hepatic stem cells included in ALT liver migrated to the host liver and differentiated into cells capable of producing certain enzymes.

The Gunn rat is an excellent model of Crigler-Najjar syndrome, type 1. In previous studies we demonstrated that heterotopic 15-20-cm jejunal transplants from Wistar rats lowered serum bilirubin levels by 40%, and the reduction was transient (6 weeks). In contrast, orthotopic transplants decreased bilirubin levels by 60% and the effect persisted throughout the 8-week study. This study was initiated to identify the luminal substance(s) which are responsible for the persistent bilirubin-lowering effect of jejunal transplants. Thirty-one Wistar to Gunn 15-20-cm jejunal transplants were randomized to receive daily Thiry-Vella graft irrigation with 5 ml of normal saline (n = 8); bile salts (cholate + deoxycholate, 40 mg/ml, n = 5; fats (Microlipid, 20 mg/ml, n = 5); proteins (Casec caseinate, 40 mg/ml, n = 5); and sugars (Moducal + Polycose, 40 mg/ml, n = 8). Bilirubin levels were measured spectrophotometrically at weekly intervals. At 4 and 8 weeks, enzyme-induced bilirubin conjugation activity was measured using added known amounts of added bilirubin. Irrigation of the transplants with saline, protein, and sugar resulted in moderate (40%) lowering of serum total and indirect bilirubin levels. Fat was significantly more effective, lowering mean total bilirubin levels from 9.6 +/- 0.4 to 1.6 +/- 0.2 mg/dl at 6 weeks. After this time, bilirubin levels increased slightly. Bile salts were slightly less effective, lowering bilirubin levels at 6 weeks by only 75%. However, this effect persisted and at 8 weeks levels averaged 2.4 +/- 0.2 mg/dl. Conjugating enzyme activity in the transplants increased from 1.4 +/- 0.3 to 2.5 +/- 0.5 mg bilirubin conjugated/mg tissue/hr. Luminal fats and bile salts appear to augment enzyme-induced bilirubin conjugation in heterotopic jejunal transplant recipients.

A neurologically normal 3-year-old girl with Type I Crigler-Najjar syndrome was successfully treated with orthotopic liver transplantation. Preoperative serum bilirubin concentrations as high as 31 mg per dl were not diminished with phenobarbital or phototherapy. Bilirubin fractionation of duodenal bile prior to transplantation revealed 87.1% unconjugated bilirubin and 12.9% monoconjugates as determined by alkaline methanolysis-high-performance liquid chromatography. Postoperatively, the serum bilirubin concentration quickly fell to normal. Uridine diphosphate glucuronyl transferase activity in the recipient liver was not detectable. The gallbladder bile bilirubin concentration of 23.9 mg per dl was less than 15% of previously reported normal values. Since devastating kernicteric brain injury is the invariable outcome of Type I Crigler-Najjar syndrome, liver transplantation should be performed when phototherapy cannot maintain the serum bilirubin concentration at an unequivocally safe level.

A sustained decrease of plasma bilirubin concentrations occurred in homozygous recessive Gunn rats lacking the enzyme uridine diphosphate glucuronyltransferase following infusion into the portal vein of hepatocytes from heterozygous nonjaundiced Gunn rats possessing the enzyme. Transplantation of cells capable of continuous enzyme production could be an effective mode of therapy for congenital enzyme deficiency diseases.