PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Transplantation. Author manuscript; available in PMC 2010 October 28.
Published in final edited form as:
Transplantation. 1977 February; 23(2): 168–171.
PMCID: PMC2965646
NIHMSID: NIHMS240721

ELEVEN AND TWO-THIRDS YEARS SURVIVAL AFTER CANINE ORTHOTOPIC LIVER TRANSPLANTATION1

The first animal to survive chronically after orthotopic liver transplantation was a mongrel dog that received a hepatic homograft on March 23, 1964. The recipient was estimated to be 2 years old. The unrelated mongrel donor was of a different color and appearance. Immunosuppression was with azathioprine which was stopped after 120 days. Treatment was never resumed. The transplanted liver was biopsied on several occasions during the next 5 years and was always thought to be normal (2, 4).

After a brief illness, the dog died on the night of December 8, 1975, at the estimated age of 14 years and after a total survival post-transplantation of 11 years and 8½ months. He had appeared to be well clinically until 1 or 2 days before death.

For most of the post-transplant period, the dog had normal liver function tests (Fig. 1). However, during the last 12 months of life, there was intermittent transaminasemia and elevation of the serum alkaline phosphatase. A few weeks before death, the serum bilirubin was increased to 2.5 mg/100 ml.

FIGURE 1
Serum biochemistries during the 11 years and 8½ months of survival following orthotopic liver transplantation on March 23, 1964. The values recorded during the last 8 months of life represent individual determinations. All other points on the ...

At autopsy, the liver was of normal size. It weighed 2.7% of the body weight, which was 12.5 kg. The liver had a nutmeg appearance and was hard. There were no abnormal venous collaterals suggestive of portal hypertension. The reconstructed vena cava above and below the liver and the portal vein were normal, with barely detectable sites of anastomosis. To arterialize the liver, a segment of donor aorta in continuity with the hepatic artery had been anastomosed to the infrarenal recipient aorta. Although the hepatic artery was grossly normal, the homograft aorta had extensive calcified atherosclerosis.

Biliary reconstruction was with cholecystoduodenostomy after ligation of the distal common duct. The gallbladder, the common duct, and all the intrahepatic ducts were filled with small or medium-sized stones or else with a soft, variably colored green to orange sludge. The stone analysis showed predominantly bilirubin with only trace amounts of cholesterol and bile salts.

Other significant findings at autopsy were pulmonary edema, coronary artery disease, and left ventricular hypertrophy. The immediate cause of death was congestive heart failure.

Histopathological evaluation of the homograft revealed portal fibrosis and linking of the enlarged portal tracts to one another by connective tissue septa (Fig. 2). There was concentric scarring around the interlobular and septal bile ducts and proliferation of ductules at the margins of the portal tracts. Many of the larger bile ducts were dilated and filled with inspissated bile. The epithelium of the affected ducts was ulcerated and there were aggregates of small lymphocytes, plasma cells, and macrophages around the ducts. A few bile “thrombi” were present in the centrilobular part of the bile canaliculi. Liver cell damage was slight. The arteries and arterioles were normal. These changes are typical of chronic large duct biliary obstruction. There was no evidence of rejection.

FIGURE 2
Canine hepatic homograft at autopsy 11 years and 8½ months after transplantation. Fibrous septa link enlarged portal tracts (arrows). There is proliferation of bile ductules and concentric scarring and mononuclear cell infiltration around the ...

The thymus, mesenteric and mediastinal lymph nodes, and Peyer’s patches appeared to be normal. The spleen had been removed at the time of transplantation.

Examination of the rest of the tissues confirmed the narrowing of the coronary arteries by atherosclerosis, the hypertrophied left ventricle, and the congestion and edema of the lungs. The atherosclerosis in the homograft aorta was severe, with large patches of calcification and bone formation with marrow. By contrast the recipient aorta was normal. The kidneys were normal.

Thus, although the dog died primarily of cardiovascular manifestations of old age, a potentially lethal biliary duct complication was present which would have independently caused death within a short time. A partial obstruction of the cystic duct was apparently the main cause of the extensive stone and sludge formation that had affected both the extrahepatic and intrahepatic ducts. The intrahepatic biliary plugging with inspissated bile casts was similar to a syndrome that we (1, 3) and Waldram et al. (5) have noted in humans. Such findings in animals and man point again to the reconstructed biliary duct system as the Achilles’ heel of liver transplantation.

The completely normal findings in this dog’s lymphoid system were of interest, since no immunosuppression whatever had been given for 11½ years.

Footnotes

1This work was supported by Research Projects MRIS 8118-01 and 7227-01 from the Veterans Administration and by Grants AM-17260 and AM-0772 from the National Institutes of Health.

LITERATURE CITED

1. Martineau B, Porter KA, Corman J, et al. Surgery. 1972;72:604. [PMC free article] [PubMed]
2. Starzl TE, Marchioro TL, Porter KA, et al. Surgery. 1965;58:131. [PMC free article] [PubMed]
3. Starzl TE, Porter KA, Putnam CW, et al. Surgery. (in press)
4. Starzl TE, Putnam CW. Experience in hepatic transplantation. Philadelphia: W B Saunders Co; 1969.
5. Waldram R, Williams R, Calne RY. Transplantation. 1975;19:382. [PubMed]