Homotransplantation of the liver

Abstract

The feasibility of hepatic homotransplantation has been clearly established in principle inasmuch as several animals are still alive almost 3 years after complete hepatectomy and liver replacement. Both orthotopic and auxiliary operations are complicated surgical techniques. Nevertheless, the results in dogs are comparable to those which can be obtained with homotransplantation of the kidney.

In man the problem is more difficult. In patients who have a need for such operations, there is invariably a metabolic disorder more complex than that caused by renal failure. In addition, the new organ must function efficiently from the beginning since its complete functional failure leads to death within a few hours. There is no recourse to an artificial liver to maintain life until the reversal of an injury which is caused by either ischemia or rejection.

Nevertheless, research of several kinds may soon make possible the successful use of hepatic transplantation procedures for the definitive treatment of human liver disease as exemplified by the reports in this symposium concerning new techniques of organ preservation, histocompatibility analysis, and immunosuppression.

Figure 1

Method of further cooling a liver homograft just before its removal. Donor animals are operated on with total body hypothermia of 29–31°C. Cold lactated Ringer’s solution is infused through the portal vein at the same time the donor animal is exsanguinated. (By permission of Surgery, Gynecology and Obstetrics, 1960, 111: 733.)

Figure 2

Reconstruction after orthotopic liver homotransplantation. Internal biliary drainage is with a cholecystoduodenostomy. In this preparation the aorta has been transplanted in continuity with the hepatic artery of the homograft. Alternatively, the homograft hepatic artery may be connected to the recipient hepatic or right renal artery. (By permission of Surgery, 1965, 58: 131.)

Figure 3

Method for decompression of inferior vena caval and splanchnic systems during removal of recipient liver and replacement with a homograft. Note that a preliminary portacaval shunt has been placed. By means of this temporary anastomosis, the two venous systems are connected, allowing their decompression with a single external bypass. (By permission of Surgery, Gynecology and Obstetrics, 1960, 111: 733.)

Figure 4

Course of an animal which never had any clinically evident homograft rejection. Note rapid weight gain following cessation of therapy at 4 months. The pronounced leukocytosis after withdrawal of immunosuppression was commonly seen. This animal is still alive after 2 years and 10 months, having received no immunosuppressive therapy for 2¹/₂ years of this time.

Figure 5

Two biopsies from a hepatic homograft. The first (A) was taken after the host had been receiving azathioprine for 121 days. The lobular architecture is distorted by thick bands of connective tissue which link portal tracts to each other and to central veins. Hepatocytes in the pseudolobules of regenerating liver contain much lipid. Azathioprine therapy was then discontinued, and 77 days later, 198 clays after transplantation, the second biopsy (B) was taken. There has been a striking improvement in the general liver architecture. Connective tissue bands are no longer so obvious and the liver cells look more healthy. This animal is still alive 2¹/₂ years after operation. (By permission of Surgery, 1965,58: 131.)

Figure 6

Case 2 of Colorado series: treated human orthotopic hepatic homograft at 22 days. A, B, and C show typical appearance of the tissue. A, centers of lobules appear dark because the hepatocytes contain excess lipofusein. Increase of portal connective tissue was probably present before homotransplantation. There is patchy cellular infiltration, particularly in smaller portal tracts. Hematoxylineosin; ×20. B, lobular architecture is essentially normal. Reticulin stain; ×20. C, portal tract is infiltrated by mononuclear cells. There is proliferation of small bile ducts. Hematoxylineosin; ×250.

Figure 7

Auxiliary liver transplantation. A, method of Welch. Note that portal venous inflow is from the inferior vena cava. The homograft undergoes rapid atrophy. B, modification of Welch method in which nonhepatic splanchnic flow is diverted through the homograft. With this preparation, the homograft retains its size and the animal’s own liver shrinks. It is usually more convenient to bring the hepatic artery behind rather than in front of the portal vein as depicted. (By permission of Surgery, Gynecology and Obstetrics, 1965, 17: 121.)

Figure 8

Method of auxiliary liver transplantation which has received a clinical trial. The procedure has been used twice at the University of Colorado Medical Center in patients with terminal Laennec’s cirrhosis. A, B, first-stage portacaval anastomosis is performed. This will usually be necessary for control of variceal hemorrhage. C, revascularization of the auxiliary liver in the right paravertebral gutter. (By permission of Pediatric Clinics of North America, 1966, 13: 381.)