Lawrence J. Koep

Fifteen Years of Clinical Liver Transplantation

Liver transplantation in humans was first attempted more than 15 yr ago. The 1-yr survival has slowly improved until it has now reached about 50%. In our experience, 46 patients have lived for at least 1 yr, with the longest survival being 9 yr. The high acute mortality in early trials was due in many cases to technical and management errors and to the use of damaged organs. With elimination of such factors, survival increased. Further improvements will depend upon better immunosuppression. Orthotopic liver transplantation (liver replacement) is the preferred operation in most cases, but placement of an extra liver (auxiliary transplantation) may have a role under special circumstances.

Liver transplantation for advanced liver disease with alpha-1-antitrypsin deficiency

ALPHA-1-antitrypsin deficiency associated with chronic obstructive airway disease was recognized in 1963 by Laurell and Ericksson.1 In 1969, Sharp2 described the first cases of alpha-1-antitrypsin-...

Canine and human liver preservation for 6 to 18 hr by cold infusion.

SUMMARY Forty-one dog livers were preserved with cold, lactated Ringers, plasma, or intracellular (Collins) solutions. Consistent survival was obtained with all three solutions for 9 hr. After 18 hr, the plasma and Collins solutions permitted survival, with the Collins solution having a slight overall advantage. The method using Collins solution has been used to preserve seven human livers in Los Angeles, to transport the organs to Denver, and to transport them as orthotopic grafts from 6 hr, 45 min to 10 hr later.

Excisional treatment of cavernous hemangioma of the liver

Fifteen patients had hepatic hemangiomas removed with liver resections that ranged in extent from local excision to right trisegmentectomy. There was no mortality and little morbidity. The propriety and feasibility of extirpative treatment of such liver tumors has been emphasized by this experience.

Acute neurological complications after liver transplantation with particular reference to intraoperative cerebral air embolus.

Nine of 48 adult patients who underwent orthotopic liver transplantation developed significant clinical neurological abnormalities recognized shortly after operation. Decrease in consciousness occurred with resultant coma, focal and generalized seizures and the occasional appearance of a state of akinetic mutism. Neuropathological abnormalities consisted of multifocal areas of infarction in cerebral cortex and basal ganglia in five patients, central pontine myelinolysis in five (often more extensive than usually reported), Wernickes encephalopathy in three, glial nodules in two, and fungal abscesses in one. Alzheimer II astrocytosis was found in all brains available for retrospective study. There was direct evidence in two of the patients that air embolization from the homografts had occurred. Correlation of this with the brain infarcts in these and other cases seems reasonable. The ease with which air passed to the systemic circulation is explicable by the right to left venous-arterial shunts that are common in chronic liver disease. With the delineation of this cause for the neurologic complications, measures to prevent it in future cases have been described.

Thoracic duct fistula and renal transplantation.

Thoracic duct drainage (TDD) was established for 21 – 115 days in 40 kidney recipients with an average removal per patient day of 4.7 I lymph and 1.88 billion cells. Cellular and humoral immunity were depressed. TDD and immunosuppressive drugs were started at transplantation in 35 recipients of cross-match negative grafts. Although the results were better than in precedent non-TDD controls, eight patients rejected their grafts before a full TDD effect, and three of the eight developed predominantly anti-B lymphocyte cytotoxic antibodies which were probably responsible for positive cross-matches with their next donors. With continuing TDD, all eight patients had good initial function after early retransplantation. In five more “nontransplantable” patients with performed cytotoxic antibodies, TDD was started 30–56 days before transplantation. In these five pretreated patients, antibodies persisted with positive antidonor cross-matches. Hyperacute rejection occurred repeatedly in two patients with high anti-T (and anti-B) titers, but was surmounted in three patients with lower titers. From the clinical and immunologic data, we have concluded that TDD should be used for pretreatment of all cases with or without prior antibodies, and have suggested an adjustable management plan that takes into account new developments in antibody monitoring.

Cryopreservation of pig and human liver slices.

The ability to cryopreserve human liver slices would greatly enhance the opportunities to test potentially hepatotoxic drugs and environmental contaminants as well as the metabolism of these compounds. This study focused on trying to cryopreserve pig and human liver slices. Since the acquisition of human liver tissue is unpredictable and scarce, an animal model was sought to predict problems associated with cryopreservation of human tissue. The pig liver was chosen because of its anatomical and physiological resemblance to human liver. The human liver tissues that did become available were obtained through the Arizona Organ Bank and the National Disease Research Interchange and from surgical liver resections. An in vitro culture system that employed precision-cut liver slices was used in this study. Different types and concentrations of cryoprotectants, cooling rates, and culture media were all tried in an attempt to cryopreserve pig and human liver slices. The viabilities of fresh and cryopreserved liver slices were evaluated using slice K+ retention and protein synthesis. Pig liver slices following cryopreservation retained between 80 and 85% of intracellular K+ content and protein synthesis as compared to controls using 1.4 M Me2SO, a 12 degrees C/min cooling rate, and a rapid rewarming rate of direct submersion of the slice into 37 degrees C fetal calf serum. Human liver slices following cryopreservation retained between 54 and 89% of intracellular K+ content and protein synthesis as compared to controls using the same protocol as for pigs, except that lower cooling rates were giving better results. The large variation seen in cryopreserved human liver slices was due to the length of warm and cold ischemia to which the tissue was exposed before arriving at the laboratory. This study indicated that pig and human liver slices can be cryopreserved and used for future toxicological and metabolic studies.

Homotransplantation of the liver in a patient with hepatoma and hereditary tyrosinemia

A girl with hereditary tyrosinemia, diagnosed at 6 months of age, was treated with a diet restricted in phenylalanine and tyrosine. At 9 1/2 years of age she developed an acutely enlarged liver and spleen, and the diagnosis of hepatocarcinoma was made. The patient received a liver transplant and tyrosine metabolites became normal while she was receiving a regular diet. Three months later, an infected thrombosis of the portal vein caused her death. Liver transplant appears to be an effective method of enzyme replacement in tyrosinemia and should be considered for prevention of hepatoma.

Major colonic complications of hepatic transplantation

Patient 1. A 2 89 girl underwent hepatic transplantation for biliary atresia. Despite good hepatic function, a bile leak necessitated biliary revision at two weeks. This was accompanied by a brief period of rectal bleeding, which ceased spontaneously. On her sixty-fifth post-transplant day the patient underwent negative exploratory laparotomy because of suspicion that an abdominal abscess was present. Four days later, massive hematochezia recurred. Laparotomy revealed bleeding from a cecal ulcer, necessitating right hemicolectomy with ileotransverse colostomy. Bleeding ceasd hut pulmonary and hepatic failure rapidly developed. Diffuse cytomegalovirus inclusion disease of the lung, liver, and brain was found. Patient 2. A 16-year-old girl received an orthotopic hepatic transplant for chronic active hepatitis. Despite an initially benign course, rejection occurred on the forty-seventh post-transplant day, necessitating increased steroid administration. Five days later, hepatic function was again normal, but the following day free intraperitoneal air was seen on chest x-ray. Exploration of the abdomen disclosed a freely perforated diverticulum of the right colon with diffuse peritonitis. Hemicolectomy with ileostomy and mucous

The Pretreatment Principle in Renal Transplantation as Illustrated by Thoracic Duct Drainage

In spite of all that has been achieved, renal transplantation still provides a flawed and unpredictable service. In the average American center in the decade of the seventies, less than half the recipients of first cadaver kidneys had graft function by the end of the first postoperative year. One reason may be neglect of what has been called the “forgotten pretreatment principle.” It is that subject which is addressed here, with particular emphasis on thoracic duct drainage (TDD).