HLA class I matching is responsible for the hepatic lesions in recurrent viral hepatitis B after liver transplantation.
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Biomedical subjects
Publications and source records attributed to D Houssin.
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Four cases of tension mucocele of the cystic duct of the graft after orthotopic liver transplantation have been described in the English literature. We report the case of a mucocele of the recipient's cystic duct occurring in a patient who underwent liver transplantation for sclerosing cholangitis secondary to histiocytosis X. At variance with the 4 previously reported cases, this complication could be related to progression of the initial disease in the recipient's cystic duct. To avoid such a biliary complication in patients undergoing a liver transplantation for sclerosing cholangitis, resection of the extra-hepatic duct must be as large as possible and choledochojejunostomy seems to be the best procedure for biliary reconstruction.
Pathology of the inferior vena cava is not frequently encountered in the context of liver transplantation. Such a pathology was observed in 7.9% of our recipients, in the pre- intra- and post-operative period. Pre-existing anomalies of the IVC consisted the absence of the retrohepatic vena cava in 7 children with biliary atresia; technical adjustments were quite simple. During the operative period, dissection of the supra-hepatic vena cava was made very difficult in 2 patients with hepatic alveolar echinococcosis complicated by secondary biliary cirrhosis it was necessary to make a trans-diaphragmatic approach to the inferior vena cava. Post-operative inferior vena cava thrombosis occurred in four recipients, in three cases, it was caused by the inadequate size of the graft and major anastomotic discrepancy between the inferior vena cava of donor and recipient and in one case IVC thrombosis occurred in a context of allergy to heparin. Six of the 13 recipients with pathology of inferior vena cava died directly of indirectly because of these problems. Analysis of the causes of this pathology and their possible correction will perhaps allow better results in these patients who undergo liver transplantation.
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Previous data have shown that lymphocytes from pregnant women, but not from non-pregnant individuals, displayed progesterone receptors. These receptors are inducible in normal human lymphocytes in vitro by mitogenic or allogeneic stimuli. The present study was designed to test the role of in vivo allogeneic stimulation in inducing progesterone receptors in lymphocytes from transplanted and transfused patients. Receptors were detected by immunohistology using a progesterone receptor-specific MoAb and avidin-biotin system. Peripheral blood lymphocytes from 56 healthy pregnant women, 8 liver-transplanted patients and 15 transfused patients contained significantly more receptor-positive cells (P less than 0.001) than those of non-pregnant individuals. In transplanted and transfused patients no correlation was found between the percentage of positive lymphocytes and age, sex or transplant survival. Our results show that in these three groups the percentage of receptor-bearing lymphocytes was higher than in normal subjects.
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Recent improvements in the results of orthotopic liver transplantation (OLT) have made this a well-accepted treatment for patients with severe hepatic failure. Current problems encountered following OLT are discussed. Immediate complications comprise surgical bleeding, primary graft non-function, and graft failure due to hepatic artery occlusion. Secondary complications are frequent. Surgical ones include biliary and vascular (hepatic artery thrombosis most often) problems, as well as intra-abdominal abscesses associated with gastrointestinal perforation, biliary leak, graft ischaemia or an infected haematoma. 40% of patients having undergone OLT will be reoperated on, 2/3 of them within 3 months. Non-surgical complications are mostly pulmonary. The risk of pneumonitis is increased by prolonged mechanical ventilation; it is always potentially disastrous in the immunosuppressed, transplanted patient. Hypertension is also often seen in the early postoperative period; it requires prompt treatment. Early renal impairment after OLT is common, and of better prognosis than late onset renal failure, which is generally associated with shock, graft failure, sepsis or use of nephrotoxic agents. Seizures, usually only one, occur in about 10% of patients; recovery is complete. Encephalopathy with intracranial oedema related to fulminant hepatitis has a worse prognosis, but survival figures are quite encouraging. Three type of rejection are described after OLT: 1) severe accelerated rejection (very rare), 2) acute rejection encountered in about 70% of patients over the first 3 months, and 3) late rejection, which can lead to the vanishing bile duct syndrome (VBDS). Diagnosis of rejection is made by liver biopsy. Prophylactic immunosuppression includes cyclosporin, methylprednisolone and azathioprine. Cyclosporin toxicity and drug interactions are reviewed. Treatment of acute rejection episodes comprises an initial bolus of high doses of corticoid drugs; if there is no response, antilymphocyte globulin or monoclonal antibodies may have to be used. Infection is the main cause of death following OLT. Early infections, mostly intra-abdominal and pulmonary, are bacterial or fungal. Vital (especially CMV) and other opportunistic infections occur generally after the second week. Retransplantation, carried out in 10 to 25% of patients, may be urgent in case of primary graft failure, or hepatic artery thrombosis associated with graft failure, or hepatic artery thrombosis associated with graft failure. Other indications are early graft rejection with severe hepatic dysfunction, chronic rejection with severe VBDS, and recurrence of the initial disease.
In the present study, subtotal hepatectomy was evaluated as a model of acute liver failure in the rat. Sprague-Dawley rats, weighing 250-300 g, underwent hepatectomy under varying basal conditions of temperature and glucose administration. Rats operated and maintained postoperatively at ambient temperature (25 degrees C external environment) developed hypothermia with a rate of return to normal temperature which was related to the extent of hepatectomy and the availability of glucose postoperatively. However, no significant difference in survival was observed between groups maintained at ambient temperature and those whose core temperature was maintained at 37 degrees C by passive external warming. Severe hypoglycemia was observed in rats undergoing 90 and 95% hepatectomy without glucose postoperatively. With 20% glucose available in drinking water the mortality of 90% hepatectomy was reduced from 95 to 40% (p less than 0.0001). With increase of the hepatectomy to 95%, 90% mortality was observed despite glucose support. Transplantation of 4 x 10(7) isolated syngeneic hepatocytes intraperitoneally at the time of hepatectomy did not increase survival after 90 or 95% hepatectomy; addition of testosterone therapy did not improve survival either alone or with hepatocyte transplantation. In this study, hepatectomy exceeding 90% was lethal and did not respond to the supportive measures provided. Hepatocyte transplantation and testosterone pretreatment, both therapies which are thought to increase regeneration, were ineffective in improving survival in this resection model.
Xenotransplantation between different species may possibly solve some of the difficulties associated with human donor organ availability. However, organ xenografts are very rapidly rejected, particularly in discordant donor-recipient combinations, due to the presence of natural cytotoxic antibodies in the recipient. The purpose of this study was to evaluate the efficacy of two potential inhibitors of a xenogeneic antigen-antibody reaction: Iloprost, an analogue of prostacyclin I2, and BN 52063, a PAF-antagonist. Heart (group A) or liver (group B) transplantations were performed in the guinea pig-to-Lewis rat donor-recipient combination. Fifteen minutes prior to revascularization of the graft an intravenous infusion was instituted using saline (0.01 ml/min) (groups A1 and B1), saline and dimethylsulfoxide (DMSO, 0.1 ml/min) (groups A2 and B2), Iloprost (2 ng/Kg/min) (groups A3 and B3) or BN 52063 (6 mg/Kg/min) (groups A4 and B4). Heart graft survival times (min) were 12.3 +/- 1.7 (A1), 13.4 +/- 2.2 (A2), 14.8 +/- 1.0 (A3), 18.3 +/- 1.4 (A4). Liver graft survival times (min) were 158.4 +/- 38.9 (B1), 129.6 +/- 14.4 (B2), 168.1 +/- 18.0 (B3) and 306.2 +/- 36.5 (B4). A significant prolongation (p less than 0.05) was observed in group A4 versus A1, A2, A3 and in group B4 versus B1, B2, B3. These results suggest that prevention of xenograft rejection using PAF-antagonist in association with other methods should be further investigated.
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