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Patients with an augmented or diverted urinary system are considered higher risk recipients in view of increased technical problems and infective complications. We studied the long-term renal graft function and survival in patients with a pretransplant ileal conduit or ileal/caecocystoplasty. Between 1986 and 1997, 14 of 1253 (1.1%) renal transplant recipients had their transplant ureters anastomosed into an abnormal urinary tract. These consisted of ten ileal conduits and four ileal/caecocystoplasties. Median follow up was 42 months (range 1-156). All ten ileal conduits were discharged with a functioning graft. There was one graft loss chronic rejection and one cardiac death. The median creatinine level was 130 mmol/l and 50% have a urinary infection. All the patients with an ileal/caecocystoplasty were discharged with a functioning graft and these are still functioning; median creatinine of 132 mmol/l and 75% have a urinary infection. One- and 3-year graft survival was 93% and 86%. We conclude that the long-term outcome of renal transplantation in carefully assessed patients with an abnormal urinary tract is satisfactory despite a high incidence of urinary infection.

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Choledochocholedochostomy (CCD) with a 7 fr/8 fr Cotton Leung internal biliary stent removed at endoscopic retrograde cholangiography (ERC) 3 months following orthotopic liver transplantation (OLT) was the technique used on our unit for biliary reconstruction. From June 1995 to July 1996, we randomised 37 OLT patients with CCDs to receive either an internal stent (group I, nd = 18) or no stent (group II, n = 19). Patients in group I had an ERC at 3 months for stent removal whereas patients in group II had an ERC if indicated. The mean follow up was 19 (13-26) months. Biliary complications occurred in 9 out of 18 patients in group 1 compared to 1 out of 19 patients in group II (P = 0.007). In group I, ERC was required for complications in 8 patients and early surgery in 2, compared to 1 ERC for abnormal liver function tests in group II. Five of the early complications in group I were stent related. Late biliary stenosis occurred in 1 patient at 9 months. There was one stent-related death. The use of stents contributes to biliary complications and CCD without stenting is safe after OLT.

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University of Wisconsin solution (UW) is now used widely for the preservation of livers for transplantation. However, the use of commercial solutions has added considerably to the cost. We were able to produce a local version of organ perfusion fluid (NOPF) incorporating all the constituents of UW except for the hydroxyethyl starch and adenosine. We compared graft outcome using NOPF with imported grafts perfused with commercial UW solution. The two recipient groups (15 patients each) were similar with respect to age and sex distribution, urgency of transplantation, regraft status and patient and graft survival. Postoperative duration of ventilation, dialysis requirements, peak bilirubin, peak ALT and lowest unsupported prothrombin time were also similar in both groups. In conclusion, local perfusion fluids based on UW can be produced without detriment to graft outcome with considerable financial savings. At our institution, this represents a reduction of 33% in the cost of perfusion fluids.

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Latent or sub-clinical hepatic encephalopathy is a recognized complication of cirrhosis and is thought to represent one end of the spectrum of neuropsychiatric impairment, which occurrs as a result of portal-systemic shunting. We studied the psychometric, analyzed electroencephalography (EEG), and venous blood ammonia responses to an oral glutamine challenge in 17 patients with cirrhosis and in 4 normal controls. The cirrhotics were attending for liver transplant assessment and had no clinical evidence of hepatic encephalopathy. The oral glutamine challenge was repeated following liver transplantation. Five of sixteen patients (31%) showed impaired performance on at least one of the baseline psychometric tests. There was a correlation between fasting venous ammonia and choice reaction time (r = .7, P < .01). Following glutamine challenge there was a significant increase in blood ammonia from a mean fasting value ranging between 58 micromol/L to 120 micromol/L (P < .01), between significant prolongation of reaction times of 387 ms to 428 ms (P < .01), and an increase in mean EEG amplitude between 68.5 microV to 78.6 microV (P < .001). Four normal controls who were challenged with glutamine and 6 cirrhotic patients who were challenged with water showed no change in any of these parameters. Following orthotopic liver transplantation (OLT) the eight patients studied had normal baseline psychomotor performance with significant improvements in digit symbol, digit span, information processing, number connection tests (P < .05), and reaction time (P < .005). Posttransplantation, there were no significant changes in blood ammonia, analyzed EEG, or choice reaction time in response to oral glutamine challenge (six patients). We conclude that short lived changes in blood ammonia (in cirrhotics) can cause significant impairment of sensitive tests of brain function and that psychometric performance is improved following OLT.

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BACKGROUND & AIMS: Intrahepatic bile ducts express a range of lymphocyte adhesion molecules during episodes of inflammation. This may contribute to the susceptibility of biliary epithelium to immunologic damage during liver allograft rejection, graft-versus-host disease, and primary biliary cirrhosis. However, no previous study has shown that these adhesion molecules are functional. The aim of this study was to define the molecular basis of lymphoepithelial interactions within the intrahepatic bile ducts. METHODS: Human intrahepatic biliary epithelial cells (HIBECs) were cultured, and their interaction with resting and activated lymphocytes was studied using a flow-cytometric assay that allowed characterization of the adherent cells and functional investigation of individual adhesive interactions. The capacity of adherent cytotoxic lymphoid cells to damage HIBEC was studied using a standard 51Cr release assay. RESULTS: Allogeneic lymphocytes were bound by HIBECs; this adherence was increased by activation of either participating cell type. Cells with cytotoxic capacity were bound preferentially. At least 50% of the overall adhesion was dependent on lymphocyte function-associated antigen 1. Cytotoxicity assays showed that HIBECs were susceptible to lysis by lymphokine-activated natural killer cells. CONCLUSIONS: This study shows that the adhesion molecules expressed by HIBECs are functional and necessary for the activity of cytotoxic effector lymphocytes.

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The intrahepatic biliary epithelium is susceptible to extensive T-cell-mediated damage during primary biliary cirrhosis, primary sclerosing cholangitis, and hepatic allograft rejection. During these processes, human intrahepatic biliary epithelial cells (HIBEC) become activated and express high levels of the lymphocyte adhesion molecules, intercellular adhesion molecule-1 (ICAM-1) and lymphocyte-associated antigen (LFA)-3, and of class II MHC antigens. It follows that activated HIBEC may also play a direct role in the activation of antigen-specific CD4+ T lymphocytes. The capacity of class II MHC antigen-expressing HIBEC to present antigen and induce specific proliferation of CD4+ T cells was examined in this study. Lines of purified HIBEC were activated by culture with the proinflammatory cytokines interferon gamma (IFN-gamma) and tumor necrosis factor a and were mixed in coculture with allogeneic CD4+ T cells. The result of interaction between these cells was assessed by measurement of lymphoproliferation and IL-2 production. Class II MHC antigen-expressing HIBEC failed to induce either lymphoproliferation or IL-2 production. However, both of these parameters of T-cell activation were positive in cocultures when a costimulation signal was delivered to T cells by adding bivalent anti-CD28 antibodies. The antigen-specific activation of these T cells was further enhanced by the addition of a cross-linking secondary antibody that caused CD28 receptor aggregation. The failure of cytokine-stimulated HIBEC to induce T-cell activation is consistent with the observation that HIBEC do not express the costimulatory CD28 ligands B7-1 or B7-2 at either mRNA or protein levels. It may be concluded that HIBEC are unlikely to play a direct role in activation of antigen-specific CD4+ T lymphocytes within the inflamed liver.

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We report a case of combined coronary artery by-pass grafting and orthotopic liver transplantation on cardiopulmonary bypass, in a 56-yr-old man with rapidly progressive ischaemic heart disease and end-stage liver disease. Three months after surgery he is asymptomatic with normal liver function.

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Intrahepatic biliary epithelial cells were immunomagnetically purified from specimens of disaggregated human liver and were propagated in vitro. After three passes in culture, the cells were shown to be over 85% pure with contaminating leukocytes and endothelial cells constituting less than 2% of the population. Sensitive flow microfluorimetric analysis was performed after immunofluorescence labeling to quantify expression of both class 1 and class II major histocompatibility (MHC) antigens and the adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and lymphocyte function-associated antigen-3 (LFA-3). It was shown that resting human intrahepatic biliary epithelial cells (HIBEC) expressed class 1 MHC antigens, ICAM-1, and relatively low levels of LFA-3. Stimulation with tumour necrosis factor-alpha (TNF-alpha) upregulated expression of ICAM-1, whereas Interferon-gamma (IFN-gamma) and a combination of IFN-gamma and TNF-alpha upregulated class I MHC antigens and ICAM-1 and induced class II MHC molecules. The level of expression of MHC antigens and of ICAM-1 and LFA-3 after stimulation of HIBEC with combined IFN-gamma and TNF-alpha was comparable with the expression of these antigens by an Epstein-Barr virus-transformed B-cell line. The phenotypic similarity between cytokine-stimulated HIBEC and a known antigen presenting cell is consistent with a potential role for biliary epithelial cells in antigen presentation.

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The perfusion of kidneys with anti-CD45 monoclonal antibodies prior to transplantation offers a means of targeting passenger antigen-presenting cells with the aim of reducing the subsequent incidence of rejection episodes. A safety study was performed in humans of such pretreatment in 40 unsensitized recipients of first cadaveric renal grafts, who were followed for 3 months after transplantation. A 50-ml solution containing 2 mg of each of the rat anti-CD45 mAbs YTH 24.5 and YTH 54.12 was injected into the allograft renal artery ex vivo and just before transplantation while the renal vein was kept clamped. No patients died, but 4 grafts were lost. Two were lost due to primary nonfunction, 1 was lost because of late renal artery thrombosis, and 1 was lost to rejection. There were no cases of renal vein thrombosis and 1 trivial renal artery stenosis, and only 2 patients produced human anti-rat antibodies. Between 63.5% and 100% (median 96.4%) of CD45+ cells in the postperfusion biopsies were coated with anti-CD45 as determined by double-immunolabeling. The number of patients experiencing rejection episodes was inversely associated with this "antibody uptake": 75% of the low uptake group (< 95%) had at least 1 rejection episode, compared with 22% of the high uptake group (> or = 95%) (P = 0.001). The complement components C3 and C5b-9 colocalized with perfused anti-CD45 in 32/33 (97.0%) and 11/33 (33.3%) of the biopsy specimens, respectively. We conclude that: (1) this technique appears free of adverse effects, (2) high antibody uptake within the kidney is associated with a lower incidence of rejection, and (3) the antibodies used fix and activate complement in vivo.

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The role of the cytotoxic crossmatch in liver transplantation is generally considered controversial. The development of the flow cytometric crossmatch has allowed the detection of lower levels of donor-directed IgG than is possible with the conventional crossmatch. This assay has been shown to be useful in renal transplantation. However, with the controversial role of the standard cytotoxic crossmatch, the flow cytometric crossmatch has not been used in liver transplantation. Twenty-seven human orthotopic liver allograft recipients were tested for donor-directed IgG using the flow cytometric crossmatch. Thirteen recipients were identified with either T or B lymphocyte-directed IgG. This group had a significantly increased incidence of clinical rejection (75%) as compared with the negative group (29%, P = 0.02, Fisher's exact test). The differences were greatest with B lymphocyte-directed IgG and the rejections were generally steroid sensitive. In this series, the flow cytometric crossmatch proved to be a better prognostic indicator of rejection than the conventional cytotoxic crossmatch. In addition, the association of a positive flow cytometric crossmatch with rejection indicates that the liver follows the same pattern seen in renal and cardiac grafts.

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We report details of two liver transplant procedures in which post-reperfusion coagulopathy was reversed by administration of protamine sulphate. Both procedures were uncomplicated until about 30 min after reperfusion of the graft, when the cut surfaces began to ooze blood. Failure of coagulation was confirmed by thrombelastography and in both cases routine coagulation tests revealed a prolonged kaolin cephalin clotting time (KCT). A heparin-like effect was suspected. Protamine sulphate 50 mg was given i.v., resulting in cessation of bleeding and normalization of the thrombelastogram and KCT.

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10 highly and persistently sensitised patients awaiting renal transplantation underwent extracorporeal immunoadsorption to remove anti-HLA antibodies. 7 patients have since received transplants. Only 1 allograft has been lost because of rejection, and there have been no serious side-effects attributable to treatment. Extracorporeal immunoadsorption may therefore be of considerable value in the management of highly sensitised patients.

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Thirty-three patients with acute liver failure underwent orthotopic liver transplantation, including 16 with fulminant hepatic failure, 15 with late-onset hepatic failure and two with severe acute liver failure (coagulopathy without encephalopathy). Twenty-three (70 per cent) survived to leave hospital and 21 of these are currently alive and well. Outcome correlated with the serum bilirubin level before transplantation (p less than 0.05) but no correlation was found with the variant of acute liver failure, grade of encephalopathy, cerebral oedema, serum creatinine, white cell count, prothrombin time or platelet count at the time of transplantation. Severe coagulation factor deficiencies did not constitute a clinical problem. One patient developed a neurological deficit secondary to cerebral oedema, but otherwise the morbidity reflected that observed in the general population after transplantation. Careful monitoring of intracranial pressure and surveillance (with early aggressive therapy) for bacterial and fungal infections is very important in achieving a successful outcome after transplantation.

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