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A G Sheil

Publications and source records attributed to A G Sheil.

At least 73 records · Page 4Linked to original sources
PubMed1996

Biliary strictures after liver transplantation: clinical picture, correlates and outcomes.

We retrospectively examined 154 adults to ascertain the frequency, site of and pre-disposing factors for biliary strictures after liver transplantation, as well as their management and clinical outcome. Twenty patients (12.5%) were identified with biliary strictures; 16 were non-anastomotic and four were anastomotic strictures. The median time from transplantation to stricture diagnosis was 17 weeks (range 3-366). Of the 16 non-anastomotic strictures, six were intrahepatic, eight hilar and two extrahepatic (donor bile duct). A control group (n = 32) of patients transplanted immediately before and after index cases was used to examine for correlates in patients with non-anastomotic strictures. At the time of diagnosis in the non-anastomotic index cases, there was a higher incidence of: (i) biliary sludge (63 vs 0%; P < 0.001); and (ii) clinical cholangitis (75 vs 0%; P < 0.001) compared with controls. Primary sclerosing cholangitis was more often the diagnosis in index patients with non-anastomotic strictures compared with controls (31 vs 9%; P < 0.05). There were no differences between index patients and controls (non-anastomotic group) in ABO blood group non-identity, cold allograft ischaemia time, use of OKT3 (murine monoclonal antibody to CD3) and hepatic artery thrombosis. Of 15 patients treated with balloon dilatation, seven required stent insertion although none have required surgery. As determined by liver function tests, there was evidence of persisting graft dysfunction in index patients compared with controls (SAP 381 vs 112 U/L, P < 0.001; GGT 529 vs 80 U/L, P < 0.001), but there was no difference in survival during a median follow-up time of 16 months (range: 3-48 months) from stricture diagnosis. In conclusion, biliary strictures tend to occur within 6 months of transplantation and are an important cause of ongoing graft dysfunction. Non-anastomotic strictures were more common in patients requiring transplantation for primary sclerosing cholangitis.

Adult↗
PubMed1996

Case report: delayed resolution of severe pulmonary hypertension after isolated liver transplantation in a patient with cirrhosis.

Pulmonary hypertension is now recognized to be a rare association of liver disease and portal hypertension. This report describes the slow resolution of symptomatic pulmonary hypertension in a 33-year-old woman with cirrhosis who underwent isolated liver transplantation. The patient survived the surgery and perioperative period without significant haemodynamic compromise. After liver transplantation, the patient was monitored with regular Doppler echocardiography. By 27 months the pulmonary hypertension had almost completely resolved. This observation is important, as it suggests that patients with severe pulmonary hypertension who survive the perioperative period may have an excellent outcome, although resolution may be slow.

Adult↗
PubMed1996

The new age of liver transplantation.

The advent of cyclosporin A for immunosuppression (IS) in liver transplantation (LTx) in the early 1980s heralded a new age for LTx, resulting in widespread application, rapidly expanding indications, relaxation of restrictions in donor selection and advances in the preservation of liver grafts and management of LTx operations. Liver transplantation, together with the transplantation of other organs (kidney, pancreas, heart, heart-lung, intestine), became possible. In Australia, around 125 LTx (22% in children) are performed each year. Indications are: primary sclerosing cholangitis; primary biliary cirrhosis; auto-immune hepatitis; chronic viral hepatitis; biliary atresia; metabolic disorders; fulminant hepatic failure (FHF); alcoholic cirrhosis; and malignancy (cancer, CA). Since 1965, 810 patients underwent LTx and 70 (9%) re-Tx. Patient survivals at 1, 5 and 9 years post-Tx are 80, 74 and 66%, respectively. Patients with primary diseases that recur in the LTx (hepatitis B and CA) do less well following LTx, with 5-year survival rates of 55 and 40%, respectively). Recent developments include: increasing the availability of donor organs by the use of living donors, 'split' cadaveric donor (CD) grafts, 'marginal' and non-heart-beating CD grafts and xenografts; expanding the indications for LTx; development of effective liver support systems for patients with FHF; the treatment of diabetics with liver failure with islet Tx (at the time of LTx); more effective immunosuppression; and methods to diminish recurrent disease in LTx. Some understanding of the unique 'tolerogenic' capabilities of the liver has come with the recognition of 'two-way microchimerism'. The satisfactory 5-9 year outcomes for patients underline the cost-effectiveness of LTx.

Australia↗
PubMed1996

Preclinical trial of a bioartificial liver support system in a porcine fulminant hepatic failure model.

BACKGROUND: This study describes the pre-clinical trials of an extracorporeal bioartificial liver support system (BALSS). It includes the biochemical changes which occur in the plasma and blood of pigs with devascularized livers when the plasma is treated in a BALSS, and the testing of the system for presence or absence of infective agents, pyrogens and for toxicity. METHODS: Hepatic cells were prepared from littermate juvenile white landrace pigs with a double-step collagenase digest technique. The cell preparations were incubated with collagen-coated dextran microspheres (CDM) for 3 h and the medium was tested to determine cellular metabolic activity. Incubation continued for a further 20 h during which the hepatic cells attach to the CDM. The CDM-attached cells were inoculated into a hollow fibre bioreactor which was part of an extracorporeal liver support system. RESULTS: Hepatic cell content of the bioreactor was 6 x 10(9) +/- 3 x 10(8) cells, equivalent to those present in half a pig's liver. The system was tested in a controlled trial with the plasma of pigs with fulminant hepatic failure (FHF) due to devascularized livers. When plasma from FHF pigs was circulated through the device there was significantly less of an increase in the accumulation of ammonia, lactate and most amino acids when hepatic cells were included in the circuit compared with those in control experiments when they were excluded. Similar changes occurred in procine blood. There were few infections diagnosed and an absence of pyrogens, endotoxins and toxicity in the bioreactor contents or in the terminating reservoir or animal blood samples. CONCLUSIONS: We believe that the results, demonstrating function of the porcine hepatic cells in the circuit, together with low risks, justify a clinical trial of use of the BALSS in Australia.

Amino Acids↗
PubMed1995

Deletion of spontaneous rat liver allograft acceptance by donor irradiation.

Liver transplants in rodents or pigs are often spontaneously accepted across a complete MHC mismatch. They induce tolerance to grafts of other organs or skin of liver donor strain and can even suppress ongoing rejection of heart grafts. It has not been established whether liver-induced tolerance is due to components of the liver or to passenger leukocytes within the liver. We depleted populations of passenger leukocytes from the transplanted liver by irradiation of the donor with 10 Gy, followed after 7 days by transplantation of the liver. Recipients of livers from irradiated donors had a median survival of 16 days compared with > 100 days for recipients of livers from normal donors. Examination of recipients of irradiated donor livers showed that allograft rejection was the cause of death. Syngeneic transplants of irradiated PVG donor to PVG recipient or of irradiated DA donor to DA recipient survived indefinitely. Parking of livers from irradiated PVG donors in normal PVG animals for 36 hr reconstituted tolerance when the livers were retransplanted to DA recipients. Livers from irradiated donors had greatly reduced passenger leukocyte numbers compared with normal or parked livers, with virtually complete loss of lymphocytes. These results show that spontaneous liver allograft acceptance is associated with populations of passenger leukocytes that are depleted by donor irradiation.

Animals↗
PubMed1995

Fulminant hepatic failure post liver transplantation: clinical syndromes, correlations and outcomes.

This paper reports the clinical syndrome of fulminant hepatic failure (FHF) following liver transplantation. FHF was defined as the sudden onset of liver failure [encephalopathy and prolonged International Normalised Ratio (INR)] without arterial thrombosis in the setting of a liver allograft. FHf post-transplant was seen in 8/154 (5.2%) adult patients undergoing transplantation. These eight patients developed a clinical syndrome characterised by: (a) a rapid rise in ALT levels to above 1000 U/l (mean maximum 1600 U/l), (b) a sudden increase in the INR to above 5 (mean maximum 5.6), (c) the development of high fever, (d) the persistence of thrombocytopenia (mean nadir 40 x 10(9)/dl), (e) a progressive rise in the bilirubin (mean maximum 400 mumol/l) and (f) the development of hepatic encephalopathy. In seven cases this syndrome occurred following good initial graft function at day 6 post (mean)-transplant. In one case the above syndrome developed immediately after liver transplantation. Four of the eight patients developed multiorgan failure associated with systemic acidosis (mean pH 6.84). All of these patients died (mean day 11). Four patients developed systemic alkalosis. Two of these four patients underwent successful retransplantation (on days 12 and 13) and remain alive at a mean of 11 months post-transplant. Six of the eight patients received OKT3 therapy without any apparent affect on clinical outcome. Compared to control group of patients (n = 28), 8 versus 2/28 had a positive cross-match with donor lymphocytes (P = NS), 1/8 versus 7/28 were ABO-non-identical (P = NS), 3/8 versus 10/21 had total MHC mismatches (P = NS) and 5/7 versus 6/16 had UW ischemic times above 10 h (P = NS). No patients had main hepatic artery thrombosis on angiography although four patients had evidence of intrahepatic microthrombi or arterial necrosis at autopsy. In all cases the histology showed massive haemorrhagic necrosis. Three cases had evidence of veno-occlusive lesions whilst foam cell arteriopathy was seen in two cases. Immunofluorescence was performed in three cases. In two cases there was evidence of immunoglobulin, complement and fibrin deposition in blood vessels. In conclusion, we describe an uncommon clinical syndrome occurring post liver transplant. This syndrome represents humorally mediated allograft rejection but there seems to be no relationship with tissue matching (antibody, ABO, MHC) or donor ischaemic times. If recognised earlier in the absence of multiorgan failure, urgent retransplantation seems to be the only effective therapy.

Acidosis↗
PubMed1994

Tolerance to rat liver allografts. I. Differences between tolerance and rejection are more marked in the B cell compared with the T cell or cytokine response.

Liver allografts in the fully allogenic combination of LEW donor liver to DA recipient (LEW-->DA) are spontaneously tolerated (TOL) with no requirement for immunosuppression, while DA-->LEW allografts are rejected in 12-15 days (REJ). We investigated the mechanism of tolerance induction by identifying differences between TOL and REJ grafts from day 1 to day 9 after transplantation and in normal livers and syngeneic liver graft controls. Infiltrating cell populations were counted after immunohistochemical staining of liver graft sections. There were occasional minor differences between TOL and REJ grafts in the T cell or CD11b/c+ (monocyte/macrophage/granulocyte) infiltrate. In contrast, there was a major difference in B cell infiltrate between TOL and REJ liver grafts. Membrane IgD+ cells were significantly greater in TOL (1796 +/- 225) versus REJ (569 +/- 281) (P = 0.004) portal tracts, as were B220+ cells (1086 +/- 100 vs. 181 +/- 105, P = 0.0004) and CD45RC+ cells (2317 +/- 456 vs. 597 +/- 194, P = 0.004). IgG1, IgG2a, IgM, and IgD deposition in liver allografts, identified by immunohistochemical staining of tissue sections, revealed no IgG or IgD in normal rat liver and low levels of IgM. Deposition of IgG1 was observed in REJ but not in TOL liver on days 7 and 9. IgM was increased in both TOL and REJ liver and appeared to be associated mainly with hepatocytes in REJ and with infiltrate in TOL liver. There was a parallel increase in IgG1-expressing plasma cells in the spleen and lymph nodes of REJ but not TOL animals. Cytokine mRNA was analyzed by reverse transcription and semiquantitative polymerase chain reaction amplification of liver RNA. Increased levels of IL-2, IL-4, IL-6, IL-10, TNF-alpha, transforming growth factor-beta, and IFN-gamma were observed, with similar levels of expression in TOL compared with REJ liver. Cytokine mRNA in syngeneic grafts was not different from normal except for IL-6 and transforming growth factor-beta, which were increased. There is no major difference in the T cell component of the infiltrate or in the extent of upregulation of cytokine mRNA between TOL and REJ grafts. There is a major difference in the B cell compartment, with more B cells in TOL livers and deposition of IgG1 in REJ grafts.

Animals↗