Biomedical subjects
B W Shaw
Publications and source records attributed to B W Shaw.
Low incidence of intraspousal transmission of hepatitis C virus after liver transplantation.
Although the incidence of spousal transmission of hepatitis C virus (HCV) in chronic carriers is extremely low (1.4% to 8%), hepatitis C recurrence after liver transplantation is common with markedly increased serum HCV RNA levels. Thus, partners of these patients may be at higher risk of acquiring infection. This study evaluates the prevalence of spousal transmission of hepatitis C after liver transplantation. Twenty-two of 25 couples who were eligible agreed to the retrospective study. Twenty-two patients (17 males, 5 females) and spouses (5 males, 17 females) were studied with respective mean ages of 50.2 years (35 to 65 years) and 46.9 years (33 to 66 years). Liver enzymes, second-generation enzyme-linked immunosorbent assay (ELISA) for antibody to HCV (anti-HCV) and HCV RNA by polymerase chain reaction (PCR), and branched DNA assay were performed. HCV-associated antibodies were detected in 1 of 22 (5%) spouses and 21 of 22 (95%) patients (P < .0001). Nineteen of 22 (86%) patients tested positive by PCR with a mean value of 16,218,100 Eq/mL (464,700 to 51,980,000). All spouses including the only ELISA anti-HCV positive spouse tested negative by PCR (P < .0001). Eight of 21 spouses tested negative for anti-HCV pretransplantation, (13 of 21 pretransplantation were not tested). Estimated mean duration of hepatitis C infection in patients was 14 years (3 to 40 years). Mean patient follow-up posttransplantation was 654.5 days (141 to 1,959 days). Mean duration of marriage was 22.6 years (2.5 to 46 years). No risk factors other than exposure to index patients were observed in spouses. The incidence of spousal transmission of HCV in liver transplantation remains low (5%) and similar to chronic carriers of HCV.
Clinical denouement and mutation analysis of patients with cystic fibrosis undergoing liver transplantation for biliary cirrhosis.
OBJECTIVE: To describe the clinical characteristics of patients with cystic fibrosis considered for liver transplantation and the clinical outcome after transplantation. METHODS: Patient charts were reviewed. Mutation analysis was performed on blood or liver tissue samples with a panel of 17 mutations. RESULTS: Eight patients (five girls) with cystic fibrosis have undergone orthotopic liver transplantation for biliary cirrhosis. Mean age at transplantation was 12.0 years +/- 7.7 years (range, 9 months to 23 years). Preoperatively, seven patients had mild to moderate pulmonary dysfunction and one moderate to severe pulmonary dysfunction. All patients required pancreatic enzyme replacement, and four patients required insulin for diabetes mellitus. The 1-year survival rate was 75%, with no deaths related to septic events. Mean time of follow-up the six operative survivors was 4.1 years +/- 1.9 years. Pulmonary function testing, in those serially tested, showed that forced expiratory volume in 1 second was maintained or improved and that forced vital capacity improved after transplantation. Mutation analysis showed the following genotypes: four patients, delta F508/delta F508; one patient, delta F508/N1303K; and three patients, delta F508/unknown. CONCLUSIONS: Despite the high risk of transplantation, these encouraging results indicate that liver transplantation should be considered for patients with cystic fibrosis and complications of end-stage liver disease. We could not demonstrate an unusual pattern of CF gene mutations in these patients with severe liver disease. It appeared that immunosuppressive agents did not have a deleterious effect on pulmonary function.
Proton spectroscopy of brain glutamine in acute liver failure.
Evidence indicates that the accumulation of glutamine in the brain plays an important role in the pathogenesis and severity of the encephalopathy of acute liver failure (ALF). This study uses in vivo proton magnetic resonance spectroscopy (1H MRS) to assess brain glutamine (GLN) in five cases of acute liver failure. The findings are consistent with prior investigations and suggest that the alpha 1H of the GLN molecule can be used for noninvasive spectroscopic quantitation of brain GLN in patients with ALF.
University of Nebraska Medical Center Liver Transplant Program.
The field of liver transplantation has evolved slowly over the past 5 years. The most important new additions to this field include new immunosuppressive agents and greatly broadened recipient selection criteria. The most compelling problem in transplantation today remains the lack of suitable donors. Innovative surgical techniques, such as auxiliary liver transplantation, extracorporeal support and living-related donation, represent new and important additions to the approach to patients with liver disease.
Transfusion-induced graft-versus-host disease after liver transplantation. Documentation using polymerase chain reaction with HLA-DR sequence-specific primers.
Graft-versus-host disease (GVHD) occurring after liver transplantation can pose a difficult diagnostic dilemma. Similar clinical and pathologic skin and gastrointestinal manifestations can result from other causes (i.e., drugs, infections). Treatment for each of these entities differs, and the high mortality associated with GVHD makes this distinction critical. GVHD has been assumed to result from the cotransplantation of donor lymphoid tissue along with the allograft. In most instances, the patient also receives blood products during the operation, and occasionally during the postoperative period, and the lymphoid cells in these products are also a potential source of concern. In this report, we describe a patient who developed GVHD after liver transplantation. Using molecular diagnostic techniques, we determined that the source for this GVHD was not the organ donor, but was most likely nonirradiated blood products received during the hospital course. Our results suggest that transplant recipients with concomitant hematopoietic dysfunction would benefit from irradiated blood products to reduce the likelihood of this complication.
Survival of graft-versus-host disease in a liver transplant recipient.
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Aplastic anemia after liver transplantation for fulminant liver failure.
We determined the incidence and outcome of aplastic anemia among 56 patients who underwent liver transplantation for fulminant liver failure at the University of Nebraska Medical Center between July 1985 and December 1993. Aplastic anemia developed in 6 of 18 (33%) children and 1 of 19 (5%) adults who had fulminant non-A, non-B hepatitis; no cases of aplastic anemia occurred among patients with other causes of fulminant liver failure. None of these patients had evidence of a preexisting hematological disorder or infection with hepatitis C virus (as determined with a second-generation ELISA). Aplastic anemia was diagnosed at a median of 4 wk after the onset of hepatitis, with five cases seen before transplantation. Six patients received antithymocyte globulin to promote remission of aplastic anemia. Three children died (fungal infection in two, intracranial hemorrhage in one)--one at 43, one at 108 and one at 119 days after transplantation--without remission of aplastic anemia. Among the four surviving patients, with median follow-up of 25 mo, complete and partial remission of aplastic anemia have occurred in three and one, respectively. Liver allograft function is stable in all surviving patients. The data demonstrate that aplastic anemia is a common complication among children who undergo liver transplantation for fulminant non-A, non-B hepatitis. It is associated with a high rate of mortality, although most survivors appear to have full hematological recovery.
Intrahepatic arteriopathy associated with primary nonfunction of liver allografts.
In this report we describe two cases of liver allograft primary non-function in which the donor organs were obtained from patients with a long-standing history of hypertension and placed in normotensive 2 recipients. Examination of these failed grafts showed marked luminal narrowing of the medium and large intrahepatic arteries along with extensive hepatocellular necrosis. No evidence of cellular allograft rejection was present. Preoperative frozen section evaluation of the donor liver failed to detect any pathological changes in the donor organs. Morphometric studies showed a statistically significant luminal narrowing of the medium arteries in these patients compared with controls with graft failure because of other causes (P < .0001). To our knowledge there are no previous reports describing this finding in the literature. We hypothesize that the arterial narrowing in these livers resulted in compromised blood flow to the organ after transplantation into a normotensive patient. Further studies are necessary to determine the frequency of these changes in the hypertensive population. Such studies may lead to the development of criteria that will identify potential donors who are likely to have such changes before organ procurement.
Xenografts: do they have a role?
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Bile acid metabolism and biliary secretion in patients receiving orthotopic liver transplants: differing effects of cyclosporine and FK 506.
Bile acid metabolism and biliary secretion were characterized in the first 2 wk after orthotopic liver transplantation in 15 patients receiving cyclosporine and in five patients receiving FK 506. Analyses were performed on hepatic bile obtained by T-tube drainage; values obtained were compared with literature values for bile samples obtained in patients who had undergone cholecystectomy. Biliary bile acid output, which is equivalent to bile acid biosynthesis from cholesterol, was low (mean +/- S.E.M.) and increased with time: day 1, 0.50 +/- 0.1 mmol/day; day 3, 0.8 +/- 0.1 mmol/day; and day 6, 1.6 +/- 0.5 mmol/day. Chenodeoxycholic acid biosynthesis, as percent of total bile acid biosynthesis, was abnormally low in patients receiving cyclosporine (16.2 +/- 1.1) but not in patients receiving FK 506 (38.2 +/- 4.8) (p < 0.005). Before the T-tube was clamped, the proportion of deoxycholic acid (a secondary bile acid formed by bacterial 7-dehydroxylation of cholic acid) was low in both groups: cyclosporine, 0.4 +/- 0.1; FK 506, 4.8 +/- 2.5 (p < 0.01). The mean concentration of bile acids in hepatic bile between days 4 and 11 did not differ significantly between groups: cyclosporine, 7.7 +/- 1.3 mmol/L; FK 506 4.3 +/- 0.7 mmol/L (mean +/- S.E.M.). (These values are similar to those reported for patients who have undergone cholecystectomy.) Bile acid-dependent bile flow, expressed as apparent choleretic activity (microliters of bile per micromole of bile acid output), was markedly elevated: in patients receiving cyclosporine the value was 129, and in patients receiving FK 506 the value was 220. (In patients who have undergone cholecystectomy, this value is less than 30).(ABSTRACT TRUNCATED AT 250 WORDS)
The origin of lymphocytes in donor-derived lymph nodes following combined liver and small bowel transplantation.
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Effect of cyclosporine dosing on creatinine levels in hepatic transplant recipients.
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A percutaneous method for venovenous bypass in liver transplantation.
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Epstein-Barr virus hepatitis after liver transplantation.
OBJECTIVES: The purpose of this study was to review our experience with Epstein-Barr virus (EBV) hepatitis after liver transplantation. METHODS: During a 68-month period, we performed 668 liver transplants and 585 patients. We identified 11 patients (2 percent), including 5 adults and 6 children with EBV hepatitis after liver transplantation. The diagnosis of EBV hepatitis was established by evaluating allograft biopsies. The histology was confirmed by the use of polymerase chain reaction technology. RESULTS: The average time of diagnosis after liver transplantation was 45 days. Eight of eleven cases occurred within the first six months after transplantation. After the diagnosis of EBV hepatitis, treatment consisted of a decrease in immunosuppression plus antiviral therapy and intravenous immunoglobulin. The one-year actuarial survival for patients with EBV hepatitis, was 73 percent (8 of 11). Two patients died of progressive multi-organ EBV involvement. To determine the risk of developing EBV hepatitis, we reviewed our experience with the administration of antilymphocyte preparations in 585 patients. The patients found to have a significantly greater risk of developing EBV hepatitis included those receiving more than one course of antilymphocyte therapy or greater than a total dose of 70 milligrams of OKT3 in a single course. CONCLUSIONS: EBV hepatitis after liver transplantation is an infrequent event, which may be treated successfully. The occurrence of EBV hepatitis appears closely linked to the use of antilymphocyte preparations.
The nature of complications following liver biopsy in transplant patients with Roux-en-Y choledochojejunostomy.
Liver biopsy is an important diagnostic tool in the management of patients following orthotopic liver transplant. We evaluated complications following percutaneous liver biopsy in a group of liver transplant patients who had Roux-en-Y choledochojejunostomies fashioned as part of their biliary reconstruction during liver transplantation. Complications were divided into two major groups: septic complications (including fever, symptomatic bacteremia, cholangitis, infected hematoma and hypotension related to sepsis) and bleeding (defined as hypotension requiring volume expansion greater than 500 cm3 or blood transfusion, hemothorax, intrahepatic or peritoneal hemorrhage and hemobilia occurring within 1 wk of liver biopsy). One hundred ninety-two biopsies were performed in 46 patients with choledochojejunostomies, and 118 biopsies were carried out in an age- and sex-matched control group of patients with choledochocholedochostomy biliary anastomosis. There were no septic complications in the choledochojejunostomy patients and one (0.32%) septic complication in the choledochocholedochostomy patients (NS). Eight bleeding complications occurred (2.6%) in eight patients (8.3%). Five (2.6%) occurred in five (10.8%) of the choledochojejunostomy patients, vs. three (2.5%) in three (6.5%) choledochocholedochostomy patients (NS). None of the bleeding complications required surgical intervention or was fatal. We conclude that liver biopsy in posttransplant patients with Roux-en-Y choledochojejunostomies is a safe procedure and that the incidences of complications were similar in our two groups. The negligible incidence of septic complications in the choledochojejunostomy patients does not appear to warrant the administration of prophylactic antibiotics, as has been previously suggested.
Preoperative evaluation of donor liver volume in pediatric living related liver transplantation: how accurate is it?
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