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Transplantation Proceedings 09/2002; 34(5):1976-8. · 1.00 Impact Factor
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ABSTRACT: Pediatric allograft recipients are at increased risk for Epstein-Barr virus (EBV)-associated illnesses. The early identification and diagnosis of EBV-associated disorders is critical because disease progression can often be curtailed by modification of immunosuppression. We have previously shown that detection of EBV-specific sequences in the circulation by polymerase chain reaction (PCR) correlated well with the clinical symptoms of EBV infection. The purpose of the current study is to determine the significance of detecting EBV-specific sequences by PCR in asymptomatic pediatric liver transplant recipients. Peripheral-blood DNA was analyzed for the EBV genes, coding from the nuclear antigen 1 (EBNA-1) and the viral capsid antigen (gp220) by PCR. Samples from asymptomatic pediatric liver transplant recipients were analyzed from the immediate postoperative period and at 2- to 4-month intervals thereafter. We followed up 13 of these asymptomatic recipients who tested positive for EBV compared with 7 asymptomatic recipients who tested negative for EBV during the early posttransplantation period. Follow-up ranged from 1.5 to 4 years posttransplantation. Nine patients (69%) initially positive for EBV and asymptomatic ultimately developed symptoms of EBV infection, including fever, lymphadenopathy, rash, respiratory and gastrointestinal symptoms, and/or hepatitis. Five of these patients (56%) went on to develop posttransplant lymphoproliferative disorder based on histological examination of biopsied tissue and immunohistochemical identification of the EBV antigen/DNA in tissue. This is the first report suggesting that detection of EBV-specific sequences in the absence of symptoms may herald impending EBV-associated disorders. Thus, routine monitoring for circulating EBV sequences in asymptomatic recipients may be useful in the early identification of those at risk for developing EBV-associated disease and its ultimate prevention.
Liver Transplantation 02/2000; 6(1):62-6. · 3.39 Impact Factor
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ABSTRACT: Epstein-Barr virus (EBV) infection is common after liver transplantation in children and is associated with the risk of posttransplant lymphoproliferative disorders (PTLD).
This retrospective study examined the frequency of gastrointestinal (GI) symptoms and the risk of PTLD in pediatric liver recipients who developed symptomatic EBV infection. We reviewed 172 children who received orthotopic liver transplants between March 1988 to December 1994. Twenty-two cases were retransplants. The mean age at transplantation was 3.7 years (range, 0.1-17 years). The immunosuppressive regimens consisted of induction therapy with Minnesota antilymphocyte globulin/antithymocyte globulin/OKT3 in most cases and maintenance therapy with prednisone and either cyclosporine or tacrolimus (FK506).
After 1 year of minimum follow-up, 54 of 172 patients had symptomatic EBV infections (confirmed by serology, histology, or whole blood polymerase chain reaction. At the time of infection, 38.5% (21/54) had either diarrhea or GI bleeding or both. PTLD developed in 11 patients (6.4%). The incidence of PTLD was 42.9% (9/21) when GI bleeding or diarrhea was associated with EBV infections, compared with 6.1% (2/33) when EBV infection was not associated with GI symptoms. Seven of 10 (70%) patients with GI bleeding and 2 of 11 (18.2%) with diarrhea developed PTLD. Of seven patients examined by endoscopy for GI bleeding, two had biopsy-proven PTLD of the GI tract, whereas one of two patients examined by endoscopy for diarrhea had biopsy-proven PTLD.
In summary, a high incidence of PTLD was found in patients who developed GI bleeding or diarrhea associated with EBV infection after pediatric liver transplantation. In these patients, endoscopy and biopsy may lead to early diagnosis of PTLD.
Transplantation 11/1998; 66(7):851-6. · 4.00 Impact Factor
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Transplantation 05/1998; 65(5):164. · 4.00 Impact Factor
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ABSTRACT: Recent advancements in liver transplantation have resulted in extended survival both for grafts and recipients. Such improvement, together with the shortage of donor organs has prompted expansion of the donor pool to include less than ideal donors, especially in life-threatening situations. The use of older liver donors has been associated with lower long-term survival. However, potential morbidity such as gallstone formation has not been explored. We analyzed bile composition in a child who developed cholesterol gallstones in the proximal bile duct two years after undergoing emergency liver transplantation with a liver from a 78-year-old donor. Oral administration of ursodeoxycholic acid (ursodiol) shifted the cholesterol composition of the bile from a supersaturated, potentially crystallized state to a liquid (micellar) state. Unlike cyclosporin A, FK506 showed an increase in the proportion of chenodeoxycholic acid and a decrease in the proportion of cholic acid, and thus may exhibit minimal or no hepatotoxic effect. Thus, in donor livers with factors known to be associated with cholesterol gallstone formation (such as age, sex, or obesity), one may consider analyzing the bile composition at the time of procurement. Depending on cholesterol and bile acid composition the use of FK506 with or without addition of ursodeoxycholic acid may be warranted.
Digestive Diseases and Sciences 08/1997; 42(7):1409-15. · 2.12 Impact Factor
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ABSTRACT: A male infant with neonatal iron storage disease, also known as neonatal hemochromatosis (NH), underwent orthotopic liver transplantation (OLT) at the age of 55 days. The native liver contained an incidental hepatocellular carcinoma. Scant iron accumulation was found in a biopsy specimen of the implanted liver on the seventh postoperative day (POD); successive biopsies showed increasing siderosis. On POD 62, the patient died of a cardiac arrhythmia. Autopsy showed siderosis at many sites, including the implanted liver. We discuss the possibility that hemochromatosis recurred in the liver allograft and review possible factors contributing to the siderosis.
Transplantation 12/1996; 62(10):1511-3. · 4.00 Impact Factor
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ABSTRACT: The present study examined 144 pediatric liver transplants to determine the impact of ABO matching on liver allograft outcome. Pediatric transplants were divided into 3 groups: ABO identical (ABO-Id; n = 108), ABO-compatible nonidentical (ABO-Comp; n = 22), and ABO incompatible (ABO-Inc; n = 14). A higher proportion of United Network for Organ Sharing status 4 recipients in the ABO-Comp group (50% vs. 22% and 36% for ABO-Id and ABO-Inc, P < 0.05) and less time spent on the waiting list for ABO-Inc recipients (46 +/- 12 vs. 87 +/- 11 and 61 +/- 20 days for ABO-Id and ABO-Comp, P < 0.01) were noted. OKT3 induction therapy was greater in ABO-Inc grafts (57% vs. 19% and 14% for ABO-Id and ABO-Comp, P < 0.05), as was incidence of acute cellular rejection (79% vs. 59% and 41% for ABO-Id and ABO-Comp, P = 0.08). One- and 3-year patient survival rates were 87% and 83% in the ABO-Id group, 95% and 88% in the ABO-Comp group, and 79% and 79% in the ABO-Inc group (P = NS). One- and 3-year graft survival rates were 83% and 78% in the ABO-Id group, 87% and 80% in the ABO-Comp group, and 71% and 71% in the ABO-Inc group (P = NS). ABO-Inc transplantations can be performed successfully in pediatric recipients and warrant a reassessment of the utilization of ABO-Inc livers.
Transplantation 10/1995; 60(7):757-60. · 4.00 Impact Factor
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Transplantation 04/1995; 59(5):791-3. · 4.00 Impact Factor
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Transplantation Proceedings 03/1995; 27(1):1146-7. · 1.00 Impact Factor
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Transplantation Proceedings 03/1995; 27(1):1211-2. · 1.00 Impact Factor
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ABSTRACT: During allograft rejection, adhesion molecules play an integral role in infiltration, activation, and binding of effector cells to target tissue. Some adhesion molecules, including ICAM-1 and VCAM-1, exist in soluble, circulating forms that retain ligand-binding activity. In the present study the levels of circulating ICAM-1 (cICAM-1) and VCAM-1 (cVCAM-1) were compared in the serum and bile of pediatric liver recipients. The cICAM-1 was significantly elevated in the serum during allograft rejection and infection relative to periods when no rejection was apparent. Biliary cICAM-1, however, was specifically elevated during rejection and not during infection or when no rejection was apparent. The cVCAM-1 levels were elevated in the serum during rejection compared with levels when no rejection was evident. In contrast, cVCAM-1 was not detected in the bile. Serum levels of both cICAM-1 and cVCAM-1 decreased rapidly following successful treatment for rejection, whereas elevated levels persisted, or increased, in ongoing rejection. The differential patterns of the circulating forms of ICAM-1 and cVCAM-1 were consistent with the membrane expression of these molecules during graft rejection. ICAM-1 expression was extensive on bile duct epithelium, endothelium, hepatocytes, and infiltrating leukocytes during rejection, while VCAM-1 was restricted to endothelium. These findings indicate that the release of circulating adhesion molecules is a prominent feature of liver allograft rejection. Measurement of these markers may be useful in distinguishing rejection from infection and in determining the efficacy of treatment for rejection.
Transplantation 03/1995; 59(4):584-9. · 4.00 Impact Factor
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Transplantation Proceedings 03/1995; 27(1):1239-40. · 1.00 Impact Factor
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ABSTRACT: Pediatric allograft recipients in particular are at increased risk for Epstein-Barr virus (EBV)-associated disorders. Early identification and diagnosis of EBV-associated disorders is critical, since disease progression can often be halted by reduction of immunosuppression. In this study we examined viral and immunologic parameters of EBV infection in the circulation of pediatric liver recipients to identify factors associated with disease. Peripheral blood DNA from pediatric liver recipients was analyzed by PCR for the EBV genes coding for the nuclear antigen 1 (EBNA-1) and the viral capsid antigen gp220. Sequences for these viral genes could be readily detected in the circulation of 36.5% of patients. Moreover, identification of the EBV genome was associated with symptomatic infection, suggesting that circulating EBV may be a useful marker of disease. Since EBV-infected B cells release the low-affinity IgE receptor (sCD23), we measured sCD23 in the circulation of pediatric liver recipients and found it to be elevated in patients with detectable virus or symptoms of infection. However, sCD23 was also elevated in cases where no EBV was detectable, suggesting that factors other than viral infection could stimulate release of sCD23. To further characterize the immune response to EBV infection, the peripheral levels of IL-4, IL-5, IL-10, and IFN-gamma were determined in pediatric liver recipients. Each of these cytokines was elevated in patients with symptoms or circulating virus compared with stable, age-matched liver recipients. IL-4, in particular, was significantly increased, indicating an important role for this cytokine in EBV infection. Together, these findings suggest that (1) monitoring circulating levels of EBV may be useful in patients at high risk and (2) cytokines that promote B cell growth and differentiation contribute to EBV-associated disorders.
Transplantation 03/1995; 59(4):519-24. · 4.00 Impact Factor
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Journal of Pediatric Gastroenterology and Nutrition 06/1994; 18(4):494-6. · 2.30 Impact Factor
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ABSTRACT: The safety and efficacy of conversion to FK506 after failing immunosuppression with cyclosporine was prospectively evaluated in 31 pediatric liver transplant recipients between April 1991 and March 1993. The patients, who ranged in age from 40 days to 14 years, accounted for 28 primary transplantations and 3 retransplantations. The initial immunosuppression regimen consisted of cyclosporine in combination with prednisone. The indications for conversion were acute or chronic rejection refractory to OKT3, Minnesota antilymphocyte globulin, or steroids (13 patients); hypertension (8 patients); inability to reach a therapeutic level of cyclosporine (6 patients); hirsutism (3 patients); and growth retardation (1 patient). After an average follow-up of 10 months (range, 2 to 25 months), 27 (87%) of the patients are alive and have functioning grafts. Of the 13 patients who were converted for refractory rejection, 9 are alive. Six of these 9 patients experienced a complete biochemical reversal of the rejection process within 3 months of conversion; 2 had a partial response to conversion, and 1 patient failed but underwent successful retransplantation. Three of the 4 patients who died did so without showing any improvement. The remaining 18 patients who were converted for various other reasons are alive and have functioning grafts. Of the 8 patients who developed hypertension on cyclosporine and prednisone, 6 experienced a resolution of this problem within 3 months of conversion. Three of the 18 children who underwent rescue therapy for reasons other than refractory rejection experienced rejection episodes after conversion to FK506. Two of these 3 children achieved resolution with either steroid therapy or an increased dosage of FK506, while the third child developed chronic rejection. The side effects of FK506 were generally minor and resolved by lowering the dose. Lymphoproliferative disease developed in 2 patients (6%). The present study suggests that FK506 is a relatively safe and effective rescue therapy for pediatric liver transplant recipients who have failed immunosuppression with cyclosporine. Longer follow-up is needed to assess the effect of FK506 on growth.
Transplantation 05/1994; 57(8):1169-73. · 4.00 Impact Factor
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Transplantation Proceedings 05/1993; 25(2):1935-7. · 1.00 Impact Factor
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ABSTRACT: The detection of antibody to the hepatitis C virus C100-3 antigen from the nonstructural region (NS3/NS4) of the viral genome was the first useful marker developed to detect past or potentially active infection with the hepatitis C virus. A systematic epitope survey of the nonstructural region has uncovered other immunogenic antigens. In order to assess the possible diagnostic utility of these antigens, their reactivity against a limited panel of sera from patients with chronic liver disease due to hepatitis C virus and other etiologies was tested. Antibody assays were performed using an immunoblot plaque assay and an enzyme-linked immunosorbent assay (ELISA). In a study of 16 C100-3-reactive individuals, all 16 patients were reactive using the plaque assay for the NS3 3' (409-1-1) and NS3 5' (C33u). In this same group of patients, antibodies by ELISA were reactive to NS3 3' in 12 of 16 patients (75%), NS3 5' in 15 of 16 patients (93%), and a capsid antigen (NC450) in 14 of 16 patients. In a group of five patients who were diagnosed with cryptogenic liver disease (C100-3 negative), 4 of 5 patients were reactive for antibody to all of the above epitopes. In a survey of 23 patients with other forms of chronic liver disease (nonviral liver disease, hepatitis B, alcoholic liver disease, cholestatic liver disease, and autoimmune hepatitis), only 1 of 23 patients was reactive for antibody to the C100-3 and 4 of 23 patients were reactive for antibodies to structural and nonstructural regions of the virus.(ABSTRACT TRUNCATED AT 250 WORDS)
Viral Immunology 02/1993; 6(1):49-54. · 1.97 Impact Factor
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Transplantation Proceedings 01/1992; 23(6):3019-20. · 1.00 Impact Factor
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ABSTRACT: Between March 1988 and November 1989, 100 liver transplants were performed on 90 patients at Pacific Presbyterian (now California Pacific) Medical Center in San Francisco. The immunosuppressive regimen was a combination of prophylactic Minnesota antilymphocyte globulin, cyclosporine, and low-dose corticosteroids. Rejections were treated with OKT3, a monoclonal antibody, or corticosteroids. Of the 100 transplants, 32 were done on 30 children, 18 of whom weighed less than 10 kg and 9 of whom received livers that had been surgically reduced in size to fit the recipient. The overall patient survival at 2 years was 85%. Of 100 liver transplants, treatment was given for 80 (80%) for at least 1 episode of rejection. At least 1 episode of serious infection occurred in 34 of the 60 adult patients and 25 of the 30 children. Of the entire group, 2% had hepatic artery thrombosis, and 12% had biliary complications that necessitated reoperation. The quality of life has been good, with a follow-up from 1 to almost 3 years (mean = 22 months). Comparing these data with those of other published series shows a decreased incidence of surgical complications and a lower rate of fungal and viral infections. We attribute this to the reduction of steroid dosage during convalescence without jeopardizing patient or graft survival.
Western Journal of Medicine 12/1991; 155(5):494-9.
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ABSTRACT: Reduced-size liver transplantation (RSLT) in children was introduced to alleviate a shortage of small-organ donors. The impact of RSLT on the waiting time for an organ and on morbidity and mortality was investigated. Between March 25, 1988, and August 11, 1990, 61 hepatic transplantations were performed in 55 children at the Pacific Transplant Institute in San Francisco, Calif. Full-size liver transplantation was performed in 41 cases and RSLT in 20 cases. The overall 30-month actuarial patient and graft survival rates were 89% and 73%, respectively. A comparison between full-size liver transplantation and RSLT showed no difference in patient and graft survival, reoperations, infections, or rejection. Benefits of RSLT were an increase in the donor pool size, a decrease in waiting time for a suitable donor, and a decrease in the rate of arterial thrombosis. The main morbidity of RSLT was an increase in perioperative blood requirement. We conclude that RSLT offers small children with end-stage liver disease a chance for long-term survival.
Archives of Surgery 11/1991; 126(10):1278-85; discussion 1285-6. · 4.24 Impact Factor
