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G P Fragulidis

Publications and source records attributed to G P Fragulidis.

9 recordsLinked to original sources

In situ enzymatic oligonucleotide amplification of hepatitis C virus-RNA in liver biopsy specimens (reverse transcriptase in situ polymerase chain reaction) after orthotopic liver transplantation for hepatitis C-related liver disease.

BACKGROUND: Hepatitis C infection recurs after orthotopic liver transplantation for hepatitis C virus (HCV)-related end-stage liver disease. Overlapping histopathologic features may present difficulties in differentiating recurrent HCV in the allograft from other conditions, especially rejection. METHODS: In this study, we evaluated the presence of HCV-RNA by reverse transcriptase in situ polymerase chain reaction (RT in situ RCR) in hepatic tissue, after orthotopic liver transplantation for HCV-related liver disease. Further, detection of HCV-RNA was correlated with the serum HCV-RNA levels, histopathology, and clinical outcome. RESULTS: Twenty-five patients were part of this study. Seventeen patients were transplanted for HCV cirrhosis and eight for an underlying disease other than HCV. None of the patients in the non-HCV group had in situ RT-PCR detection of HCV-RNA. Positive RT in situ PCR for HCV was found in 9 of 17 HCV patients, and the patients had a clinical course consistent with recurrent hepatitis C disease. Four of these nine patients had an initial histologic diagnosis of rejection. The other eight patients in the HCV group had negative RT in situ PCR, and none of them had a course compatible with recurrent HCV disease, although four patients were histologically diagnosed as having chronic C hepatitis. The mean HCV-RNA level (log/mL) in the patients who had in situ detection of HCV-RNA was 7.01+/-0.26. Although RT-PCR was negative in 8 of 17 HCV patients, the patients were serologically viremic and the mean HCV-RNA level was 6.05+/-0.33 (P=0.03). CONCLUSIONS: Our findings indicate that the HCV in situ RT-PCR assay may be helpful in the differentiation of recurrent hepatitis C disease from rejection. This may further help in the adjustment of immunosuppression.

Adult↗

Comparison of tacrolimus with microemulsion cyclosporine as primary immunosuppression in hepatitis C patients after liver transplantation.

BACKGROUND: Immunosuppression in patients with hepatitis C virus (HCV) following orthotopic liver transplantation can lead to significant increases in serum viral loads. Our aim was to analyze the effect of a randomized study of two immunosuppressive agents (tacrolimus vs. microemulsion cyclosporine) on the outcome of HCV patients following orthotopic liver transplantation. METHODS: From December 1995 to September 1996, 50 adult patients transplanted for HCV cirrhosis were randomly assigned to receive tacrolimus (Prograf) (group 1, 25 patients) or microemulsion cyclosporine (Neoral) (group 2, 24 patients). All patients received alpha-interferon after transplantation, and the overall steroid doses were no different between the groups. Serum RNA levels were measured by signal amplification of Chiron. Biopsies were taken when transaminases were greater than 2x base line or when there was an inappropriate response to alterations in immunosuppression regimens. RESULTS: There were more episodes of rejection in the Neoral group, but there were no differences in bacterial and viral infections, nor in the rate of HCV recurrence between the two groups. There were seven deaths in group 1 and eight in group 2. Overall patient and graft survival rates in the Prograf and Neoral groups at 18 months were 72 and 68% and 67 and 64%, respectively. CONCLUSIONS: (a) Both immunosuppression regimens had similar HCV recurrence rates; (b) there were no differences in bacterial or opportunistic infections; and (c) patient and graft survival was similar between the two groups.

Adult↗

'Domino' liver transplantation combined with multivisceral transplantation.

Transplantation of the liver contemporaneously with another organ from the same donor is thought to confer an immunologic advantage. The latter is particularly desirable in intestinal transplantation because of the propensity of the intestinal graft to early and late rejections and because in some cases it may facilitate the operation. In clinical practice, shortage of liver grafts constrains liver transplantation to cases in which there is coexisting end stage liver disease.

Adolescent↗

Donor biliary variations: an overlooked problem?

Documented causes of biliary complications following orthotopic liver transplantation have been related to technical imperfections or insufficient arterial supply. Although anatomical variations of the extrahepatic biliary system are not infrequent, neither their incidence, surgical management nor possible association with complications have been reported in liver transplantation. At our institution, the global incidence of biliary complications following 357 consecutive liver transplants performed in 324 patients over a 2-yr period was 15.4% (55/357). Anomalous donor extrahepatic ducts were verified in 10 cases (2.8%) and they were recognized intraoperatively, prior to biliary reconstruction, in 7 cases. Technical complications occurred in 1 of these 7 and in 3 other cases where the anomalous ducts were not identified until later in the postoperative period when serious clinical problems ensued. We herein present a description of these 10 cases, with reference to the techniques employed to manage the anatomical anomalies and to treat complications. As in any hepatobiliary procedure, awareness of possible variations of the extrahepatic biliary system, intraoperative identification of the anomalous ducts and appropriate tailoring of the surgical technique are advisable in order to avoid serious postoperative complications in liver transplantation.

Adult↗

Status of liver and gastrointestinal transplantation at the University of Miami.

The liver transplant program at the University of Miami, established in 1987, was rejuvenated in June 1994 with the addition of new staff and expanded to include all organs of the gastrointestinal tract. Since its inception, 630 patients have been transplanted in the program. During the past 2 years we performed 349 transplants in 318 patients (livers n = 323 in 298 patients, liver + kidneys n = 13, liver + islet n = 10, liver + kidney + islets n = 1, liver + heart n = 10, liver + lung n = 1). These included 4 split-liver, 3 living-related, multiple reduced-sized and one "Domino" liver transplant. We have an active pediatric program and 10% of our transplanted patients are pediatric. Our overall patient and graft survival rates were 81% and 78%, respectively. The intestinal transplant program was launched in August 1994. To date we have performed 22 intestinal transplants, in 9 adults and 13 children. These transplants included 4 isolated intestinal, 11 combined liver-intestinal and 7 multivisceral transplants. Overall patient and graft survival rates were 55% and 50%, respectively. During the past 2 years several studies involving immunosuppressive agents were carried out: 1)Mycophenolate Mofetil (MMF) was used as induction therapy and as rescue therapy in patients with steroid-resistant rejection. Tacrolimus toxicity, and chronic rejection; 2) Neoral was compared with Tacrolimus in patients with Hepatitis C; and 3) MMF was added as triple therapy for the intestinal transplants. We used alpha interferon-2b (alpha-IFN) in hepatitis C positive patients in the early posttransplant period and found that it appears to be a safe drug. There was no increase in rejection in patients receiving alpha-IFN, and patient and graft survival were the same as in our overall patient population. A combination a-IFN with Ribavirin will be undertaken in the near future. The use of Lamivudine in hepatitis B patients was shown to be effective in preventing and treating recurrence of hepatitis B posttransplant. Unmodified donor bone marrow cells (DBMC) were isolated from the vertebral bodies of the same cadaveric liver donors. Donor bone marrow dose, number of cells and/or number (or timing) of infusions were investigated to determine which variables affected the ability of DBMC to engraft in the liver recipient. The long-term benefit of DBMC needs further follow-up. Although, our patient and graft survival for liver transplant recipients is comparable to other large centers nationally and internationally, we still have some challenges to overcome. These include: 1) control and prevention of recurrent HCV, 2) improved treatment for hepatocellular cancer pre- and posttransplant, and 3) treatment and prevention of chronic rejection. Intestinal transplantation remains an even greater challenge. Diagnostic tests to determine intestinal function need further development and although MMF has shown some promise in this field, newer immunosuppressive medications need to be investigated to prevent rejection and avoid over immunosuppression.

Adult↗