Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Liver disease associated with chronic graft-versus-host disease (cGVHD) is a major cause of mortality and morbidity. Steroids and cyclosporin (CSA), which are the standard therapy, give rather disappointing results, and toxicity is high. Tacrolimus (FK506) is a potent macrolide lactone immunosuppressant that is used in the prevention of solid organ rejection. This study evaluated the therapeutic role of FK506 in the treatment of severe cGVHD-mediated liver disease that did not respond to combined steroids and CSA therapy. Fifteen patients with various hematological disorders who underwent allogeneic stem cell transplantation were enrolled in the study. All patients had severe cholestatic liver disease disturbances and underwent liver biopsy, which was compatible with cGVHD-mediated liver disease. All the patients were negative for markers of chronic liver disease, including viral serology. They received FK506 orally (4-20 mg/day according to serum levels), and were evaluated biweekly by physical examination and liver function tests. Patients were followed for a median of 12 months (range 3-24 months). FK506 treatment ameliorated liver functions in 9 of 15 patients (60%), 5 of whom demonstrated complete normalization of liver enzymes (33%). In 5 patients, no major effect was observed, and 1 patient showed deterioration of his liver functions. Mean GGT levels decreased from 171.5 to 55.6 within 6 months of treatment. Median time to response was 3 months (range 1-11). Side effects were generally transient. Treatment with FK506 was found to be effective in the majority of patients with steroid and CSA-resistant cGVHD-associated liver disease, with manageable side effects. In view of these findings, FK506 may yet evolve into first line therapy for cGVHD induced liver toxicity.
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PMID:Amelioration of steroid-resistant chronic graft-versus-host-mediated liver disease via tacrolimus treatment. 1145 16

Antigens given orally or through the portal vein are known to be less immunogenic and to induce immunologic unresponsiveness. The mechanisms responsible for graft enhancement are still unclear. Moreover, in actuality, it is difficult to perform transfer of donor antigens via the portal vein in clinical transplantation. We investigated the effect of transfer of donor blood via the portal vein intra- and post-operatively in living related donor liver transplantation for recurrent multiple hepatocellular carcinoma. A 62-year-old female, who suffered from recurrent multiple hepatocellular carcinoma with hepatitis C virus, underwent living related donor liver transplantation with the right lobe of her daughter. Eleven hepatocellular carcinomas were recognized in the resected specimen. Donor blood was administered via the portal vein using a catheter inserted in the middle colic vein intra- and postoperatively. Mononuclear cells were obtained by operative liver biopsy or postoperative biopsy using fine needle aspiration biopsy, and from peripheral blood. They were analyzed by two or three color-flow cytometry using several antibodies. The differentiation between donor and recipient was estimated by means of anti-HLA antibodies of donor and recipient. The postoperative course was uneventful. She did not suffer from acute cellular rejection and was discharged on day 30 the after operation. CD56+ CD3+ T cells in the liver increased notably from 20% to 50% after transplantation. One half of the CD56+ CD3+ T cells in the liver graft were of the donor type (donor anti-HLA A2 antibody) on day 8 after surgery. Donor type CD56+ CD3+ T cells occupied 17.4% of the total CD56+ CD3+ T cells even on day 42 after the operation. Stimulation index by mixed lymphocyte reaction continued at a low level (< 2) from day 1 after the operation. Steroids were discontinued after 40 postoperative days. FK506 was also reduced to 0.5 mg/day 4 months after the operation. There was no recurrence of hepatocellular carcinoma and hepatitis C virus for two years after the operation. Macrochimerism of donor type CD56+ CD3+ T cells in a graft might be induced by the transfer of donor blood via the portal vein and may play an important role in transplantation tolerance. Inoculation of donor blood via the portal vein may also be very useful for rapid reduction of immunosuppression.
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PMID:Macrochimerism of donor type CD56+ CD3+ T cells in donor specific transfusion via portal vein following living related donor liver transplantation. 1469 87

In this study, we report a living donor partial pancreas transplantation using intraportal donor-specific leukocyte transfusion (DSLT). The recipient was a 38-year-old woman who had type I diabetes mellitus for 17 years. Hypoglycemia occurred 2 or 3 times per week. Her hemoglobin A1c level was 9.0%, and she required 70 U of insulin almost every day. The donor was her 64-year-old father. The steroid-minimized immunosuppressive protocol included 1.5mg of thymoglobulin administered with a steroid bolus on days 0, 4, and 7 postoperatively. Steroids were never prescribed thereafter. Postoperative maintenance therapy included tacrolimus (FK506) and mycophenolate mofetil. In addition to these conventional approarches, we administered intraportal DSLT on days 0, 1, 4, and 7 after transplantation. The donor-specific leukocytes (40mL) had been separated from donor whole blood using an apheresis filter (Cellsorba EX; Asahi Kasei medical Co, Ltd, Tokyo, Japan). In the recipient operation, a segmental pancreas graft was transplanted into the right iliac cavity with enteric drainage with a pancreatic duct stent. Operation time was 6 hours. The postoperative course was uneventful. The patient was discharged on day 15 after transplantation. There was no acute rejection for six months after transplantation. The hemoglobin A1c level recovered to 5.1% with 6 U of insulin per day. At immunologic analysis, only interleukine-10 cytokine production was elevated at 7 days after transplantation. At flow cytometry cross-match analysis, the immunoglobulin M antibody decreased from day 7 after transplantation. We conclude that intraportal DSLT may be an effective adjunct to a steroid-free regimen.
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PMID:Living related pancreas transplantation alone with enteric drainage in Japan: case report. 1892