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We report the use of fluconazole to control primary immunosuppressive management with tacrolimus in a 9-year-old liver transplant recipient. Progressive increases in the doses of both cyclosporin (up to 20 mg/kg/day) and, subsequently, tacrolimus (up to 60 mg/day) failed to maintain immunosuppressive levels of both agents. After excluding poor compliance, drug interactions and analytical problems and identifying poor bioavailability (< 2.6%) and rapid clearance (4.2 l/h), fluconazole (100 mg/day) was initiated to inhibit tacrolimus metabolism and consistent therapeutic blood levels of tacrolimus were achieved. However, graft function had deteriorated irrevocably and retransplantation was performed. Simultaneous use of tacrolimus (5 mg/day) and fluconazole (100 mg/day) maintained immunosuppression after transplantation. Three weeks later, obstruction of the Roux loop caused deteriorating liver function and tacrolimus blood levels fell. After correction at laparotomy, stabilisation was achieved and discharge was possible on 5 mg tacrolimus b.i.d. plus fluconazole (100 mg).

In a micrototoxicity assay, lymphocytes from ten out of sixteen patients with HBsAg-negative chronic active hepatitis have been shown to be cytotoxic to autologous hepatocytes isolated from percutaneous liver biopsies. This cytotoxicity was demonstrable in all six untreated patients but in only four out of ten receiving immunosuppressive treatment, the presence of cytotoxicity showing a significant association with the activity of the disease assessed histologically. The addition of excess purified lipoprotein (LSP), derived from the hepatocyte plasma membrane, blocked the reaction in all cytotoxic cases, indicating that LSP was the major target antigen. Enriched fractions of T cells were cytotoxic in only one case, whereas non-T cell fractions were cytotoxic in the other ten cases investigated in this way. For optimum T cell cytotoxicity, effector and target cells must share histocompatibility determinants and the results of this study using an autologous system show conclusively that the lymphocyte cytotoxicity found in HBsAg-negative chronic active hepatitis is mediated by a non-T cell population. [ABSTRACT FROM AUTHOR]