title: Increased susceptibility for CsA-induced hepatotoxicity in kidney graft recipients with chronic viral hepatitis C.
abstract: CsA-induced hepatotoxicity is a rare disorder in renal transplant recipients when low doses are administered and whole blood trough levels of CsA are regularly monitored. However, there is controversy about the clinical value of measuring CsA-metabolites, whose contribution to immunosuppression and toxicity is not fully understood. To assess the relation between low-dose CsA therapy and hepatotoxicity, we studied 128 renal transplant recipients attending our nephrology clinic. Eight of these patients had markedly elevated liver function tests. Three patients while receiving very low doses of oral CsA (< 3.8 mg/kg of body weight) presented marked derangements of CsA metabolism with abnormally increased CsA-metabolite levels. Parent drug levels were in the normal range. All 3 patients had chronic infection with hepatitis C virus and revealed histomorphologic evidence of hepatotoxicity. Hepatic dysfunction normalized when CsA was withdrawn or reduced by 50%. It is likely that hepatitis C virus infection interferes with CsA metabolism and/or biliary CsA-excretion and thus is responsible for CsA and/or metabolite-induced hepatotoxicity despite very low doses of CsA.
authors.affiliation: Department of Medicine, Karl Franzens University, Graz, Austria.
authors.forename: J H
authors.initials: JH
authors.lastname: Horina
authors.forename: G H
authors.initials: GH
authors.lastname: Wirnsberger
authors.forename: L
authors.initials: L
authors.lastname: Kenner
authors.forename: H
authors.initials: H
authors.lastname: Holzer
authors.forename: G J
authors.initials: GJ
authors.lastname: Krejs
mesh_terms: D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D002908:Chronic Disease; D016572:Cyclosporine / Q000009:adverse effects* / Q000378:metabolism; D004198:Disease Susceptibility; D006526:Hepatitis C / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D016030:Kidney Transplantation; D008111:Liver Function Tests; D012189:Retrospective Studies
chemical_list: D016572:Cyclosporine