Higher Concentrations of Cyclosporine Metabolites in Liver Transplant Recipients With a History of Viral and Bacterial Infections

Abstract

Background: Infection remains a serious clinical problem in liver transplant (LTX) recipients. A higher risk of infection is connected with immunosuppression therapy. The aim of the study was to assess the relationships between infections' incidence and concentrations of cyclosporine (CsA) metabolites after LTX.

Methods: Forty-three liver transplant recipients receiving CsA were included in the study. With the use of liquid chromatography combined with tandem mass spectrometry, concentrations of CsA and its metabolites were measured: dihydroxylated cyclosporine metabolites (DiHCsA), trihydroxylated cyclosporine metabolites (TriHCsA), demethylcarboxylated cyclosporine metabolites (DemCarbCsA), AM1, AM9, and AM4N. The study protocol conformed with the Declaration of Helsinki.

Results: Patients with a history of Epstein-Barr virus (EBV) infection had higher DiHCsA, TriHCsA, DemCarbCsA, AM1/CsA, DiHCsA/CsA, TriHCsA/CsA i DemCarbCsA/CsA in comparison with group without such infection (P = .049, P = .037, P = .006, P = .018, P = .005, P = .027, and P = .026, respectively). LTX recipients with a history of all viral infections had higher DiHCsA, TriHCsA, DiHCsA/CsA, TriHCsA/CsA than patients without viral infections (P = .013, P = .021, P = .013, and P = .048, respectively). Multivariable analysis showed that AM1, DiHCsA, TriHCsA, DemCarbCsA, AM4N/CsA had positively influence on the incidence of all viral infections (β = 0.0302, P = .0328; β = 0.0699, P = .0453; β = 0.6781, P = .0382; β = 0.6767, P = .0414; and β = 0.8307, P = .0267, respectively). In multivariable analysis, patients with a history of all bacterial infections had higher AM1 and higher AM1/CsA in comparison with LTX recipients without such infections (β = 0.0118, P = .0279; and β = 0.0099, P = .036, respectively).

Conclusion: In liver transplant recipients with a history of viral or bacterial infections higher concentrations of CsA metabolites were found. Possibly CsA metabolites could be used to assess the risk of infection in patients after liver transplantation. It should be confirmed in further investigations.