Calcineurin inhibition and disease recurrence in the hepatitis C virus-positive liver transplant recipient.
Development of hepatitis C virus (HCV)-related disease following liver transplantation is more aggressive than in non-transplant individuals, and accounts for approximately 10% of liver allograft failures. HCV disease progression appears to have accelerated in recent years, possibly due to the aging donor population and/or changing immunosuppression regimens, and survival among HCV-negative patients is falling. Various risk factors have been proposed for HCV disease recurrence, but choice of calcineurin inhibitor is one of the few that can potentially be modified by the physician. Cyclosporine (CsA) has been shown in vitro to suppress HCV replication as effectively as interferon alpha (IFN-alpha), an effect that is separate from the immunosuppressive activity of CsA. Data from bone marrow patients and non-transplant patient populations confirm that CsA inhibits HCV replication. This anti-HCV effect is not seen with tacrolimus. Histologically, there is evidence that progression of fibrosis in HCV-positive liver transplant patients may be slower with CsA than tacrolimus. The clinical implications of the anti-HCV effect of CsA require evaluation versus tacrolimus in a large-scale multicenter study.
St James's University Hospital, Leeds LS9 7TF, UK. spollard@doctors.org.uk
Stephen
S
Pollard
D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use*; D016174:Hepacivirus / Q000187:drug effects / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016031:Liver Transplantation; D011183:Postoperative Complications / Q000517:prevention & control* / Q000821:virology; D012008:Recurrence; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine