Changes in hepatitis C virus RNA viremia concentrations in long-term renal transplant patients after introduction of mycophenolate mofetil.
BACKGROUND
Mycophenolate mofetil (MMF) is a potent immunosuppressive agent and might inhibit chronic rejection, at least in primates. The prevalence of chronic hepatitis C virus (HCV) infection is high in renal transplant (RT) patients. To date, it has not been demonstrated whether MMF has any effect upon HCV viremia.


METHODS
Fourteen long-term HCV(+) RT patients with chronic allograft dysfunction whose maintenance immunosuppression was based on cyclosporine, were given MMF therapy either in place of azathioprine (n=11) or in addition to baseline therapy (n=3). HCV viremia levels were measured by the Amplicor HCV-Monitor RT-PCR assay (Roche Diagnostic Systems) on two separate occasions before the introduction of MMF, and 1 year after changing to MMF or at the last follow-up visit.


RESULTS
MMF therapy was associated with a significant rise in HCV viremia, i.e., 5.8+/-0.5 vs. 5.2+/-0.7 log copies/ml (P=0.01), although there were no significant changes in liver enzymes. The increase in HCV viremia was not related to HCV genotypes either. At the patient level, HCV RNA concentrations changed in only seven patients (group B), i.e. >1 log copies/ml, whereas it remained stable in the others (group A). Before conversion, the only significant difference between group A and B was the level of HCV RNA, i.e., 5.5+/-0.4 log copies/ml in group A and 4.9+/-0.7 log copies/ml in group B (P=0.05).


CONCLUSIONS
Our study suggests that MMF should be used with caution in stable HCV RT patients whose maintenance immunosuppressive therapy is based on cyclosporine, at least in the case of patients with a low HCV RNA titer.
Rostaing
L
L
Multiorgan Transplant Unit, CHU Rangueil, Toulouse, France.
Izopet
J
J
Sandres
K
K
Cisterne
J M
JM
Puel
J
J
Durand
D
D
D000328:Adult; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D018628:Gene Dosage; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000097:blood*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009994:Osmolar Concentration; D012367:RNA, Viral / Q000097:blood*; D013997:Time Factors; D014766:Viremia / Q000097:blood*
D007166:Immunosuppressive Agents; D012367:RNA, Viral; D016572:Cyclosporine; D009173:Mycophenolic Acid