Lack of antiviral effect of a short course of mycophenolate mofetil in patients with chronic hepatitis C virus infection

Abstract

Mycophenolate mofetil (MMF) is an immunosuppressive agent that is widely used in the management of liver transplant recipients. MMF inhibits the inosine monophosphate dehydrogenase that has been shown to have in vitro antiviral properties against flaviviruses, suggesting the possibility that it might also inhibit the hepatitis C virus (HCV). The goal of this short-term dose escalation study was to assess the antiviral effects of MMF on HCV replication. Patients with chronic hepatitis C who had not undergone liver transplantation were randomized to 8 weeks of treatment with one of four mycophenolate dose regimens (1 000 mg orally twice daily, 500 mg orally twice daily, 250 mg orally twice daily, or a matched oral placebo twice daily). All groups were double-blinded. Quantitative HCV RNA levels and serum alanine aminotransferase were assessed at baseline, at weeks 2, 4, and 8 of dosing, and at weeks 4 and 8 of follow-up. Thirty patients met inclusion criteria, enrolled, and were randomized. HCV RNA levels did not change significantly during treatment.Specifically, no subject became virus negative or had a one-log decrease in virus level. Serum aminotransferase level did not normalize in any subject. The most common side effects were headache, nausea, and diarrhea. Mycophenolate alone does not appear to have a significant antiviral or biochemical effect in patients with chronic hepatitis C. (Liver Transpl2003;9:57-61.)

Recurrent Hepatitis C Virus (Genotype 4) Infection after Living Donor Liver Transplantation: Risk Factors and Outcome

“…Francisco and associates in 2006 [10], found significant correlation between MMF, and low HCV recurrence. On the other hand, several authors reported that MMF administration was not associated with low HCV recurrence [18]. Similarly, in the present study we did not show significant correlation between MMF administration, and disease recurrence.…”

Impact of immunosuppression on immunopathogenesis of liver damage in hepatitis C virus-infected recipients following liver transplantation

“…MMF has been associated with an increase, rather than decrease, in HCV viral loads after renal transplantation, 36 whereas no effect on viral load in the non-liver transplantation situation has been observed. 37 We also showed that a switch from azathioprine to MMF therapy in the presence of low-dose steroids and cyclosporine was associated with an increase in viral load after 3 months of therapy. 38 Furthermore, use of an anti-IL-2 receptor mAb and MMF has been associated with greater viral loads and more liver damage at 4 and 12 months posttransplantation.…”

Acetylsalicylic acid inhibits hepatitis C virus RNA and protein expression through cyclooxygenase 2 signaling pathways

“…Indeed, contradictory results have been reported on the association of interferon-␣ with NSAIDs in treated patients, but they used different pharmacological agents and times of evaluation. [34][35][36][37] Some reports have indicated the failure of NSAIDs and interferon combination therapy in improving interferon-resistant chronic hepatitis C, 34,38 whereas other authors, using ketoprofen plus interferon, have reported an improved virological response in chronic hepatitis C patients. 35 Giambartolomei et al 39,40 reported that indomethacin potentiates the interferon-␣ signaling pathway by increasing signal transducer and activator of transcription 1 phosphorylation in vitro, improving cellular response.…”