Indications for Mycophenolate Mofetil Therapy in Hepatitis C-Patients Undergoing Liver Transplantation

Platz, K.-P.; Mueller, Andrea; Willimski, C; Mansoorian, Bahareh; Berg, Thomas; Neuhaus, R.; Hopf, U.; Lobeck, H.; Neuhaus, P.

doi:10.1016/s0041-1345(98)00319-4

Cited by 17 publications

(6 citation statements)

References 12 publications

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“…It is conceivable that the anti-HCV effect of MMF is not potent enough to prevent recurrent HCV in patients administered TAC-based immunosuppression. In long-term survivors after LT in whom maintenance immunosuppression is lower, MMF may have antiviral effects, as observed by Platz et al 31 It is possible that in the present study, patients were exposed to a greater level of immunosuppression, which allowed HCV replication at a faster rate. A future study with reduced dosages of steroids and calcineurin inhibitors at the time of introduction of MMF may be able to achieve similar immunosuppression and at the same time offer the antiviral advantages of MMF.…”

Section: Discussionmentioning

confidence: 62%

A prospective randomized trial of mycophenolate mofetil in liver transplant recipients with hepatitis C

Jain

2002

Liver Transplantation

129

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Hepatitis C is the most common indication for liver transplantation (LT) in the United States. Recurrence of hepatitis C virus (HCV) infection post-LT remains a problem for which there is no completely satisfactory treatment. The aim of the present study is to evaluate mycophenolate mofetil (MMF), which has both immunosuppressive and antiviral properties, to determine whether it is associated with a difference in the rate of HCV recurrence and also examine its impact on patient and graft survival. Between August 1995 and May 1998, a total of 106 patients who were HCV positive before LT were randomized to tacrolimus (

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Section: Discussionmentioning

confidence: 62%

A prospective randomized trial of mycophenolate mofetil in liver transplant recipients with hepatitis C

Jain

2002

Liver Transplantation

129

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“…Inhibition of IMPDH results in intracellular guanosine depletion, which is considered to be the antiviral mechanism of MMF against several viruses, including Dengue virus, HBV and HIV-1 as supplement by exogenous guanosine almost fully recovered viral replication (Diamond et al, 2002; Gong et al, 1999; Hossain et al, 2002; Khan et al, 2011; Sebastian et al, 2011; Takhampunya et al, 2006). Clinical studies of MMF effects on HCV have generated inconsistent data (Bahra et al, 2005; Fasola and Klintmalm, 2002; Firpi et al, 2003; Jain et al, 2002; Kornberg et al, 2005; Manrique et al, 2008; Marubashi et al, 2009; Ong et al, 1999; Platz et al, 1998; Rostaing et al, 2000; Zekry et al, 2004). In addition, little is known about the mechanism(s) of the MMF action on HCV.…”

Section: Discussionmentioning

confidence: 99%

“…The clinical effects of MMF on HCV infection, however, are still controversial. Several studies showed that MMF treatment of rejection reduced the incidence of HCV recurrence after liver transplantation (Bahra et al, 2005; Jain et al, 2002; Kornberg et al, 2005; Manrique et al, 2008; Marubashi et al, 2009; Platz et al, 1998), while others reported no change or a slight increase in HCV viral load when MMF was used to treat HCV-infected transplant recipients (Fasola et al, 2002; Firpi et al, 2003; Ong et al, 1999; Rostaing et al, 2000; Zekry et al, 2004). Furthermore, to date, it has not been demonstrated whether MMF has any direct effect on HCV infection/replication in vitro , although a pervious study (Henry et al, 2006) showed that mycophenolic acid (MPA), the active metabolite of MMF, has inhibitory effect on HCV replication in HCV replicon system.…”

Section: Introductionmentioning

confidence: 99%

Mycophenolate mofetil inhibits hepatitis C virus replication in human hepatic cells

Zhang

et al. 2012

Virus Research

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Hepatitis C virus (HCV) infection is the most common indication for liver transplantation and the major cause of graft failure. A widely used immunosuppressant, cyclosporine A (CsA), for people who receive organ transplantation, has been recognized to have the ability to inhibit HCV replication both in vivo and in vitro. In this study, we investigated the effects of several other immunosuppressants, including mycophenolate mofetil (MMF), rapamycin and FK506, on HCV replication in human hepatic cells. MMF treatment of hepatic cells before or during HCV infection significantly suppressed full cycle viral replication, as evidenced by decreased expression of HCV RNA, protein and production of infectious virus. In contrast, rapamycin and FK506 had little effect on HCV replication. Investigation of the mechanism(s) disclosed that the inhibition of HCV replication by MMF was mainly due to its depletion of guanosine, a purine nucleoside crucial for synthesis of guanosine triphosphate, which is required for HCV RNA replication. The supplement of exogenous guanosine could reverse most of anti-HCV effect of mycophenolate mofetil. These data indicate that MMF, through the depletion of guanosine, inhibits full cycle HCV JFH-1 replication in human hepatic cells. It is of interest to further determine whether MMF is indeed beneficial for HCV-infected transplant recipients in future clinical studies.

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“…Early anecdotal reports suggested that MMF might decrease H C V replication in patients with viral recurrence after liver transplantation. 13,20 Despite the absence of supportive data, the routine use of MMF in HCV-infected liver transplant patients became commonplace at some centers in hopes that HCV replication would be suppressed. O u r study in immunocompetent patients with chronic hepatitis C did not show any effect on serum ALT or HCV RNA levels.…”

Section: Discussionmentioning

confidence: 99%

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

Firpi

2003

Liver Transplantation

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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.)

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Indications for Mycophenolate Mofetil Therapy in Hepatitis C-Patients Undergoing Liver Transplantation

Cited by 17 publications

References 12 publications

A prospective randomized trial of mycophenolate mofetil in liver transplant recipients with hepatitis C

A prospective randomized trial of mycophenolate mofetil in liver transplant recipients with hepatitis C

Mycophenolate mofetil inhibits hepatitis C virus replication in human hepatic cells

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

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