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

Jain, Ashok Kumar

doi:10.1053/jlts.2002.29763

Cited by 129 publications

(77 citation statements)

References 32 publications

(41 reference statements)

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“…[85][86][87] In a large phase III study of MMF versus azathioprine after liver transplantation, primary immunosuppression with MMF was associated with a reduced incidence of recurrent HCV. 88 However, in a more recent study, MMF neither delayed the onset nor reduced the severity of hepatitis C recurrence. 89 Histamine dihydochloride blocks macrophage production and release of free radicals, thereby protecting T cells and natural killer cells and potentiating their activation by interferon-␣.…”

Section: Future Antiviral Strategiesmentioning

confidence: 99%

Treatment of recurrent hepatitis C

Gane

2002

Liver Transplantation

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Key Points 1. Treatment of established recurrent hepatitis C with interferon-␣ monotherapy does not achieve sustained virologic response (SVR). 2. Treatment of established recurrent hepatitis C with combination interferon plus ribavirin achieves SVR rates of 17% to 27%, but dropout rates approach 30%. 3. Pretransplant prophylaxis against recurrent hepatitis C with combination interferon plus ribavirin is poorly tolerated in patients with decompensated hepatitis C cirrhosis. 4. Posttransplant prophylaxis with combination interferon plus ribavirin prevents both recurrent viremia and hepatitis in 15% to 20% of patients, but dropout rates approach 50%. 5. Hepatitis C virus genotype is the best predictor of response to antiviral prophylaxis and treatment of recurrent hepatitis C. 6. Interferon-␣ therapy is not associated with an increased risk of allograft rejection in liver transplant recipients. 7. Ribavirin therapy is associated with increased hemolysis in liver transplant recipients. 8. Preliminary data suggest pegylated interferon monotherapy will have similar efficacy but better tolerability than combination interferon plus ribavirin. 9. In a recent study, posttransplant immunoprophylaxis with polyclonal hepatitis C immunoglobulin had no effect on recurrent viremia or hepatitis. (Liver Transpl 2002;8: S28-S37.)

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Section: Future Antiviral Strategiesmentioning

confidence: 99%

Treatment of recurrent hepatitis C

Gane

2002

Liver Transplantation

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“…76 Multivariate analysis of another study suggested that MMF was associated with increased risk for graft failure. 77 Sirolimus combined with either cyclosporine or tacrolimus decreased the risk for ACR and steroid-refractory rejection, but caused elevations of alanine aminotransferase and bilirubin levels in HCV-positive transplant recipients.…”

Section: Immunosuppression and Hepatitis C After Oltmentioning

confidence: 99%

The clinical and immunologic impact of using interferon and ribavirin in the immunosuppressed host

Braun

Vierling

2003

Liver Transplantation

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C irrhosis caused by chronic hepatitis C virus (HCV) infection is the leading indication for cadaver and living donor liver transplantation. 1 Recurrent HCV infection, which occurs within days in virtually all allografts, is associated with a 10-to 20-fold increase in serum HCV RNA levels because of enhanced replication stimulated by immunosuppression. 2,3 A majority develop acute hepatitis C 1 to 4 months post-orthotopic liver transplantation (OLT) that is characterized by lymphocytic infiltration and hepatocyte apoptosis. Progression to chronic hepatitis C is associated with: (1) decline in HCV RNA levels observed in the acute phase because of effects of HCVspecific CD4 T helper subtype 1 (T H 1) and CD8 cell responses, (2) profibrotic effects of interferon-␥ (IFN-␥), and (3) proapoptotic effects of increased hepatocyte expression of Fas. 3 Progression of chronic hepatitis C is accelerated in immunosuppressed patients post OLT, resulting in a cumulative probability of cirrhosis in 30% by 5 years. 4 In addition, a minority develop severe, usually fatal, cholestatic hepatitis C within the first 6 months after OLT that is characterized by a direct cytopathic effect of excessive intrahepatic replication of HVC, intrahepatic anti-inflammatory T H 2 cytokine expression, and absence of an HCV-specific immune response. 3 Studies of the impact of different immunosuppressive regimens on recurrent hepatitis C also have been performed in an attempt to reduce hepatitis C progression while preventing acute cellular rejection (ACR). 5 Overall, HCV infection significantly reduces graft and patient survival compared with patients who undergo OLT for non-HCV-related indications. 6 Results of re-OLT are poor, 7 and this is an increasingly unrealistic option in view of the shortage of organ donors.To prevent morbidity and mortality associated with recurrent hepatitis C, many centers have used interferon alfa (IFN-␣) and/or ribavirin (RVN) as either antiviral prophylaxis or treatment of established hepatitis C or hepatitis B. Regimens have ranged from

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“…No beneficial effect of antibodies against interleukin-2 on HCV infection could be confirmed definitely [23]. There are contradictory data in the literature concerning a correlation between the administration of mycophenolate mofetil (MMF) -an inosine monophosphate dehydrogenase (IMPDH) inhibitor -and recurrent HCV infection [24,25]. The effect of sirolimus, given to patients with renal impairment caused by calcineurin inhibitors, on the recurrence of HCV infection is currently being investigated in several centres.…”

Section: Effect Of Immunosuppressive Therapy On Recurrent Hcv Infectionmentioning

confidence: 99%

Treatment of recurrent hepatitis C virus infection in patients after liver transplantation

Lengyel¹,

Tulassay²

2009

Clinical and Experimental Medical Journal

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The main indication for liver transplantation is the final stage of hepatic cirrhosis developed due to hepatitis C virus (HCV) infection. The recurrence of HCV infection after transplantation is a common situation. Recurrent hepatitis C is a progressive disease; in 20% of patients it produces liver cirrhosis without treatment beside immunosuppression within 5 years. Treatment of recurrent HCV infection is the most important factor of survival in patients with transplantation. Based on literary data and their observations, the authors review the factors influencing the progression of recurrent HCV infection. They discuss in details the effect of immunosuppressive therapy, the importance of selecting appropriate immunosuppressive drugs. They review the key points in the diagnosis of recurrent hepatitis C; underline the decisive role of liver biopsy carried out according to protocol in the diagnosis, as well as the hard consultation between specialists of pathology, hepatology and surgery. They demonstrate their observations with the treatment of patients on the waiting list, the results of early pre-emptive treatment of recurrent chronic hepatitis, furthermore treatment modalities and results in patients with histologically proven chronic hepatitis C. The drug of choice for chronic hepatitis C after transplantation is combined therapy with pegylated interferon and ribavirin. This therapy is able to assure sustained virological negativity in 20-50% of patients. In virus-free patients the inflammatory activity in the liver significantly decreases, and the histologic activity index improves. There are data showing a fibrosis-inhibiting effect of the treatment, however, multicentric studies are required for their confirmation. No advantage of early antiviral treatment without histologic alteration has been confirmed by most of the trials. In this group of patients common side effects of the treatment include anaemia and neutropenia, and therefore administration of erythropoietin and granulocyte stimulating factor is recommended. Further research and clinical studies are required in order to establish optimal treatment of patients with recurrent hepatitis C, to determine the dosage of pegylated interferon and ribavirin, to decrease duration of therapy, to reduce side effects and finally to achieve the healing phase in a greater percentage of patients.

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

Cited by 129 publications

References 32 publications

Treatment of recurrent hepatitis C

Treatment of recurrent hepatitis C

The clinical and immunologic impact of using interferon and ribavirin in the immunosuppressed host

Treatment of recurrent hepatitis C virus infection in patients after liver transplantation

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