The Use of Cyclosporine for Recurrent Hepatitis C After Liver Transplant: A Randomized Pilot Study

Firpi, Roberto J.; Soldevila-Pico, Consuelo; Morelli, Giuseppe; Cabrera, Roniel; Levy, Cynthia; Clark, Virginia; Suman, Amitabh; Michaels, Anthony; Chen, Chaoru; Nelson, David R.

doi:10.1007/s10620-009-0981-3

Cited by 52 publications

(47 citation statements)

References 29 publications

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“…73 Recently, a pilot study from Firpi et al randomized 38 patients with HCV recurrence treated with TAC to either continue TAC or switch to CSA before initiation of PEG-IFN/ RBV. 74 A modest HCV-RNA drop with a trend toward better virologic responses in the CSA group was observed; although statistical significance was not reached. 74 Taken together, the impact of CSA on HCV recurrence or on antiviral therapy response appears to be neutral or beneficial.…”

Section: Immunosuppressive Regimensmentioning

confidence: 91%

“…74 A modest HCV-RNA drop with a trend toward better virologic responses in the CSA group was observed; although statistical significance was not reached. 74 Taken together, the impact of CSA on HCV recurrence or on antiviral therapy response appears to be neutral or beneficial. 4 Therefore, the utilization of CSA in all HCV+ LT recipients must be deliberated with the caveat that TAC appears to be an overall better immunosuppressive agent.…”

Section: Immunosuppressive Regimensmentioning

confidence: 91%

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Management of Hepatitis C Before and After Liver Transplantation in the Era of Rapidly Evolving Therapeutic Advances

Bunchorntavakul¹,

Reddy²

2014

JCTH

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Management of hepatitis C (HCV) in liver transplantation (LT) population presents unique challenges. Suboptimal graft survival in HCV+ LT recipients is attributable to universal HCV recurrence following LT. Although eradication of HCV prior to LT is ideal for the prevention of HCV recurrence it is often limited by adverse events, particularly in patients with advanced cirrhosis. Antiviral therapy in LT candidates needs careful monitoring, and prophylaxis with HCV antibodies is ineffective. Early antiviral therapy after LT has been investigated, but no clear benefit has been demonstrated. Protocol liver biopsy is generally recommended in HCV+ LT recipients, and antiviral therapy can be considered in those with severe/ progressive HCV recurrence. Sustained virological response (SVR) can be achieved in approximately 30% of LT recipients with pegylated interferon/ribavirin (PEG-IFN/RBV) with survival benefit, but adverse effects are common. Favorable patient characteristics for response to therapy include non-1 genotype, previously untreated, low baseline HCV-RNA, and donor IL28B genotype CC. Direct acting antiviral (DAA)-based triple therapy is associated with higher rates of SVR, but with similar or slightly higher rates of side effects, and immunosuppressive regimens need to be closely monitored and adjusted during the treatment period. Notably, the safety and efficacy of HCV treatment are very likely to improve with newer generation DAA. The benefit of immunosuppressive strategy on the natural history HCV recurrence has not been well elucidated. Based upon available evidence, cyclosporine A (CSA), mycophenolate mofetil (MMF), and sirolimus appear to have a neutral or small beneficial impact on HCV recurrence. Donor interleukin 28 B (IL28B) polymorphisms appear to impact the course and treatment outcomes in recurrent HCV. Retransplantation should be considered for patients with reasonable survival probability.

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Section: Immunosuppressive Regimensmentioning

confidence: 91%

Section: Immunosuppressive Regimensmentioning

confidence: 91%

Management of Hepatitis C Before and After Liver Transplantation in the Era of Rapidly Evolving Therapeutic Advances

Bunchorntavakul¹,

Reddy²

2014

JCTH

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“…Furthermore, SVR after IFN therapy has been found to be higher with CsA compared to tacrolimus (46% vs 27%; P = 0.03) [105] . In a pilot study [106] , 38 patients with HCV recurrence receiving PEG IFN α2a and Ribavirin were randomized to continue tacrolimus or to be switched to CsA. CsA led to a modest decrease in HCV RNA levels and appeared to enhance the antiviral response to IFN and Ribavirin, but there was no difference in SVR.…”

Section: Calcineurin Inhibitorsmentioning

confidence: 99%

Strategies to reduce hepatitis C virus recurrence after liver transplantation

Ciria

Pleguezuelo²,

Khorsandi³

et al. 2013

WJH

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Hepatitis C virus (HCV) is a major health problem that leads to chronic hepatitis, cirrhosis and hepatocellular carcinoma, being the most frequent indication for liver transplantation in several countries. Unfortunately, HCV re-infects the liver graft almost invariably following reperfusion, with an accelerated history of recurrence, leading to 10%-30% of patients progressing to cirrhosis within 5 years of transplantation. In this sense, some groups have even advocated for not retransplanting this patients, as lower patient and graft outcomes have been reported. However, the management of HCV recurrence is being optimized and several strategies to reduce post-transplant recurrence could improve outcomes, decrease the rate of re-transplantation and optimize the use of available grafts. Three moments may be the focus of potential actions in order to decrease the impact of viral recurrence: the pretransplant moment, the transplant environment and the post-transplant management. In the pre-transplant setting, it is not well established if reducing the pre transplant viral load affects the risk for HCV progression after transplant. Obviously, antiviral treatment can render the patient HCV RNA negative post transplant but the long-term benefit has not yet been fully established to justify the cost and clinical risk. In the transplant moment, factors as donor age, cold ischemia time, graft steatosis and ischemia/reperfusion injury may lead to a higher and more aggressive viral recurrence. After the transplant, discussion about immunosuppression and the moment to start the treatment (prophylactic, pre-emptive or once-confirmed) together with new antiviral drugs are of interest. This review aims to help clinicians have a global overview of posttransplant HCV recurrence and strategies to reduce its impact on our patients.

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“…In 38 HCV recipients randomized to continue Tac, or switch to CyA, the latter led to a modest reduction of HCV RNA titre and appeared to enhance the response to PEG IFN/ribavirin [32]. A randomized trial [33] of 81 recurrent HCV recipients evaluated disease progression using paired liver biopsies and HVPG measurements.…”

Section: Clinical Studies -Observationalmentioning

confidence: 99%

Immunosuppression and HCV recurrence after liver transplantation

Samonakis¹,

Germani²,

Burroughs³

2012

Journal of Hepatology

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HCV related liver disease is the most common indication for liver transplantation. Recurrence of HCV infection is universal and has a substantial impact on patient and graft survival. Immunosuppression is a major factor responsible for the accelerated recurrence and compressed natural history of recurrent HCV infection. Accumulating experience has provided data to support certain strategies for immunosuppressive regimens. From the available evidence, more severe recurrence results from repeated bolus corticosteroid therapy and anti-lymphocyte antibodies used to treat rejection. Low dose and slow tapering of steroids are better than high dose maintenance and/or rapid tapering. Recent meta-analyses favour steroid-free regimens but these are complicated to interpret as the absence of steroids may simply represent less immunopotency. There is no difference in HCV recurrence between tacrolimus and cyclosporine regimens, but tacrolimus increases graft and patient survival in HCV transplanted patients. There may be a beneficial effect of maintenance azathioprine given for 6 months or longer. There is no conclusive evidence for benefit of mycophenolate and interleukin-2 receptor blockers. Few data are available for mTOR inhibitors. Better evidence is needed to establish the optimal immunosuppressive regimen for HCV recipients and more randomized trials should be performed.

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The Use of Cyclosporine for Recurrent Hepatitis C After Liver Transplant: A Randomized Pilot Study

Cited by 52 publications

References 29 publications

Management of Hepatitis C Before and After Liver Transplantation in the Era of Rapidly Evolving Therapeutic Advances

Management of Hepatitis C Before and After Liver Transplantation in the Era of Rapidly Evolving Therapeutic Advances

Strategies to reduce hepatitis C virus recurrence after liver transplantation

Immunosuppression and HCV recurrence after liver transplantation

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