Treatment of recurrent HCV infection following liver transplantation: Results of a multicenter, randomized, versus placebo, trial of ribavirin alone as maintenance therapy after one year of PegIFNα-2a plus ribavirin
Hôpital Saint-Antoine, Paris, France. Journal of Hepatology
(Impact Factor: 11.34).
05/2012; 57(3):564-71. DOI: 10.1016/j.jhep.2012.04.022
We aimed at determining the effect of maintenance therapy with ribavirin alone, after a year of combined peginterferon-alfa 2a (PegIFNα-2a) and ribavirin therapy, on viral response and liver histology after liver transplantation (LT).
Hundred and one patients with recurrent HCV and a minimum of stage 1 fibrosis (METAVIR scoring), 1-5years after LT, were enrolled. PegIFNα-2a and ribavirin were initiated at 90 μg/wk and 600 mg/d, respectively, then increased or adjusted as a function of tolerance. At 12 months, combination therapy was discontinued and patients were randomized to ribavirin or placebo for a further 12 months. Growth factor use was permitted.
At 18 months, a sustained virological response (SVR) was obtained in 47.9% of patients in Per Protocol (PP) analysis, and was higher in patients with genotype 2 or 3 than in patients with genotype 1 or 4, in patients with genotypes 1+4 receiving ciclosporine than in those receiving tacrolimus, in patients with worse renal function, in those having received EPO, in patients with lower weight, and in those with lower viral load at 3 months. Using logistic regression, only the early viral response, recipient weight and renal function were independently associated with better SVR. SVR, viral load, activity, and fibrosis scores were similar, at M18 and M30, in patients randomized to ribavirin, or to placebo.
A PP SVR was achieved in 47.9% of patients with established recurrent hepatitis C after LT. Maintenance therapy with ribavirin alone does not improve the virological response or the histological parameters.
Available from: onlinelibrary.wiley.com
[Show abstract] [Hide abstract]
ABSTRACT: Hepatitis C virus (HCV) infection is one of the leading causes of end-stage liver disease and the main indication for liver transplantation (LT) in most countries. All patients who undergo LT with detectable serum HCV RNA experience graft reinfection. Between 20 and 30% of patients develop cirrhosis within 5 years post-LT. The outcome of transplant patients with cirrhosis on the graft is severe, with a rate of decompensation at 1 year of around 40%. To date, retransplantation is the only option for patients who develop decompensation. Until 2011, standard antiviral therapy, using pegylated interferon (PEG-IFN) and ribavirin (RBV), was the only effective therapy. Obtaining a sustained virological response (SVR) in the setting of LT greatly improves overall and graft survival, but this only concerns 30% of transplanted patients. Direct-acting antivirals (DAA) such as protease inhibitors, polymerase or other non-structural proteins inhibitors represent a new era in HCV-associated liver disease. Although their use in the field of liver transplantation seems to be essential, there are some limitations due to safety and tolerance. One limitation is the potential interaction with calcineurin inhibitors. We describe the preliminary results of triple therapy with boceprevir or telaprevir in terms of efficacy and safety in liver transplant recipients.
[Show abstract] [Hide abstract]
ABSTRACT: Hepatitis B immune globulin-free therapeutic regimens with a nucleos(t)ide analogue (NUC) or NUC combinations after liver transplantation (LT) are currently being investigated for their efficacy and safety as HBV re-infection prophylaxis in clinical studies. Recurrence rates differ among these studies as most of them are limited by a non-randomised study design, small sample size, lack of long-term data and varying time intervals for the switch from combined to purely virostatic prophylaxis. Post-transplant pre-emptive antiviral therapy with pegylated IFN and ribavirin is associated with low sustained virological response rates and was found to have no advantage over treatment of manifest HCV re-infection. Safety and efficacy of triple antiviral therapy including boceprevir or telaprevir in patients with manifest HCV re-infection are currently under investigation in clinical trials. Relevant drug interactions have been shown to occur during calcineurin inhibitor (CNI) and concomitant triple antiviral therapy, which vary with type of CNI and choice of HCV protease inhibitor. Newer direct-acting antivirals with lower or minimal toxicity, when used in combination with immunosuppressives, are worthy of further study in LT patients. This review focuses on hot topics in the management of hepatitis B and C patients before and after LT and offers a critical summarised selection of the corresponding relevant studies published in the current literature or presented at recent liver congresses. Copyright © 2012 John Wiley & Sons, Ltd.
[Show abstract] [Hide abstract]
ABSTRACT: The goal of hepatitis C virus (HCV) treatment in liver transplant (LT) recipients is to prevent graft loss and liver-related complications. Currently, the primary approach to the management of transplant recipients with HCV has been to treat after transplantation (Table 4.1). Antiviral therapy can be undertaken early, within the first 6 months post-LT, when recurrent viremia is documented, but prior to the presence of histologic criteria for treatment. This is often termed preemptive therapy. More commonly, treatment with antiviral therapy is reserved for those with recurrent and progressive histologic disease. Experts recommend treatment for patients with moderate to severe necroinflammatory activity or mild to moderate fibrosis (F2 or greater). Peginterferon and ribavirin has been the mainstay of posttransplant therapy for the past 15 years. With the recent approval of the first direct-acting antiviral (DAA) drugs-NS3/4A protease inhibitors-the standard of care for patients with genotype 1 HCV infection has changed to a triple drug regimen of peg-IFN, RBV, and either telaprevir or boceprevir. Since the majority of transplant recipients with HCV are infected with HCV genotype 1, this offers a significant opportunity to improve outcomes in these patients. Although, triple therapy is not approved for use in transplant recipients, off-label use is occurring due to significant need for more efficacious therapies in patients with progressive or severe recurrent disease. However, significant challenges including a higher risk of adverse events and more drug-drug interactions have been identified in early reports. In the future, DAA drugs with improved tolerability and less drug-drug interactions may allow greater ease of use, better tolerability, and higher rates of viral clearance. © 2014 Springer Science+Business Media New York. All rights are reserved.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.