Preemptive therapy for hepatitis C virus after living-donor liver transplantation.
ABSTRACT Living-donor liver transplantation (LDLT) is important for patients with end-stage viral hepatitis because of the cadaveric organ shortage. Preliminary results, however, indicate that LDLT might be disadvantageous for patients positive for hepatitis C virus (HCV).
The subjects were 23 patients who underwent LDLT for HCV cirrhosis. All the patients preemptively received antiviral therapy consisting of interferon-alfa2b and ribavirin, which was started approximately 1 month after the operation. The therapy continued for 12 months after the first negative HCV RNA test. The patients were then observed without the therapy for 6 months (group 1). The therapy was continued for at least 12 months even when the HCV RNA test remained positive (group 2). The subjects were removed from the protocol if they could not continue the therapy for 12 months because of adverse effects or could not start the therapy because of early death.
Eight patients were removed from the protocol. Nine patients were assigned to group 1 and the other six to group 2. The sustained virologic response ratio was 39% (9 of 23). There was a significant difference between the groups in the histologic activity score 1 year after the therapy. The cumulated 3-year survival of the HCV-positive patients was 85%, which was comparable with that of patients negative for HCV (n=93 [90%]).
The present preemptive antiviral protocol after LDLT is safe and might warrant a controlled study for confirming its benefit on graft survival.
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ABSTRACT: The aim of our study was to conduct a systematic review of studies evaluating antiviral therapy with pegylated interferon (PEG-IFN) alfa in combination with ribavirin for the management of recurrent hepatitis C after liver transplantation. Data sources included electronic databases and a manual search. Studies evaluating the efficacy and tolerability of PEG-IFN alfa with ribavirin in patients with recurrent hepatitis C were selected for inclusion. The information extracted from each of the selected publications included study design details, patient characteristics, treatment regimens and efficacy and tolerability end points. Nineteen studies including 611 patients were identified. PEG-IFN alfa-2b was used in 16 studies. The mean rate of SVR was 30.2% (range, 8-50%). Dose reduction and discontinuation of treatment were common in these studies (73% and 27.6%, respectively). The lack of an early virologic response (EVR) at 3 months of therapy was the most frequently described predictive factor of nonresponse. Treatment discontinuation and dose reductions due to adverse events were frequent and possibly represent important obstacles to attainment of SVR. EVR at 3 months of treatment should be considered an important predictor of treatment outcome.Journal of Hepatology 09/2008; 49(2):274-87. DOI:10.1016/j.jhep.2008.05.002 · 10.40 Impact Factor
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ABSTRACT: Background/Aims: The impact of pegylated-interferon (PEG-IFN) alpha-2b on liver regeneration has not yet been elucidated. Methodology: Rats were divided into the following four groups: 70% hepatectomy (Hx); 70% Hx+PEG-IFN; 90% Hx and 90% Hx+PEG-IFN group (n=6 each). Rats were pretreated with subcutaneous of PEG-IFN alpha-2b (1.5 mu g/kg) administration 24 hours before Fix. Samples were taken 24, 48 and 72 hours after Fix and the following parameters were investigated: blood analysis (AST, WBC, PLT); liver weight to body weight ratio (Lw/Bw ratio); survival and PCNA labeling index (LI). Results: In the 90% Hx model, there was no significant difference between the Hx+PEG-IFN group and the Hx alone group in blood analysis; AST after postoperative 24 hours (2511 vs. 2466IU/L), WBC (1200 vs. 1290) and PLT (107 vs. 111 x 10(4)/mm(3)), in Lw/Bw ratio at postoperative 0, 24, 48, 72 hours, respectively (0.38, 0.60, 1.14, 1.69 vs. 0.37, 0.64, 1.12, 1.63), in postoperative survival (40% vs. 45%), and in PCNA LI at postoperative 0, 24, 48, 72 hours, respectively (10.4%, 16.8%, 14.6%, 12.8% vs. 10.0%, 17.1%, 15.6%, 13.7%). In the 70% Hx model, there was no significant difference between the Hx+PEG-IFN group and the Fix alone group for all parameters. Conclusions: Our data demonstrated that PEG-IFN alpha-2b did not affect liver regeneration and the early use of PEG-IFN alpha-2b would cause no problems after liver transplantation using partial grafts including living donor liver transplantation.Hepato-gastroenterology 10/2012; 59(119):2300-4. DOI:10.5754/hge10401 · 0.91 Impact Factor
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ABSTRACT: Hepatitis C virus (HCV) infection is one of the main indications for liver transplantation. Viral recurrence occurs in all patients with detectable serum HCV RNA at the time of transplantation leading to cirrhosis in 20-30 % of patients within 5 years. Viral eradication using antiviral therapy has been shown to improve patient and graft survival. Pegylated interferon (PEG-IFN) and ribavirin (RBV) antiviral therapy achieved SVR in around 30 % of transplant recipients. In the non-transplant setting, first generation NS3/4 protease inhibitors, boceprevir or telaprevir associated with PEG-IFN and RBV, has improved the SVR rates to 75 % in genotype 1 infected patients. However, tolerability and drug-drug interactions with calcineurin inhibitors are both limiting factors of their use in transplant recipients. In the non-transplant patients, using new direct-acting antiviral therapy has dramatically improved the efficacy of antiviral C therapy over recent years leading to SVR rates over 90 % in phase II and III clinical trials, without PEG-IFN and/or RBV. Preliminary results in transplant patients showed better efficacy, better tolerability and less drug-drug interactions.Hepatology International 03/2015; 9(2). DOI:10.1007/s12072-015-9621-5 · 2.47 Impact Factor