Preemptive Therapy for Hepatitis C Virus after Living-Donor Liver Transplantation

Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Transplantation (Impact Factor: 3.83). 12/2004; 78(9):1308-11. DOI: 10.1097/01.TP.0000142677.12473.E5
Source: PubMed


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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    • "Thereafter, the dosage was gradually increased as tolerated. Finally, pegylated-interferon alpha-2b 1.5 µg/kg/week and RBV 800 mg/day were administered, depending on patient compliance [17], [18]. "
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    ABSTRACT: Single nucleotide polymorphisms of interleukin-28B (IL28B) rs8099917 are reported to be associated with virologic clearance in interferon-and ribavirin -based treatment for hepatitis C virus (HCV)-infected patients. We examined virologic response in accordance with IL28B polymorphisms in our living donor liver transplantation series under a preemptive interferon and RBV treatment approach. Adequate DNA samples from both the recipient and donor for the study of single nucleotide polymorphisms of IL28B were available from 96 cases and were the subjects of the present study. Various clinical factors related with virologic response including early virologic response (EVR) and sustained virologic response (SVR) were examined. Totally 51% presented with EVR and 44% achieved SVR. Presence of the major allele (TT) in either the recipient or the donor corresponded to SVR of 53% and 48%. Presence of the minor allele (TG or GG) corresponded to SVR of 26% and 32%. Multivariate analysis revealed that genotype of HCV or EVR, but not IL28B polymorphisms in either the recipient or donor, was an independent factor for achieving SVR. When virologic response to treatment was incorporated into analysis, the impact of IL28B polymorphism on virological clearance remained relative to other factors and was not significantly independent.
    Full-text · Article · Mar 2014 · PLoS ONE
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    • "None of the patients developed graft rejection, and normal histology was also noted in patients with SVR after a median followup of 52 months. However, higher than 26% of graft rejection was noted in another study using IFN and RBV combination therapy for more than 12 months [65]. Moreover, four other studies using different regiments, two IFN monotherapy and two pegylated—IFN monotherapy, showed a poor effect of less than 20% of SVR and a higher rate of treatment discontinuation and graft rejection [66–69]. "
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    ABSTRACT: Hepatitis C virus (HCV) is a small-enveloped RNA virus belonging to the Flaviviridae family. Since first identified in 1989, HCV has been estimated to infect 170 million people worldwide. Mostly chronic hepatitis C virus has a uniform natural history, from liver cirrhosis to the development of hepatocellular carcinoma. The current therapy for HCV infection consists of a combination of Pegylated interferon and ribavirin. On the other hand, HCV-related liver disease is also the leading indication for liver transplantation. However, posttransplant HCV re-infection of the graft has been reported to be universal. Furthermore, the graft after HCV re-infection often results in accelerated progression to liver failure. In addition, treatment of recurrent HCV infection after liver transplantation is often compromised by enhanced adverse effects and limited efficacy of interferon-based therapies. Taken together, poor outcome after HCV re-infection, regardless of grafts or recipients, poses a major issue for the hepatologists and transplant surgeons. The aim of this paper is to review several specific aspects regarding HCV re-infection after transplant: risk factors, current therapeutics for HCV in different stages of liver transplantation, cellular function of HCV proteins, and molecular mechanisms of HCV entry. Hopefully, this paper will inspire new strategies and novel inhibitors against recurrent HCV infection after liver transplantation and greatly improve its overall outcome.
    Full-text · Article · Apr 2013 · Clinical and Developmental Immunology
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    • "Prevention of graft reinfection may be achieved through eradication of the virus by use of antiviral therapy before transplantation and use of hepatitis C immunoglobulins [4] [5] [6] [7]. Additionally, after transplantation, antiviral therapy can be used either preemptively to prevent allograft injury in the first weeks [8] [9] [10] or, more commonly, to prevent progression to cirrhosis in patients with recurrent hepatitis. Management of chronic hepatitis C in liver transplant recipients with recurrent hepatitis C has improved significantly during the past decade. "
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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.
    Full-text · Article · Sep 2008 · Journal of Hepatology
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