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Efficacy of the retreatment of hepatitis C virus infections after liver transplantation: Role of an aggressive approach

Authors

  • Marina Berenguer,

    Corresponding author
    1. Liver Transplantation and Hepatology Unit, La Fe Hospital, Valencia, Spain
    2. Network Center for Biomedical Research in Hepatic and Digestive Diseases, Valencia, Spain
    3. Faculty of Medicine, University of Valencia, Valencia, Spain
    • Department of Medicina Digestiva, La Fe Hospital, Torre F-5, C/Bulevar sn, Valencia 46026, Spain
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  • Bruno Roche,

    1. Hepatobiliary Center (National Institute of Health and Medical Research U785), Paul Brousse Hospital, University Paris Sud, Villejuif, France
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  • Victoria Aguilera,

    1. Liver Transplantation and Hepatology Unit, La Fe Hospital, Valencia, Spain
    2. Network Center for Biomedical Research in Hepatic and Digestive Diseases, Valencia, Spain
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  • Jean-Charles Duclos-Vallée,

    1. Hepatobiliary Center (National Institute of Health and Medical Research U785), Paul Brousse Hospital, University Paris Sud, Villejuif, France
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  • Laia Navarro,

    1. Network Center for Biomedical Research in Hepatic and Digestive Diseases, Valencia, Spain
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  • Angel Rubín,

    1. Liver Transplantation and Hepatology Unit, La Fe Hospital, Valencia, Spain
    2. Network Center for Biomedical Research in Hepatic and Digestive Diseases, Valencia, Spain
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  • Jose-Antonio Pons,

    1. Network Center for Biomedical Research in Hepatic and Digestive Diseases, Valencia, Spain
    2. Liver Transplantation and Hepatology Unit, Virgen de la Arrixaca Hospital, Murcia, Spain
    3. Faculty of Medicine, University of Murcia, Murcia, Spain
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  • Manuel de la Mata,

    1. Network Center for Biomedical Research in Hepatic and Digestive Diseases, Valencia, Spain
    2. Liver Transplantation and Hepatology Unit, Princesa Sofia Hospital, Córdoba, Spain
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  • Martín Prieto,

    1. Liver Transplantation and Hepatology Unit, La Fe Hospital, Valencia, Spain
    2. Network Center for Biomedical Research in Hepatic and Digestive Diseases, Valencia, Spain
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  • Didier Samuel

    1. Hepatobiliary Center (National Institute of Health and Medical Research U785), Paul Brousse Hospital, University Paris Sud, Villejuif, France
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  • This work was supported in part by the Spanish Ministry of Science through the Health Research Fund of the Carlos III Institute of Health (PS09/01707 and Network Center for Biomedical Research in Hepatic and Digestive Diseases).

Abstract

A sustained virological response (SVR) is achieved by 30% of naive liver transplantation (LT) recipients treated with pegylated interferon (PEG-IFN) and ribavirin (RBV). Almost no data are available about retreatment. The aim of this study was to assess the efficacy, tolerability, and SVR predictors of retreatment. Data were collected from 4 centers on the retreatment of prior nonresponders to standard therapy or PEG-IFN (with or without RBV) and relapsers. Seventy-nine of 301 treatment-experienced LT patients (26%), who had a median age of 59 years (range = 35-77 years) and were mostly male (72%) and infected with genotype 1 (87%), were retreated with PEG-IFN and RBV at a median of 6.9 years after LT. During the first course of therapy, 35% were treated with interferon, 49% received tacrolimus, 52% received steroids, and 49.5% were relapsers. Retreatment was started at a median of 1.9 years (range = 45 days to 8.2 years) after the end of the first course. The proportion of patients with cirrhosis increased from 10% to 37% (P < 0.001). In addition, in retreated patients, full initial RBV doses (P = 0.03), growth factors [erythropoietin (P < 0.001) and granulocyte colony-stimulating factor (P = 0.048)], and transfusions (P = 0.03) were used more frequently, and the treatment duration was longer (P = 0.03). An end-of-treatment response was achieved in 61%, whereas SVR, which was associated with improved survival, occurred in 28 (35%). The variables predicting SVR were age (P = 0.04), disease severity [fibrosis (50% with F0-F2 versus 26% with F3-4), P = 0.03; bilirubin, P = 0.006; platelet count, P = 0.03], adherence, and viral kinetics. None of the patients without an early virological response achieved SVR. There was a trend of prior relapsers achieving higher SVR rates than prior nonresponders. In conclusion, SVR, which was achieved by approximately one-third of the retreated patients, can be predicted with the same variables used for naive LT recipients (age, disease severity, adherence, and viral kinetics) and is associated with enhanced survival. Liver Transpl 19:69–77, 2013. © 2012 AASLD.

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