Clinical and histological efficacy of pegylated interferon and ribavirin therapy of recurrent hepatitis C after liver transplantation.

Gastroenterology Department, Hospital Universitario "12 de Octubre," Madrid, Spain.
Liver Transplantation (Impact Factor: 3.94). 12/2006; 12(12):1805-12. DOI: 10.1002/lt.20883
Source: PubMed

ABSTRACT Treatment of recurrent hepatitis C in liver transplant is controversial. The aim of our study was to evaluate the clinical and histological efficacy of pegylated interferon alpha 2b (PEG-IFN) and ribavirin therapy of recurrent hepatitis C after liver transplantation (LT). We prospectively included 47 liver transplant patients with: 1) a positive test for hepatitis C virus (HCV)-ribonucleic acid (RNA) in serum; 2) alanine aminotransferase (ALT) >45 UI/mL; and 3) a liver biopsy showing chronic hepatitis without rejection in the previous 2 months. Patients received PEG-IFN (1.5 microg/kg/week) and ribavirin (800-1,000 mg/day) for 12 months. Follow-up was based on biochemical (ALT), virological (RNA-HCV), and histological (liver biopsy) examinations. Follow-up lasted a minimum of 6 months after the end of antiviral therapy. Sustained virological response (SVR) was achieved in 23% of the patients. A total of 33 (70%) patients had normalized ALT levels at the end of therapy. Inflammatory portal and lobular score declined significantly in patients with SVR (P < 0.05) but not in nonresponder patients. Fibrosis did not change significantly in either group. SVR was significantly associated with low gamma-glutamyltransferase GGT (P = 0.04) and HCV-RNA levels (P = 0.03), a virological response at 12 weeks (P = 0.002) and patient's compliance (P = 0.04). Ten (21%) patients were withdrawn prematurely due to adverse effects. In conclusion, Therapy with PEG-IFN and ribavirin achieved SVR and a significant histological improvement in 23% of liver transplant recipients with chronic hepatitis C. Toxicity is an important drawback of this therapy.

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    ABSTRACT: Chronic infection with the hepatitis C virus (HCV) represents one of the major causes for end-stage liver disease worldwide. Although liver transplantation offers an effective treatment, HCV reinfection of the transplanted graft is a critical and almost inevitable complication with major influence on graft- and patient survival. Pre-transplant antiviral therapy in advanced liver disease is limited by poor tolerance and only applicable to mildly decompensated patients but was able to show promising results in patients reaching negative viral load when undergoing transplantation. Prophylactic therapy with HCV antibodies during the anhepatic phase has not been shown to be effective in studies to date. Antiviral therapy after transplantation but before evidence of reinfection, so called pre-emptive treatment, is limited by frequent complications and a high rate of side effects. The mainstay of management represents directed antiviral therapy after evidence of recurrence of chronic Hepatitis C. With a combination therapy of pegylated interferon and ribavirin, sustained virologic response rates of 25-45% are achieved. However, tolerability is often poor, and the need of dose reduction is frequent. To date, there is no general consensus on modality, timing and dosing of antiviral treatment of HCV in patients with advanced liver disease and after liver transplantation. More randomised, controlled trials are needed. Moreover, upcoming new treatment approaches, e.g. specifically targeted antiviral therapy for hepatitis C (STAT-C) with HCV-specific polymerase and protease inhibitors, may represent a therapeutic alternative.
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    Liver Transplantation 02/2008; 14(1):4-6. · 3.94 Impact Factor
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    ABSTRACT: INTRODUCTION: Severity of recurrent hepatitis C virus (HCV) infection in liver transplant recipients (LTR) is variable and the influence of different factors, including the administration of antiviral therapy in the long-term outcome is controversial. METHODS: We analyzed the outcome of a cohort of HCV-infected LTR who were transplanted in our institution. Patients were divided into 2 groups (severe and non-severe HCV disease) depending on the presence of a fibrosis score of F ≥2 in the Scheuer index and/or fibrosing cholestasic hepatitis (FCH) in a graft biopsy. Risk factors were studied using logistic regression analysis. Survival of patients was estimated using Kaplan-Meier plots. A total of 146 patients were followed for a mean of 58 months. RESULTS: Fifty-six (34%) patients developed severe HCV disease and showed shorter survival (P < 0.024). Donor age (odds ratio [OR]: 1.04; 95% confidence interval [CI]: 1.02-1.06) and pre-transplant viral load (VL) >10(6) UI/mL (OR: 3.5; 95% CI: 1.42-10.61) were the only factors associated with severe HCV infection. Over-immunosuppression (OR: 2.3; 95% CI: 1.2-4.41) was specifically associated with the development of FCH. Overall, patient survival in recipients who received a full course of anti-HCV therapy was higher than in patients who did not complete antiviral therapy (P = 0.004) or received no treatment (P = 0.007). Patients with non-severe HCV infection have a higher probability of receiving a full course of antiviral therapy (P = 0.033). CONCLUSION: In conclusion, donor age, pre-transplant VL, and over-immunosuppression were associated with the long-term development of severe HCV recurrence in liver grafts. Administration of a full course of antiviral therapy was associated with better survival.
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