Clinical and histological efficacy of pegylated interferon and ribavirin therapy of recurrent hepatitis C after liver transplantation.
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 Ten (21%) patients were withdrawn prematurely due to adverse effects.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: After liver transplantation (LT) for HCV-related cirrhosis, recurrence of HCV infection is universal and the risk of progression to cirrhosis is high. The modalities and efficacy of antiviral therapy in this indication are still controversial. We present here the results of a pilot study of a 12-month combination therapy by pegylated alfa 2b-interferon (PEG-IFN) and ribavirin in 20 patients. Twenty patients entered the study (13 male and 7 female, median age 53.8 years). In 80% of patients, HCV infection was of genotype 1. The delay between LT and antiviral therapy was 28 months. The doses were progressively increased from 0.5 to 1 micro g/kg/week for PEG-IFN and from 400 to 1000-1200 mg/d for ribavirin. Follow-up was based on biochemical (ALT), virological (HCV-RNA) and histological (liver biopsy) examinations. Four patients (20%) were withdrawn due to adverse effects. In 6 patients the dose of PEG-IFN had to be reduced to 0.5 micro g/kg/week. A reduction in the dose of ribavirin in 13/16 cases was due to the onset of anemia. Histological evidence of mild acute rejection increased the immunosuppressive regimen in 5/20 patients. At the end of the treatment, 75% of the patients had a biochemical response and 55% a virological response. The mean METAVIR score, according to activity and fibrosis, was A1.8 F2.2 before treatment and A0.3 F1.6 at the end of treatment. In 9/20 patients, virological response persisted 6 months after the end of the treatment. Our results suggest that combination therapy by PEG-IFN and ribavirin may be well tolerated and beneficial during recurrent hepatitis C in liver transplant recipients.Journal of Hepatology 05/2004; 40(4):669-74. · 9.86 Impact Factor
- Hepatology 04/2005; 41(3):436-8. · 12.00 Impact Factor
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ABSTRACT: The aim of this open trial was to assess the efficacy and the safety of interferon (IFN) alfa therapy in liver transplant recipients with chronic active hepatitis caused by hepatitis C virus. In July 1991, among 447 liver recipients regularly observed at our institution, 46 had developed HCV-related chronic active hepatitis defined by piece meal necrosis. Fourteen of these 46 patients received IFN alfa 3 mIU three times weekly for a planned duration of 6 months and were compared to the 32 untreated patients. Genotyping and quantification of viremia were performed using type-specific amplification and branched DNA assay. Histological follow-up was available in all patients and routinely before and after IFN therapy. Treated and untreated patients did not differ regarding gender, age, length of follow-up, maximum histological score, and genotypes (41 of 46 were of type 1b). Induction of chronic rejection was observed in 5 of 14 treated patients leading to retransplantation in 3. In contrast, chronic rejection occurred in 1 of 32 untreated patients (P < .005) during the posttransplantation follow-up. Among the 9 treated patients without rejection, a decrease of transaminases or of HCV RNA levels of more than 50% were observed in 8 and 4, respectively; 2 patients had a complete response, and 1 did not relapse after discontinuation of IFN. Histological improvement occurred in 2 of the treated patients and in none of the untreated patients. IFN therapy in liver transplant recipients has poor antiviral effect and can induce chronic rejection. Its use in this setting should be cautious.Hepatology 11/1995; 22(4 Pt 1):1084-9. · 12.00 Impact Factor