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) Ͼ45 IU/L; and 3) a liver biopsy showing chronic hepatitis without rejection in the previous 2 months. Patients received PEG-IFN (1.5 g/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 Ͻ 0.05) but not in nonresponder patients. Fibrosis did not change significantly in either group. SVR was significantly associated with low ␥-glutamyltransferase GGT (P ϭ 0.04) and HCV-RNA levels (P ϭ 0.03), a virological response at 12 weeks (P ϭ 0.002) and patient's compliance (P ϭ 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 Ten (21%) patients were withdrawn prematurely due to adverse effects.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.

Recurrent hepatitis C after liver transplantation: On-treatment prediction of response to peginterferon/ribavirin therapy

“…It has been demonstrated by multivariable analysis that EVR is significantly associated with SVR in the transplant setting. 9,10 In our study, EVR had a very high NPV to identify those who will not achieve SVR. However, it was apparent that a number of patients who reach EVR after 12 weeks of treatment will not get SVR, suggesting its limitation as a positive predictive factor.…”

“…9,10,12 While still suboptimal, these rates of SVR are somewhat higher than those observed with the standard interferon and RBV combination therapy (ϳ20%) or those with pegylated interferon monotherapy (ϳ10%). [5][6][7] The lower rate of SVR compared to nontransplant HCV patients can be attributed to several factors including differences in the HCV dynamics between the immunocompetent and immunocompromised hosts, 20,21 higher prevalence of insulin resistance in LT recipients, and lower tolerability of PEG/RBV.…”

“…To date, there have been 10 published studies that enrolled greater than 20 patients each to evaluate the efficacy and safety of PEG/RBV combination therapy in LT patients with reported SVR rates ranging between 31% and 45%. 9,10,13,18,19 Several factors have been identified and shown to be associated with a higher SVR rates in patients with chronic HCV outside the transplant setting, including low body mass index, 19 14 were identified as predictors of SVR in non-LT chronic HCV patients but have not been adequately assessed in LT patients. Identification of predictors of treatment outcome in HCV patients has direct clinical utility and it allows for better selection of candidates and optimizes the outcome of therapy while minimizing the treatment length and side effects associated with antiviral medications.…”

Mission poorly accomplished: The protective role of natural killer cells in recurrent hepatitis C after liver transplantation

“…At best, viral eradication is achieved in only 20%-35% of patients treated with the standard therapeutic regimen of pegylated interferon and ribavirin. 1,2 The development of rapidly progressive recurrent hepatitis after OLT in HCV patients is associated with histologic injury and fibrosis. As many as 20% of HCV patients develop cirrhosis within the first 5 years after OLT, and the overall survival of this cohort of patients is substantially compromised compared to that of patients transplanted for indications other than HCV.…”

Long-term histological effects of preemptive antiviral therapy in liver transplant recipients with hepatitis C virus infection

“…2,3 Unfortunately, SVR rates are less than desired, with only 23% to 45% of treated patients achieving this endpoint. [4][5][6][7][8] Initiation of treatment in the early posttransplant period has been proposed as a potentially more effective means of preventing or ameliorating recurrent HCV disease. With preemptive therapy, as typically defined, antiviral therapy is usually begun within the first 2 to 8 weeks post-transplantation before there is histological evidence of recurrent disease.…”