Retreatment of Dialysis Patients With Chronic Hepatitis C With Pegylated Interferon Alfa-2a Plus Low Dose Ribavirin
Condition: Chronic Hepatitis C; Hemodialysis
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic
Study type: Interventional
Phase: Phase 4

Summary: 
      Chronic hepatitis C virus (HCV) infection is common in dialysis patients. Interferon
      (IFN)-based treatment for chronic hepatitis C has been the mainstay therapy in
      immunocompetent patients. Two meta-analyses evaluating the efficacy and safety of
      conventional IFN alfa monotherapy showed that the sustained virologic response (SVR) rates
      were 37% and 33%, respectively; and the corresponding dropout rates were 17% and 29.6%,
      respectively. The efficacy and safety of pegylated IFN alfa-2a and 2b in treating dialysis
      patients showed conflicting results, with a more favorable outcome of patients treated with
      pegylated IFN alfa-2a (135-180 μg/week: SVR 33-75%, well tolerated) than those treated with
      pegylated IFN alfa-2b (0.5-1.0 μg/week: SVR 12.5%, poorly tolerated), Currently, IFN-based
      therapy to treatment HCV infection should be initiated in dialysis stages, because the use of
      IFN in RT patients harbors high risks of acute graft rejection,and have low response rates
      under the concomitant use of immunosuppressive agents.

      Ribavirin, which has been used in combination with IFN to treat chronic hepatitis C in the
      general patients and achieve a higher SVR rate than IFN monotherapy, is considered
      contraindicated in dialysis patients with chronic hepatitis C due to the risk of severe
      hemolytic anemia. However, some pilot studies evaluating combined conventional IFN alfa plus
      low dose ribavirin (170-300 mg/day) showed SVR rates of 17%-66% after 24-48 weeks of
      treatment.In addition, a recent study including 6 patients with combination of pegylated IFN
      alfa plus low dose ribavirin also showed a SVR rate of 50%.

      Although dialysis patients have a higher SVR rate to conventional IFN or pegylated IFN
      monotherapy than patients with normal renal function for HCV therapy. More than half of these
      patients are relapsers or non-responders to IFN monotherapy. Retreatment of HCV-patients with
      normal renal function by combined pegylated IFN alfa plus ribavirin who fail to response to
      IFN monotherapy has achieved a SVR rate of 28%. Based on the long-term favorable outcome in
      dialysis patients who eradicate HCV, the aim of the study is to evaluate the efficacy and
      safety of retreatment by pegylated IFN alfa-2a plus low dose ribavirin in dialysis patients
      who fail to achieve HCV eradication by conventional or pegylated IFN alfa.
    

Detailed description: 
      Chronic hepatitis C virus (HCV) infection is common in dialysis patients, with the reported
      prevalence varying from 3% to 80% worldwide.(1-3) Although these patients usually have mild
      symptoms and moderate elevation of alanine transaminase levels, recent international
      collaborative survey and prospective studies found that anti-HCV seropositivity and positive
      HCV RNA were risk factors for mortality and hepatocellular carcinoma (HCC).(4-7) Furthermore,
      progressive hepatic fibrosis, poor patient and graft survival were observer in dialysis
      patients with HCV infection who undergo renal transplantation (RT), suggesting
      immunosuppression following RT may worsen the course of hepatic fibrosis and renal graft
      function.(8-13) These lines of evidence indicate that HCV infection in the dialysis
      population is an important issue to be tackled.

      Interferon (IFN)-based treatment for chronic hepatitis C has been the mainstay therapy in
      immunocompetent patients. In dialysis patients, treatment with conventional or pegylated
      interferon has also received much attention recently. Two meta-analyses evaluating the
      efficacy and safety of conventional IFN alfa monotherapy showed that the sustained virologic
      response (SVR) rates were 37% and 33%, respectively; and the corresponding dropout rates were
      17% and 29.6%, respectively.(14,15) The efficacy and safety of pegylated IFN alfa-2a and 2b
      in treating dialysis patients showed conflicting results, with a more favorable outcome of
      patients treated with pegylated IFN alfa-2a (135-180 μg/week: SVR 33-75%, well tolerated)
      than those treated with pegylated IFN alfa-2b (0.5-1.0 μg/week: SVR 12.5%, poorly
      tolerated),(16-21) which may result from different pharmacokinetic profiles between these two
      pegylated IFNs. Currently, IFN-based therapy to treatment HCV infection should be initiated
      in dialysis stages, because the use of IFN in RT patients harbors high risks of acute graft
      rejection,(22,23) and have low response rates under the concomitant use of immunosuppressive
      agents.(24,25) Ribavirin, which has been used in combination with IFN to treat chronic
      hepatitis C in the general patients and achieve a higher SVR rate than IFN monotherapy, is
      considered contraindicated in dialysis patients with chronic hepatitis C due to the risk of
      severe hemolytic anemia. However, some pilot studies evaluating combined conventional IFN
      alfa plus low dose ribavirin (170-300 mg/day) showed SVR rates of 17%-66% after 24-48 weeks
      of treatment.(26-28) In addition, a recent study including 6 patients with combination of
      pegylated IFN alfa plus low dose ribavirin also showed a SVR rate of 50%.(29) Although
      dialysis patients have a higher SVR rate to conventional IFN or pegylated IFN monotherapy
      than patients with normal renal function for HCV therapy. More than half of these patients
      are relapsers or non-responders to IFN monotherapy. Retreatment of HCV-patients with normal
      renal function by combined pegylated IFN alfa plus ribavirin who fail to response to IFN
      monotherapy has achieved a SVR rate of 28%.(30) Based on the long-term favorable outcome in
      dialysis patients who eradicate HCV, the aim of the study is to evaluate the efficacy and
      safety of retreatment by pegylated IFN alfa-2a plus low dose ribavirin in dialysis patients
      who fail to achieve HCV eradication by conventional or pegylated IFN alfa.
    

Intervention name(s): Pegylated interferon alfa-2a and ribavirin; Pegylated interferon alfa-2a and ribavirin
Intervention type(s): Drug; Drug
Intervention description(s): Pegylated interferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 135 ug/week plus ribavirin (Copegus, F. Hoffman-LaRoche) 200 mg/day for 48 weeks; Pegylated interferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 135 ug/week plus ribavirin (Copegus, F. Hoffman-LaRoche) 200 mg/day for 24 weeks
Intervention MeSH terms: Interferons; Ribavirin; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2a
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Chronic hepatitis C; hemodialysis; interferon; ribavirin