Chronic Hepatitis C Clinical Trial
Official title:
Retreatment of Dialysis Patients With Chronic Hepatitis C With Pegylated Interferon Alfa-2a Plus Low Dose Ribavirin Who Fail Interferon Alfa or Pegylated Interferon Alfa Monotherapy - a Pilot Study
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.
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.
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Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
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