Interferon Alpha-2b Continuous LT Therapy Vs. Repeated Cycles for Hep C
Interferon Alpha-2b Continuous LT Therapy Vs. Repeated Cycles for Hep C
Background: Treatment options are limited for patients with hepatitis C virus who do not experience sustained viral eradication with pegylated interferon and ribavirin therapy.
Aim: To compare, in an open-label, randomized study, long-term continuous interferon alpha-2b treatment with repeated 24-week courses in patients with chronic hepatitis C virus that relapsed after prior interferon monotherapy.
Methods: A total of 499 patients received 24 weeks of interferon alpha-2b, 3 MIU administered 3 TIW. Responders (normal alanine aminotransferase and negative hepatitis C virus -RNA, n = 244) were then randomized to continuous interferon therapy (1, 2 or 3 MIU TIW depending on response) or cyclical therapy (3 MIU TIW for 24 weeks per relapse). Mean Knodell inflammation (I + II + III) and necrosis (IV) scores at baseline vs. year 2 were compared.
Results: Patients receiving continuous low-dose therapy vs. cycled therapy had larger reductions in inflammation (-3.9 vs. -3.1) and fibrosis (-0.49 vs. -0.24). Among both groups, the mean change was -3.4 for inflammation and -0.36 for fibrosis. Overall, 73% (95% CI: 67-79) of patients experienced reduced inflammation and 28% (95% CI: 22-34) had reduced fibrosis.
Conclusions: Our results suggest hepatitis C virus patients experiencing viral suppression during long-term maintenance therapy with interferon demonstrate histological improvement. Further prospective trials testing this hypothesis are in progress.
More than 170 million people worldwide are infected with hepatitis C virus (HCV). Chronic infection with HCV is the most common cause of cirrhosis and the most frequent indication for liver transplantation in the Western world. Current therapies with pegylated interferon and ribavirin result in sustained viral eradication in more than 50% of those who receive therapy, but many patients do not respond to or are unsuitable candidates to receive treatment. These patients, and particularly those with advanced fibrosis, are at a higher risk of disease progression. Yet, there are currently limited therapeutic options for them.
Until more effective therapies become available, one approach to managing these groups of individuals is to halt fibrosis progression. Such a therapy could be given long term, if it were relatively safe and well tolerated by patients. Interferon alpha has antifibrotic properties in vitro and in vivo. In a number of clinical studies, interferon alpha reversed or decreased the rate of fibrosis progression in patients with HCV infection. Evidence suggests that interferon alpha may, at least in the short term, halt disease progression. Furthermore, prospective studies are currently evaluating whether administering low-dose maintenance pegylated interferon prevents fibrotic disease progression in patients with hepatitis C and improves clinical end points.
We report the results of a study that was performed nearly 10 years ago evaluating the efficacy and safety of long-term continuous interferon alpha-2b treatment with repeated 24-week courses in chronic HCV patients who relapse after prior interferon monotherapy. The study was terminated prematurely because a more effective anti-viral combination therapy, interferon and ribavirin, had imminent approval in the United States. In view of the renewed interest in treatments that slow fibrosis progression, we analysed the results of this study and now report the findings.
Summary and Introduction
Summary
Background: Treatment options are limited for patients with hepatitis C virus who do not experience sustained viral eradication with pegylated interferon and ribavirin therapy.
Aim: To compare, in an open-label, randomized study, long-term continuous interferon alpha-2b treatment with repeated 24-week courses in patients with chronic hepatitis C virus that relapsed after prior interferon monotherapy.
Methods: A total of 499 patients received 24 weeks of interferon alpha-2b, 3 MIU administered 3 TIW. Responders (normal alanine aminotransferase and negative hepatitis C virus -RNA, n = 244) were then randomized to continuous interferon therapy (1, 2 or 3 MIU TIW depending on response) or cyclical therapy (3 MIU TIW for 24 weeks per relapse). Mean Knodell inflammation (I + II + III) and necrosis (IV) scores at baseline vs. year 2 were compared.
Results: Patients receiving continuous low-dose therapy vs. cycled therapy had larger reductions in inflammation (-3.9 vs. -3.1) and fibrosis (-0.49 vs. -0.24). Among both groups, the mean change was -3.4 for inflammation and -0.36 for fibrosis. Overall, 73% (95% CI: 67-79) of patients experienced reduced inflammation and 28% (95% CI: 22-34) had reduced fibrosis.
Conclusions: Our results suggest hepatitis C virus patients experiencing viral suppression during long-term maintenance therapy with interferon demonstrate histological improvement. Further prospective trials testing this hypothesis are in progress.
Introduction
More than 170 million people worldwide are infected with hepatitis C virus (HCV). Chronic infection with HCV is the most common cause of cirrhosis and the most frequent indication for liver transplantation in the Western world. Current therapies with pegylated interferon and ribavirin result in sustained viral eradication in more than 50% of those who receive therapy, but many patients do not respond to or are unsuitable candidates to receive treatment. These patients, and particularly those with advanced fibrosis, are at a higher risk of disease progression. Yet, there are currently limited therapeutic options for them.
Until more effective therapies become available, one approach to managing these groups of individuals is to halt fibrosis progression. Such a therapy could be given long term, if it were relatively safe and well tolerated by patients. Interferon alpha has antifibrotic properties in vitro and in vivo. In a number of clinical studies, interferon alpha reversed or decreased the rate of fibrosis progression in patients with HCV infection. Evidence suggests that interferon alpha may, at least in the short term, halt disease progression. Furthermore, prospective studies are currently evaluating whether administering low-dose maintenance pegylated interferon prevents fibrotic disease progression in patients with hepatitis C and improves clinical end points.
We report the results of a study that was performed nearly 10 years ago evaluating the efficacy and safety of long-term continuous interferon alpha-2b treatment with repeated 24-week courses in chronic HCV patients who relapse after prior interferon monotherapy. The study was terminated prematurely because a more effective anti-viral combination therapy, interferon and ribavirin, had imminent approval in the United States. In view of the renewed interest in treatments that slow fibrosis progression, we analysed the results of this study and now report the findings.
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