Interferon Alpha 2b Plus Ribavirin for Chronic Hepatitis B
Condition: Chronic Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Hepatitis B virus (HBV) causes a wide spectrum of liver diseases, such as fulminant or acute
      hepatitis, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The number of
      individuals infected with this virus has been estimated to be as high as 350 million. Thus,
      in addition to global hepatitis B vaccination, effective treatment of chronic hepatitis B is
      also needed.

      Currently, there are no effective antiviral treatments to cure HBV infection in patients with
      chronic hepatitis B. Five drugs have been approved for the treatment of chronic hepatitis B
      at present: conventional interferon (IFN) alpha, lamivudine, adefovir dipivoxil, pegylated
      IFN alpha and recently entecavir. Overall, satisfactory virologic and serologic responses
      could be achieved using pegylated IFN alpha alone in around 20-44% of these patients.
      Nevertheless, better treatment options are still needed for the remaining >50%
      non-responders.

      Although the best treatment choice for chronic hepatitis B is not clarified yet, certain
      therapeutic concepts could be derived from the experience of treating patients with chronic
      hepatitis C. A major advancement in treating hepatitis C virus (HCV) infection has been the
      development of combination therapy with IFN and ribavirin. IFN monotherapy is limited by poor
      sustained virologic responses, even when higher doses of IFN are used. IFN plus ribavirin
      combination therapy, in contrast, results in much improved treatment outcomes. In our
      previous study and others, sustained remission rate after cessation of therapy were
      significantly higher in patients receiving combination therapy than those receiving IFN
      alone. Therefore, combination therapy with IFN and ribavirin has been recommended as the
      standard treatment regimen for chronic hepatitis C. Furthermore, we have used ribavirin and
      IFN combination for the treatment of dual chronic hepatitis B and C, and the results also
      revealed that the efficacy of clearing HCV RNA was not affected by the presence of HBV
      infection. Interestingly, after a little more than 2-year post-treatment follow-up, we found
      that a significant portion (21%) of the responsive patients also cleared HBsAg. These
      findings imply that this combination regimen might be also effective for the control of
      chronic hepatitis B. We thus conducted a randomized, multi-center, placebo-controlled study
      in patients with HBeAg-positive chronic hepatitis B.
    

Detailed description: 
      Hepatitis B virus (HBV) causes a wide spectrum of liver diseases, such as fulminant or acute
      hepatitis, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The number of
      individuals infected with this virus has been estimated to be as high as 350 million. Thus,
      in addition to global hepatitis B vaccination, effective treatment of chronic hepatitis B is
      also needed.

      Currently, there are no effective antiviral treatments to cure HBV infection in patients with
      chronic hepatitis B. Five drugs have been approved for the treatment of chronic hepatitis B
      at present: conventional interferon (IFN) alpha, lamivudine, adefovir dipivoxil, pegylated
      IFN alpha and recently entecavir. Conventional IFN alpha monotherapy has a narrow range of
      efficacy. Lamivudine, is relatively cheaper, better tolerated, and has been shown to be
      effective in patients with both hepatitis B e antigen (HBeAg)-positive and -negative chronic
      hepatitis B. However, virologic response to lamivudine is not as durable as that occurred
      spontaneously or induced by IFN treatment. In addition, prolonged lamivudine treatment is
      commonly associated with the emergence of drug-resistance HBV mutants accompanied by the
      development of breakthrough hepatitis. Adefovir is potent and has been approved for the
      treatment of chronic hepatitis B in several countries, but is nephrotoxic at daily doses
      higher than 10 mg and is still not available widely. Entecavir, a carbocyclic deoxyguanosine
      analog, which is active against both lamivudine- and adefovir dipivoxil-resistant HBV, is the
      most potent anti-HBV agent ever discovered,11 however, its long-term efficacy remains to be
      evaluated. Pegylated IFN alpha has recently been shown to be superior to conventional IFN
      alpha and lamivudine, and has also been approved for the treatment of chronic hepatitis B.
      Overall, satisfactory virologic and serologic responses could be achieved using pegylated IFN
      alpha alone in around 30-44% of these patients. Nevertheless, better treatment options are
      still needed for the remaining >50% non-responders.

      Although the best treatment choice for chronic hepatitis B is not clarified yet, certain
      therapeutic concepts could be derived from the experience of treating patients with chronic
      hepatitis C. A major advancement in treating hepatitis C virus (HCV) infection has been the
      development of combination therapy with IFN and ribavirin. IFN monotherapy is limited by poor
      sustained virologic responses, even when higher doses of IFN are used. IFN plus ribavirin
      combination therapy, in contrast, results in much improved treatment outcomes. In our
      previous study and others, sustained remission rate after cessation of therapy were
      significantly higher in patients receiving combination therapy than those receiving IFN
      alone. Therefore, combination therapy with IFN and ribavirin has been recommended as the
      standard treatment regimen for chronic hepatitis C. Furthermore, we have used ribavirin and
      IFN combination for the treatment of dual chronic hepatitis B and C, and the results also
      revealed that the efficacy of clearing HCV RNA was not affected by the presence of HBV
      infection. Interestingly, after a little more than 2-year post-treatment follow-up, we found
      that a significant portion (21%) of the responsive patients also cleared HBsAg. These
      findings imply that this combination regimen might be also effective for the control of
      chronic hepatitis B. We thus conducted a randomized, multi-center, placebo-controlled study
      in patients with HBeAg-positive chronic hepatitis B.
    

Intervention name(s): interferon alpha 2b plus ribavirin; interferon alpha 2b plus placebo
Intervention type(s): Drug; Drug
Intervention MeSH terms: Interferons; Ribavirin; Interferon-alpha; Interferon alpha-2
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: hepatitis B virus; e antigen; interferon; ribavirin