Pegylated Interferon Monotherapy for Treatment of Chronic Hepatitis B

Chronic hepatitis B virus (HBV) infection is a serious clinical problem and a major cause of liver-related morbidity and mortality. Despite the widespread availability of a safe and effective vaccine to prevent HBV infection, newly diagnosed infections remain common. Therefore effective treatment of chronic hepatitis B is of vital importance.

At the 13th International Symposium on Viral Hepatitis and Liver Disease (ISVHLD) held in Washington, DC, March 20-24, 2009, invited experts presented their views on a variety of important issues related to the treatment and management of hepatitis B and hepatitis C.

Dr. H.L.A. Janssen of the Department of Gastroenterology and Hepatology at the University Hospital Rotterdam, Netherlands, summarized his opinions regarding the use of pegylated interferon alfa (peginterferon) monotherapy for the treatment of chronic hepatitis B. Following is an edited summary of his remarks.

PegInterferon for Chronic Hepatitis B

The practicing clinician is currently faced with a number of effective treatment options for chronic hepatitis B, including two formulations of interferon (standard interferon and pegylated interferon) and five nucleoside/nucelotide analogues (lamivudine [Epivir-HBV], adefovir [Hepsera], entecavir [Baraclude], telbivudine [Tyzeka], and tenofovir [Viread]).

The attachment of a polyethylene glycol (PEG) molecule to interferon led to improved pharmacokinetic properties. A significant increase in half-life allowed administration once weekly, resulting in a relatively continuous drug exposure during the dosing interval.

Two pegylated interferons have been developed: a small linear 12 kDa PEG, linked to interferon-a2b (pegylated interferon alfa-2b [PegIntron]), and a large branched 40kDa PEG, linked to interferon alfa-2a (pegylated interferon alfa-2a [Pegasys]).

Pegylated interferon alfa-2a is licensed globally for the treatment of chronic hepatitis B while pegylated interferon alfa-2b is licensed only in specific high endemic countries.

Treatment strategies can be divided into those aiming for sustained response after discontinuation of therapy versus responses that need to be maintained by prolonged antiviral therapy. Sustained response is particularly achieved with interferon-based therapy, while treatment-maintained response can be achieved with long-term nucleoside/nucleotide analogue therapy in the majority of patients.

Although the nucleoside/nucleotide analogues are much more potent antivirals than pegylated interferon, of currently available drugs for the treatment of chronic hepatitis B, pegylated interferon seems to result in the highest rate of off-treatment sustained response after a one-year course of therapy.

Sustained transition to the immune-control phase (inactive HBsAg carrier state) can be achieved in approximately 30-35% of HBeAg positive patients and 20-25% of HBeAg negative patients. Loss of HBsAg has been observed in 11% of both HBeAg positive and HBeAg negative patients after 3-4 years. Aiming for sustained response is of particular interest because many HBV-infected patients are in need of antiviral therapy at young age and may otherwise require indefinite treatment.

In general, pegylated interferon therapy should be considered in all HBV genotype A infected patients. In patients harboring HBV genotypes B and C, the pros and cons of the available drugs as well as patient-specific characteristics (in particular HBV DNA and AST levels) should be carefully balanced.

Pegylated interferon should only be offered to highly motivated HBeAg positive or negative patients with HBV genotype D, since sustained response rates are generally rather low. Since the evidence of the influence of HBV genotype on choice of antiviral therapy in chronic hepatitis B is increasing, determination of HBV genotype appears essential in patients in whom sustained off-treatment response is pursued.

Combining pegylated interferon or other immunomodulators with an antiviral agent theoretically offers advantages. The addition of lamivudine to pegylated interferon therapy, however, did not result in higher sustained response rates. Combination treatment with pegylated interferon and new potent nucleoside/nucleotide analogues, or different combination regimens, may improve treatment outcome.

4/07/09

Reference
HLA Janssen. Peg-Interferon for Chronic Hepatitis B. 13th International Symposium on Viral Hepatitis and Liver Disease (ISVHLD). Washington, DC. May 20-24, 2009. Abstract SP-22.