Interferon Monotherapy for Treatment of Chronic Hepatitis B
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.
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.
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.
for Chronic Hepatitis B
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
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
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]).
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
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.
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.
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.
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.
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.
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.
Janssen. Peg-Interferon for Chronic Hepatitis B. 13th International Symposium
on Viral Hepatitis and Liver Disease (ISVHLD). Washington, DC. May 20-24, 2009.