Finds Pegylated Interferon Is More Effective than Lamivudine
for Chronic Hepatitis B, but Study Shows Little Activity
against HBV Genotype D
A systemic review of clinical trials found that
pegylated interferon was more effective than the
oral antiviral drug lamivudine
(Epivir-HBV) at achieving endpoints including
hepatitis B virus (HBV) DNA clearance and hepatitis
B "e" antigen (HBeAg) seroconversion,
investigators reported at the 60th Annual Meeting
of the American Association for the Study of Liver
Diseases (AASLD 2009)
this month in Boston. Another study, however,
showed that pegylated
interferon did not work so well against HBV
types of treatment are approved for chronic
hepatitis B, directly targeted oral antiviral agents
such as lamivudine (Epivir-HBV), and conventional or pegylated
interferon, which stimulates immune response to HBV.
Mumtaz from Aga Khan University in Pakistan and colleagues
performed a Cochrane review of pegylated interferon for
chronic hepatitis B in adult patients. The Cochrane Collaboration
is an independent network of experts that produces systematic
reviews of healthcare interventions and promotes evidence-based
investigators searched the Cochrane Hepato-Biliary Group
Controlled Trials Register, the Cochrane Central Register
of Controlled Trials, and the MEDLINE, EMBASE, and LILACS
databases for studies published through January 2009 that
compared pegylated interferon versus other therapies for
adult chronic hepatitis B patients.
researchers identified 7 trials reported in 15 publications,
with a total of 2179 participants.
studies showed evidence that pegylated interferon is
superior to lamivudine in achieving outcomes including:
DNA clearance: rate ratio (RR) 0.94;
DNA suppression: RR 0.85;
seroconversion: RR 0.84;
B surface antigen (HBsAg) loss: RR 0.97.
lamivudine to pegylated interferon did not decrease
the "number needed to treat" in order to produce
a successful outcome.
adverse events were more common with pegylated interferon
than with lamivudine.
on these findings, the researchers concluded, "Current
evidence suggests that pegylated interferon is better than
lamivudine when used alone or with lamivudine."
to a related study reported at the same conference, however,
pegylated interferon is not very effective against chronic
HBV genotype D infection.
Kurdas and colleagues from Turkey -- where genotype D is
the most common form of HBV, accounting for 97% of cases
-- evaluated the efficacy of pegylated interferon in eligible
chronic hepatitis B patients treated at Haydarpasa Numune
Education and Research Hospital between 2004 and 2007.
patients met any 2 of the following criteria: less than
60 years of age, ALT > 2 x upper limit of normal,
HBV DNA < 1 million copies/mL, or fibrosis stage
< 3. Patients with initial HBV DNA levels >
1 million copies/mL were pretreated with lamivudine until
their viral load fell below this level, at which point they
could start pegylated interferon.
total of 28 patients (15 HBeAg positive and 13 HBeAg negative)
were enrolled in the study and treated with 180 mcg/week
alfa-2a (Pegasys) or 1.5 mcg/kg/week pegylated
interferon alfa-2b (PegIntron) for 48 weeks. Participants
were followed for an average of 115 weeks after the end
week 12, 40% of HBeAg positive patients and 70% of HBeAg
negative patients experienced at least a 2 log reduction
in HBV viral load. At the end of treatment, 39% and 67%,
respectively, had undetectable HBV DNA. However, only 3
HBeAg negative patients and none of the HBeAg positive participants
achieved sustained virological response after completing
therapy. Because of the small numbers, the differences between
the HBeAg positive and HBeAg negative groups were not statistically
significant. Overall, 10 patients (63%) achieved HBeAg seroconversion,
but none achieved HBsAg seroconversion.
findings led the investigators to conclude that, "Pegylated
interferon therapy was found ineffective in patients with
chronic hepatitis B genotype D despite young age, high ALT,
low viral load, and low fibrosis scores."
Mumtaz, S Hamid, and SM Jafri. Pegylated interferon for
chronic hepatitis B in adults: a Cochrane Review. 60th Annual
Meeting of the American Association for the Study of Liver
Diseases (AASLD 2009). Boston. October 30-November 1, 2009.
Kurdas, F Guzelbulut, Y Gökden, and others. PegIFNs
are not satisfactory in genotype D chronic HBV infection.
60th Annual Meeting of the American Association for the
Study of Liver Diseases (AASLD 2009). Boston. October 30-November
1, 2009. Abstract 462.