HBsAg Decline Predicts Sustained Response to Pegylated Interferon;
Extended Treatment Can Improve Outcomes
Chronic hepatitis B patients who experience an
early decrease in hepatitis B surface antigen
(HBsAg) starting before week 24 of therapy are
more likely to achieve sustained response to pegylated
interferon alfa-2a (Pegasys), according to
an analysis presented at the 60th Annual Meeting
of the American Association for the Study of Liver
Diseases (AASLD 2009)
this month in Boston. Another study showed that
extending pegylated interferon treatment to 72
weeks for hepatitis B "e" antigen (HBeAg)
positive patients who did not achieve a response
at week 48 could lead to HBeAg seroconversion
and HBsAg clearance.
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 stimulate immune response to HBV.
Brunetto and a team of European colleagues investigated
patterns of on-treatment HBsAg decline in patients with
HBeAg negative chronic hepatitis B treated with pegylated
interferon, with or without lamivudine, and their influence
on post-treatment sustained response rates.
48-week course of pegylated interferon alfa-2a produces
on-treatment reduction of serum HBsAg in chronic hepatitis
B patients, the researchers noted as background. Since HBsAg
decline is associated with sustained response, monitoring
on-treatment HBsAg levels might help identify patients most
likely to benefit from this therapeutic approach.
investigators measured quantitative serum HBsAg levels at
baseline and at weeks 12, 24, 48, and 72 in patients treated
with 180 mcg/week pegylated interferon alfa-2a for 48 weeks,
with or without 100 mg once-daily lamivudine. Post-treatment
response was assessed at 6 months in 155 patients and at
5 years in 120 patients who entered a long-term observational
study. HBsAg decline was defined as a 10% reduction from
of patients experienced a continuous HBsAg decline from
baseline to week 24 and to week 48.
experienced no HBsAg decline at week 24, but had a late
decline by week 48.
were relapsers, experiencing HBsAg decline at week 24
but not at week 48.
experienced no HBsAg decline at week 24 or at week 48.
overall sustained virological response rate at 6 months
post-treatment was 45%.
response was highest in patients with continuous (60%)
or late (48%) HBsAg decline, compared with HBsAg relapse
(29%) or no decline (20%).
5 years post-treatment, virological response was more
durable among patients with continuous decline (38%)
compared with late decline (21%), relapse (17%), or
no decline (9%).
of patients with continuous decline, 10% with late decline,
17% with relapse, and 0% with no decline achieved HBsAg
clearance at 5 years.
"On-treatment HBsAg decline is associated with sustained
post-treatment response to Pegasys with highest response
rates in those with continuous decline in HBsAg levels,"
the investigators concluded.
post-treatment response appeared to be less durable in patients
with late HBsAg decline starting after week 24; however
some patients with a late decline achieved HBsAg clearance,"
on these findings, they recommended, "Further studies
are warranted to determine if patients with a late HBsAg
decline may benefit from extending Pegasys treatment beyond
the standard 48-week course."
Epatologia, Azienda Ospedaliero Pisana, Pisa, Italy; Service
d'Hepatologie and Centre de Recherches Biologiques Beaujon,
University of Paris, Clichy, France; Direzione Scientifica,
Foundation IRCCS, Policlinico di Milano and University of
Pisa, Pisa, Italy; Abbott GmbH & Co, Wiesbaden, Germany;
IST GmbH , Mannheim, Germany; Hoffman-La Roche Ltd, Basel,
a related study, X.P. Chen from China assessed the potential
benefits of extending pegylated interferon therapy to 72
weeks in chronic hepatitis B patients who did not respond
after 48 weeks of treatment.
this open-label study, 67 HBeAg positive patients with normal
or mildly elevated ALT were randomly assigned to receive
either 180 mcg/week pegylated interferon alfa-2a for 48
weeks or the oral antiviral drug entecavir
(Baraclude) at 0.5 mg/day for 72 weeks.
total of 12 patients in the pegylated interferon arm who
did not achieve HBeAg seroconversion, HBV DNA < 1000
copies/mL, or HBsAg < 1500 IU/mL by week 48 continued
on the same regimen for a further 24 weeks (for a total
of 72 weeks).
week 72, 44% of patients in the pegylated interferon
arm achieved HBeAg seroconversion, compared with 18%
in the entecavir arm.
and 3%, respectively, experienced HBsAg clearance.
week HBeAg seroconversion response rates were higher
among pegylated interferon recipients with elevated
baseline ALT compared than among those with normal ALT
(52% vs 23%, respectively).
rates of HBeAg seroconversion were observed in patients
with HBsAg < 1500 IU/mL at weeks 12 and 24 (75% and
"Pegasys was superior to entecavir in achieving HBeAg
seroconversion and HBsAg clearance at week 72," the
investigators concluded. "Patients without a response
to pegylated interferon at week 48 achieved HBeAg seroconversion
and HBsAg clearance when therapy was extended."
Academy of Medical Science, Guangdong General Hospital,
Brunetto, P Marcellin, F Bonino, and others. HBsAg decline
in HBeAg-negative patients treated with peginterferon alfa-2a
is associated with sustained response up to 5 years post-treatment:
patients with continuous HBsAg decline starting before week
24 achieve highest rates of response. 60th Annual Meeting
of the American Association for the Study of Liver Diseases
(AASLD 2009). Boston. October 30-November 1, 2009. Abstract
Chen, X Chen, J Huang, and others. Extending peginterferon
alfa-2a therapy in patients with HBeAg-positive chronic
hepatitis B who did not achieve a response at week 48 can
lead to HBeAg seroconversion and HBsAg clearance. 60th Annual
Meeting of the American Association for the Study of Liver
Diseases (AASLD 2009). Boston. October 30-November 1, 2009.