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Chapter 2.5
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peginterferon and nucleos(t)ide analogues as initial treatment options 20, 22-23 , but the
optimal choice for individual patients remains controversial. Due to the higher chance
of disease relapse after treatment discontinuation peginterferon is relatively less often
prescribed to HBeAg-negative as compared to HBeAg-positive patients. A treatment
course with peginterferon should however be considered for HBeAg-negative patients
with a high likelihood of response, because a fi nite treatment course can lead to an
off-treatment SR. Otherwise prolonged or indefi nite treatment with a nucleos(t)ide
analogue is likely. Unfortunately, baseline predictors of response to peginterferon are
poorly defi ned in comparison with HBeAg-positive disease. 24-25 One study reported
that baseline serum HBV DNA and ALT levels, patient age and gender, and infecting
HBV genotype were signifi cantly associated with response to peginterferon alfa-2a with
or without lamivudine therapy, 26 but this was not confi rmed in our patient population.
Recent studies on peginterferon in HBeAg-negative patients have focussed on the
identifi cation of markers allowing on-treatment prediction of response. 15-17
We found that accurate prediction of SR to peginterferon for HBeAg-negative disease in
an early treatment phase is not possible based on serum HBsAg levels alone. However,
combining on-treatment declines in serum HBsAg and HBV DNA concentration resulted
in a solid stopping rule. At week 12, the absence of a decline in HBsAg level combined
with less than 2 log copies/mL decrease in HBV DNA level identifi ed a substantial proportion
of the total study population (20%) in which therapy could be discontinued without
losing sustained responders. In contrast, patients in whom both declines were present
had the highest probability of SR (39%). This patient group should be encouraged to
complete the 48-week treatment phase because they are the most likely group to benefi
t from therapy. Table 2 provides recommendations for (dis)continuation of therapy for
patient groups based on the chance of developing SR. Obviously, the fi nal decision to
(dis)continue therapy is at the discretion of the treating physician, taking into account
other factors like drug tolerability as well. Another important fi nding is that a guiding
rule before 12 weeks of therapy could not be established because discrimination of
Table 2. Recommendations for continuation of peginterferon alfa-2a therapy for HBeAg-negative CHB
at week 12.
Week 12 versus baseline
HBsAg decline
HBV DNA decline
≥2 log copies/mL
Chance of SR Recommendation to continue
no no Absent stop
no yes Intermediate continue
yes no Intermediate continue
yes yes High
strong recommendation
for continuation