Hansen from Erasmus University Medical Center in Rotterdam
and colleagues aimed to develop a model that could better
predict at baseline which chronic hepatitis B patients would
respond to pegylated interferon,
and to establish an early indicator for when treatment should
Pegylated interferon leads to virological response (undetectable
HBV DNA) and hepatitis B "e" antigen (HBeAg) loss
in only a minority of patients with HBeAg positive chronic
hepatitis B. The treatment is expensive and can cause difficult
side effects, so clinicians want to know when to stop therapy
that is unlikely to produce a favorable outcome.
Known baseline predictors of response to pegylated interferon
include HBV genotype (B responds better than D), pre-treatment
HBV viral load, and alanine aminotransferase (ALT) level.
The investigators looked at whether viral load reduction early
in treatment also has predictive value.
This analysis included 136 chronic hepatitis B patients treated
with pegylated interferon. Response was defined as HBV DNA
< 10,000 copies/mL and HBeAg loss 26 weeks after completion
of treatment. The researchers used logistic regression analysis
to develop a dynamic prediction model using HBV DNA during
the first 32 weeks of therapy.
researchers identified an early clinically useful rule
for continuation or discontinuation of treatment, with
a grid of cut-off values for HBV DNA decline during treatment.
HBV DNA decline at weeks 4, 12, and 24 to baseline factors
improved predictions of sustained response.
DNA decline of at least 2?log(10), or 100-fold, within
24 weeks of starting therapy was strongly associated with
response when added to baseline predictors.
findings led the study authors to conclude, "A dynamic
model including HBV DNA decline during treatment provides
more accurate predictions of response to pegylated interferon."
"The model strongly supports individual decision making
on treatment (dis)continuation in patients with HBeAg positive
chronic hepatitis B," they continued. "It is recommended
that pegylated interferon treatment is stopped by 24 weeks
if HBV DNA declined < 2?log(10)."
Investigator affiliations: Departments of Gastroenterology
& Hepatology, Biostatistics, and Public Health, Erasmus
MC, University Medical Center Rotterdam, Rotterdam, Netherlands;
Department of L-Biostat, Catholic University of Leuven, Leuven,
BE Hansen, EHCJ Buster, EW Steyerberg, and others. Prediction
of the response to peg-interferon-alfa in patients with HBeAg
positive chronic hepatitis B using decline of HBV DNA during
treatment. Journal of Medical Virology 82(7): 1135-1142