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Chapter 2.1
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DNA was observed in patients who lost HBeAg during PEG-IFN therapy compared
with placebo. A signifi cant difference in HBV DNA decline between the two groups was
already present at week 4, which progressed to an estimated 2 log at week 48. These
fi ndings suggest that HBeAg loss induced by PEG-IFN may be accompanied by a more
profound suppression of viral replication compared with spontaneous HBeAg loss.
Treatment induced and spontaneous fl ares of liver infl ammation are often observed in
patients with CHB. These fl ares appear to refl ect the activity of the host immune system
against the virus. Our study is the fi rst to report that fl ares induced by PEG-IFN are accompanied
with a higher consecutive decline in HBV DNA compared with that observed after
a spontaneously occurring fl are during placebo therapy. As previously reported, a trend
towards a higher chance of HBeAg loss in PEG-IFN treated patients with an on-treatment
fl are was observed. 24 In contrast, the rate of HBeAg loss was similar in placebo-treated
patients with or without fl are. The observation that the decline of HBV DNA was stronger
in patients with fl ares, and also in patients with HBeAg loss, during PEG-IFN therapy compared
with placebo further underlines the importance of the immunomodulatory effects
of PEG-IFN which results in an improved activity of the immune response against HBV.
Although this study is the fi rst to investigate the antiviral effi cacy of PEG-IFN compared
with placebo, it has limitations. Since the treatment groups were derived from two different
randomized controlled trials, their baseline characteristics were not completely
comparable at baseline. Baseline ALT and HBV DNA levels were higher in the PEG-IFN
group. Therefore, we corrected the linear mixed regression analysis of HBV DNA decline
for baseline ALT. Baseline HBV DNA was not associated with the estimated HBV DNA
decline. Furthermore, the distribution of HBV genotypes differed between the two treatment
arms. However, genotypes A-D were present in substantial numbers across both
groups, which allowed us to perform separate analyses of the overall decline of HBV
DNA according to genotype.
In conclusion, PEG-IFN therapy resulted in a larger HBV DNA decline compared with
placebo. The degree of viral suppression was stronger in HBeAg-positive patients who
lost HBeAg or who had an ALT fl are during PEG-IFN therapy compared with spontaneous
HBeAg loss or fl ares during placebo therapy.