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INTRODUCTION
Early on-treatment prediction of response to PEG 107
Chronic hepatitis B virus (HBV) infection affects 350 to 400 million people worldwide and
is responsible for 1 million deaths every year. 1 Hepatitis B e antigen (HBeAg-)negative
chronic hepatitis B (CHB) represents a late phase in the course of the infection, which is
recognized worldwide with an increasing prevalence. 2 Therapeutic intervention is often
indicated for HBeAg-negative patients, because spontaneous remission rarely occurs
and patients have more advanced liver disease in comparison with HBeAg-positive
patients. 3
In the last decade great strides have been made in the treatment of CHB, but the
management of the HBeAg-negative type remains diffi cult. Nucleos(t)ide analogues
are able to maintain suppression of viral replication in the majority of HBeAg-negative
patients and are well tolerated, 4-5 but it is highly uncertain whether oral antiviral therapy
can be discontinued. 6-8 In contrast to nucleos(t)ide analogues, one year of peginterferon
therapy can result in an off-treatment sustained response (SR) in HBeAg-negative
patients. 9-10 However, treatment with peginterferon is often complicated by the occurrence
of side effects and a minority of patients with HBeAg-negative disease achieve
SR. It is therefore a major challenge to identify patients who are likely to benefi t from
peginterferon therapy as early as possible during the treatment course.
HBV DNA quantifi cation is widely used as a marker of viral replication to assess response
to nucleos(t)ide analogues, but prediction of response to peginterferon by means of
serum HBV DNA levels is diffi cult. 11-12 Advances in technology have enabled the
development of a quantitative assay for hepatitis B surface antigen (HBsAg). The serum
concentration of HBsAg appears to refl ect the amount of covalently closed circular DNA
(cccDNA) in the liver, which acts as a template for the transcription of viral genes. 13-14
Recently, several studies have suggested that serum HBsAg levels may be indicative of
the likelihood of response to interferon-based therapy. 15-17 The aim of this study was to
clarify the role of early on-treatment quantitative serum HBsAg in the prediction of SR in
HBeAg-negative CHB patients treated with peginterferon alfa-2a.
PATIENTS AND METHODS
Patients
HBsAg levels were measured in sera from a total of 107 of 133 HBeAg-negative chronic
hepatitis B patients who participated in an investigator-initiated, multicenter, randomized,
double-blind, controlled trial. 9 Patients were randomly assigned in a one-to-one
ratio to receive 180 μg peginterferon alfa-2a weekly and ribavirin 1000 mg (body weight