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INTRODUCTION
PEG-IFN versus placebo for HBeAg-positive CHB 29
More than 350 million people worldwide are chronically infected with the hepatitis B virus
(HBV) and are at risk for cirrhosis, liver failure and hepatocellular carcinoma. 1 Hepatitis B
e antigen (HBeAg-)positive chronic hepatitis B (CHB) is regarded as the earliest phase of
infection. 2 Treatment is generally recommended for patients with HBeAg-positive CHB
who do not clear HBeAg spontaneously, have high serum HBV DNA levels and persistently
elevated alanine aminotransferase (ALT) levels. 3-4 First-line treatment options
consist of third generation nucleos(t)ide analogues (NA), including entecavir (ETV) and
tenofovir (TDF), and peginterferon alfa (PEG-IFN). 3-4 ETV and TDF are potent inhibitors
of the HBV polymerase activity and are highly effective in maintaining suppression of
HBV replication. 5-6 In contrast, PEG-IFN therapy aims at the induction of a sustained
off-treatment response through its immunomodulatory effects, but only has a modest
direct antiviral effect. 7 Consequently, one year of PEG-IFN therapy in patients with
HBeAg-positive CHB resulted in 2.3-4.5 log copies/mL decline of HBV DNA, 8-9 while
there was a 6.2-6.9 log drop of HBV DNA after 1 year of therapy with third generation
NA. 5-6 In contrast to suppression of HBV DNA, HBeAg loss as a marker of immunological
control was observed more often in patients treated with PEG-IFN compared with NA
(29-30% versus 21-22%). 5-6, 8-9
Fluctuations in HBV DNA and alanine aminotransferase (ALT) levels occur spontaneously
during the natural course of CHB, 10 and spontaneous HBeAg clearance occurs at
an annual rate of 10–15% in adults with elevated ALT levels. 11 Furthermore, the clinical
signifi cance of different HBV genotypes for the natural course and treatment response
of CHB has become increasingly recognized in recent years. 12-15 Nevertheless, extensive
viral kinetics data during PEG-IFN therapy have not been compared to natural occurring
fl uctuations in viral load during placebo therapy in patients with HBeAg-positive CHB.
Therefore, the aim of our study was (1) to compare the pattern of HBV DNA decline
between HBeAg-positive patients treated with PEG-IFN alfa-2b and placebo, particularly
in patients achieving HBeAg loss and (2) to study the association between HBV
genotype and on-treatment ALT levels with HBV DNA kinetics.
PATIENTS AND METHODS
Patients
A total of 136 patients treated with PEG-IFN alfa-2b monotherapy and 167 patients who
received placebo within two randomized controlled trials were included in this study. 10,
16 The inclusion and exclusion criteria of both trials have been reported in detail previously.
10, 16 In summary, patients were eligible for the original PEG-IFN trial if they had