Some Asian people with chronic hepatitis B treated
with pegylated interferon may experience better outcomes on certain measures
than Caucasians, though overall response rates are similar, according to a
comparative analysis presented at the 48th International Liver Congress (EASL 2013) last month in Amsterdam. The study
also showed that early hepatitis B surface antigen (HBsAg) decline is a
predictor of treatment response in some patients.
Nucleoside/nucleotide analogue antiviral drugs such as
lamivudine (3TC or Epivir), entecavir
(Baraclude) and tenofovir (Viread) are the mainstay of treatment
for chronic hepatitis B virus (HBV) infection. Pegylated interferon is
recommended in international guidelines, but used less often due to cost and
side-effects. While antivirals are effective at suppressing viral replication,
interferon may increase the likelihood of HBV antigen loss and antibody
Patrick Marcellin from University
Paris-Diderot presented findings from S-Collate, a prospective multinational study
of a 'real-life' cohort of people with chronic hepatitis B. The primary aim of
the study was to evaluate on-treatment predictors of HBsAg clearance in routine
Previous studies have shown that a 10% or
greater decline in HBsAg by week 24 of treatment was associated with sustained
immune control among hepatitis B 'e' antigen (HBeAg)-negative patients, as was
a 24-week HBsAg level below 1,500 IU/mL among HBeAg-positive patients.
This analysis also looked at treatment
outcomes according to Asian vs Caucasian race/ethnicity. Hepatitis B is
endemic throughout much of Asia, with many people infected early in life
through mother-to-child transmission.The meaning of 'Asian' and 'Caucasian'
generated some discussion among attendees, who noted that people from the
Indian subcontinent may be geographically Asian but anthropologically
Caucasian; for the most part the study appeared to compare east Asian vs
The study included 592 HBeAg-positive chronic hepatitis C patients (455 Asian and 137
Caucasian) and 641 HBeAg-negative patients (224 Asian and 417 Caucasian). About
70% overall were men. The mean age was a bit younger in the HBeAg-positive
compared with the HBeAg-negative group (about 31 vs 38 years). Duration of infection
was longer for Asians than Caucasians (about 16 vs 12 years)and perinatal
acquisition was more common (about 80 vs 30%). Asians also had higher ALT
liver enzyme levels (183 vs 142 IU/L among HBeAg-positives, 148 vs 101 IU/L
Participants were followed for 24 weeks
before starting treatment with 180mcg/week pegylated interferon alfa-2a (Pegasys) monotherapy
for 48 weeks. Follow-up will continue through three years post-treatment;
Marcellin reported six-month post-treatment findings.
Looking at HBeAg-positive patients, overall
response rates at six months post-treatment were "similar for all
endpoints" between Asians and Caucasians. Half in both groups reached HBV
DNA levels below 2000 IU/mL, while 17 vs 27% fell below 80 IU/mL (approaching
statistical significance; p=0.07). HBV DNA below 2000 IU/mL plus ALT normalisation
was observed in 41 and 37%, respectively, while 20 and 28% achieved low viral
load plus HBeAg loss. However, only 5 and 6%, respectively achieved HBsAg
loss, while 13 vs 9% reached HBsAg levels below 100 IU/mL. Despite these
similarities, Asians experienced a significantly greater decline in HBsAg from
baseline than Caucasians, 1.35 vs 0.33 log, respectively.
Turning to HBeAg-negative participants, Asians
were significantly more likely than Caucasians to achieve HBV DNA below 2000
IU/mL either alone (65 vs 53%) or in conjunction with ALT normalisation (57
vs 37%). However, six-month post-treatment response rates were statistically
similar between Asians and Caucasians with regard to HBV DNA below 80 IU/mL
(32 vs 23%), HBsAg loss (8 vs 4%) and HBsAg below 100 IU/mL. In contrast
with the HBeAg-positive patients, HBeAg-negative Asians and Caucasians had the
same declines in HBsAg from baseline, 0.54 and 0.55log, respectively.
Treatment safety and tolerability did not
differ between Asian and Caucasian patients. Rates of overall side-effects and
serious adverse events were similar, at 5 and 4%, respectively, discontinued
treatment due to adverse events.
"In a 'real-life' setting, response
rates to [pegylated interferon alfa-2a] were not different between Asian and
Caucasian patients with chronic hepatitis B," the researchers concluded,
although they noted that more HBeAg-negative Asian patients achieved both low
HBV DNA and ALT normalisation.
"Early on-treatment HBsAg decline
showed utility as a predictor of response six months post-treatment in
HBeAg-positive Asian patients," they added.