Asian and Caucasian patients respond similarly to pegylated interferon for chronic hepatitis B

Keith Alcorn
Published:
20 May 2013

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 seroconversion.

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 clinical practice.

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 'white' patients.

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 among HBeAg-negatives).

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.

Reference

Marcellin P et al. S-Collate cohort 'real-life' study: efficacy and safety of peginterferon alfa-2a (40kd) in 1233 patients with chronic hepatitis B according to Asian and Caucasian race. 48th International Liver Congress (EASL 2013), Amsterdam, abstract 41, 2013.