- Category: HBV Treatment
- Published on Wednesday, 08 May 2013 00:00
- Written by Liz Highleyman
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 EASL 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 analog 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 is used less often due to cost and side effects. While antivirals are effective at suppressing viral replication, interferon may increase the likelihood of serological responses involving 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 versus 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 180 mcg/week pegylated interferonalfa-2a (Pegasys) monotherapy for 48 weeks. Follow-up will continue through 3 years post-treatment; Marcellin reported 6 month post-treatment findings.
- Looking at HBeAg positive patients, overall response rates at 6 months post-treatment were "similar for all endpoints" between Asians and Caucasians.
- Half in both groups reached HBV DNA levels < 2000 IU/mL, while 17% vs 27% fell to < 80 IU/mL (approaching statistical significance).
- HBV DNA < 2000 IU/mL plus ALT normalization 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% and 9% reached HBsAg levels < 100 IU/mL.
- Despite these similarities, Asians experienced a significantly greater decline in HBsAg from baseline compared with Caucasians, 1.35 vs 0.33 log, respectively.
- 39% of patients with HBsAg levels <1500 IU/mL at treatment week 12 achieved both HBeAg loss and low HBV DNA, compared with 14% of those with 1500-20,000 IU/mL and 8% of those with > 20,000 IU/mL.
- 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 normalization (57% vs 37%).
- However, 6 month post-treatment response rates were statistically similar with regard to HBV DNA < 80 IU/mL (32% vs 23%), HBsAg loss (8% vs 4%), and HBsAg < 100 IU/mL (18% vs 13%).
- In contrast with the HBeAg positive patients, HBeAg negative Asians and Caucasians had the same declines in HBsAg from baseline, 0.54 and 0.55 log, respectively.
- Treatment safety and tolerability did not differ between Asian and Caucasian patients.
- Rates of overall side effects and serious adverse events were similar, and 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 Asia 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 normalization.
"Early on-treatment HBsAg decline showed utility as a predictor of response 6 months post-treatment in HBeAg-positive Asian patients," they added.
This study conflicts with the common belief that Asian hepatitis B patients are "harder-to-treat." "I think response to interferon in Asians is similar to -- and maybe even better than -- [that of] Caucasians," Marcellin said.
P Marcellin, Q Xie, T Piratvisuth, 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 Annual Meeting of the European Association for the Study of the Liver (EASL 2013). Amsterdam. April 24-28, 2013. Abstract 41.