By Liz Highleyman

Unlike most antiviral agents used to treat chronic hepatitis B virus (HBV) infection, pegylated interferon promotes immune response rather than directly targeting the HBV lifecycle.

At the 43rd annual meeting of the European Association for the Study of the Liver (EASL) this week in Milan, an international team of researchers presented 4-year follow-up data from a study of pegylated interferon alfa-2a (Pegasys) with or without lamivudine (Epivir-HBV) in patients with hepatitis B "e" antigen (HBeAg) negative HBV -- a group with poorer prognosis and a higher rate of relapse than people with HBeAg positive virus.

The trial included 537 patients with HBeAg negative chronic hepatitis B randomly assigned to receive 180 mcg/week pegylated interferon plus placebo (n = 177), pegylated interferon plus 100 mg/day lamivudine (n = 179), or lamivudine alone (n = 181) for 48 weeks.

At the end of the initial study, 230 of the 356 participants treated with pegylated interferon with or without lamivudine and 85 of the 181 patients treated with lamivudine monotherapy participated in a roll-over observational study to assess continued response during long-term follow up.

The investigators previously reported that patients treated with pegylated interferon with or without lamivudine achieved significantly higher rates of virological response, alanine aminotransferase (ALT) normalization, and hepatitis B surface antigen (HBsAg) clearance compared to those treated with lamivudine monotherapy 3 years post-treatment.

Year 4 Results

• 4 years post-treatment, virological response rates in the pegylated interferon arms were 24% for both HBV DNA < 20,000 copies/mL (about 4,000 IU/mL) and < 10,000 copies/mL (about 2,000 IU/mL).

• 17% of patients who received pegylated interferon achieved HBV DNA < 400 copies/mL versus 7% of those who received lamivudine alone.

• ALT normalization occurred in 27% of patients treated with pegylated interferon with or without lamivudine, compared to 16% of those treat with lamivudine monotherapy.

• The rate of HBsAg clearance continued to increase during follow-up in the pegylated interferon arms, reaching 11% by year 4, compared with 2% in the lamivudine monotherapy arm.

• HBsAg clearance occurred in 35% of patients in the pegylated interferon arms who achieved HBV DNA of 400 copies/mL or less 24 weeks post-treatment, but only in 3% of those with HBV viral load > 400 copies/mL.

• By contrast, none of the 7 lamivudine monotherapy patients who achieved HBV DNA of 400 copies/mL or less 24 weeks post-treatment cleared HBsAg.

Conclusion

Based on these findings, the researchers concluded, "Over a 4-year follow-up period, a 1-year course of peginterferon alfa-2a provided durable ALT normalization and HBV DNA suppression in around [one-quarter of] patients with HBeAg-negative chronic hepatitis B."

"This, together with its ability to induce, during follow up, increasing rates of HBsAg clearance, supports its use as first-line therapy in patients with HBeAg-negative chronic hepatitis B," they added.

Service D'Hepatologie, INSERM Unite 481 And Centre De Recherches Claude Bernard Sur Les Hepatite Virales, Hopital Beaujon, Clichy, France; NKC Institute of Gastroenterology and Hepatology, Department of Internal Medicine, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand; UO Gastreonterologia ed Epatologia, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy; Scientific Direction, Foundation IRCCS Policlinico of Milan and University of Pisa, Pisa, Italy; Department Of Medicine, Queen Mary Hospital, University of Hong Kong, China; Universita di Cagliari, Italy; University of Ankara, Turkey; Roche, Dee Why, Australia and Basel, Switzerland.

4/25/08

Reference
P Marcellin, T Piratvisuth, M Brunetto, and others. Virological and Biochemical Response in Patients with HBeAg-Negative Chronic Hepatitis B Treated with Peginterferon Alfa-2a (40kd) with or without Lamivudine: Results of 4-Year Follow-Up. 43rd annual meeting of the European Association for the Study of the Liver (EASL 2008). Milan, Italy. April 23-27, 2008.