Clinical

Peginterferon more effective than lamivudine for chronic hepatitis B

Last Updated: 2005-06-30 16:10:20 -0400 (Reuters Health)

NEW YORK (Reuters Health) - In patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, treatment with peginterferon alfa-2a or peginterferon alfa-2a plus lamivudine is superior to lamivudine monotherapy in reducing viral load and inducing seroconversion of HBeAg and hepatitis B surface antigen (HBsAg), investigators report.

The findings, which appear in The New England Journal of Medicine for June 30, are based on a multicenter study of patients who were randomized to receive peginterferon alfa-2a (180 microgram/week) plus placebo (n = 271), peginterferon alfa-2a plus lamivudine (100 mg daily, n = 271) or lamivudine plus placebo (n = 272) for 48 weeks, followed by 24 weeks of treatment-free follow-up.

Lead author Dr. George K. K. Lau, from the University of Hong Kong, and his associates report that, after 48 weeks, 52% treated with peginterferon alfa-2a monotherapy achieved hepatitis B DNA suppression to < 100,000 copies/mL, as did 86% of those receiving dual therapy and 62% of those taking lamivudine.

After 72 weeks, corresponding rates of viral load suppression were 32, 34%, and 22%. Both peginterferon alfa-2a groups were significantly more effective at reducing levels of virus than lamivudine (p = 0.01 and 0.003, respectively).

At 72 weeks, 41%, 39% and 28% of patients, respectively, had normalized levels of alanine aminotransferase. Corresponding rates of HBeAg seroconversion were 32%, 27% and 19%. HBsAg seroconversion occurred in 16 of those on peginterferon alfa-2a and in none of those on lamivudine monotherapy, the authors note.

Serious adverse events occurred in 4% of the peginterferon alfa-2a group, 2% of the lamivudine group and 6% of the dual therapy group. Two patients receiving lamivudine monotherapy had hepatic decompensation, leading to liver transplantation in one and death in the other.

"The ability to achieve HBeAg and HBsAg seroconversion after a defined period of peginterferon alfa-2a therapy supports the use of peginterferon alfa-2a as a first-line therapy for patients with HBeAg-positive chronic hepatitis B," Dr. Lau's team concludes.

In a related editorial, Dr. Anna Suk-Fong Lok, from the University of Michigan Medical Center in Ann Arbor, points out that "treatment is recommended for patients with high HBV DNA levels, but it is unclear whether patients with low hepatitis B DNA levels will derive the same benefits."

"Given the propensity for hepatitis B virus to persist," she adds, "patients should be closely monitored when treatment is stopped, to avoid fatal flares."

N Engl J Med 2005;352:2682-2695,2743-2746.