Oral treatment for hepatitis B gets approval in United States

Deborah Josefson, San Francisco

The first oral treatment for hepatitis B infection has just received approval from an advisory panel to the Food and Drug Administration in the United States. Lamivudine (Epivir), also known as 3TC, is a nucleoside reverse transcriptase inhibitor that blocks viral replication and is currently used to combat AIDS.

Hepatitis B virus infects about 350 million people worldwide. No cure exists, and current strategies rely on vaccination or treatment with interferon, an immune boosting cytokine. Interferon is administered through injection and causes prominent flu-like side effects, such as hyperpyrexia, myalgias, weakness, fatigue, anorexia, leucopenia, and sometimes depression and hair loss. These factors limit its tolerability.

The advisory panel based its recommendation for approval on the results of four clinical studies conducted by GlaxoWellcome. These trials followed 967 patients with chronic hepatitis B infection. Treatment with lamivudine, 100 mg a day for one year, resulted in regression in the severity of disease as measured by improvements in liver histology and decreases in the levels of transaminases. Additionally, some patients seroconverted to a less active state.

Overall, 52% of patients taking lamivudine showed significant histological improvement compared with 36% of those taking interferon and 25% of those taking placebo. Side effects noted with lamivudine treatment included malaise or fatigue; nausea and vomiting; and headache and abdominal pain. The frequency of these side effects was not significantly greater than with placebo. However, lactic acidosis, hepatomegaly with steatosis, and fatal hepatic failure have been reported in patients taking lamivudine and other antiretrovirals in the past.

Although the advisory committee voted for approval, it cautioned that further studies need to be undertaken. The duration of treatment has not been determined, and some patients, although they had clinically improved, showed increases in hepatitis B virus DNA content, suggesting a higher viral load. Hepatitis flare ups after stopping the drug were also seen. The committee also recommended that trials of interferon plus lamivudine should be conducted to see if there is a synergistic effect between the two treatments.