Clinical

"Immunotolerant" children with hepatitis B respond to combination treatment

Last Updated: 2006-03-20 16:11:33 -0400 (Reuters Health)

By Clementine Wallace

NEW YORK (Reuters Health) - Combining the antiviral effect of lamivudine with the immune-boosting action of interferon-alpha (IFN-alpha) can result in complete viral control of hepatitis B in "immunotolerant" children -- those who were infected in infancy and became chronic carriers -- according to findings from a pilot study.

"Our results are provocative in that they challenge the widely held view that hepatitis B immunotolerant newborns are unlikely to respond to antiviral therapy and should therefore not be considered for treatment," Dr. Giorgina Mieli-Vergani, from King's College Hospital in London, told Reuters Health. "If what we suggest is correct, it's going to require a huge change because there are a lot of children who are currently not being treated."

Most new cases of viral hepatitis B (HBV) infection occur in infancy, note Dr. Mieli-Vergani and colleagues in the February issue of The Journal of Pediatrics. Approximately 90% of these children become chronic carriers, which is associated with a high risk of cirrhosis and hepatocellular carcinoma later in life.

In fact, "These children have a 25% lifetime risk of developing liver cancer," Dr. Mieli-Vergani said.

The investigators explain that IFN-alpha is less effective (and therefore often not offered) in children who acquired the infection vertically or during the first year of life, than in children and adults with active disease and low HBV DNA levels.

"Past trials in adults and children have shown that those who respond to any type of hepatitis B treatment are those who already have active disease," said Dr. Mieli-Vergani.

Her team conducted a trial of 8-weeks of lamivudine pretreatment followed by a combination of lamivudine and IFN-alpha for 10 months, in 23 children infected with hepatitis B perinatally. All the children, mean age 10 years, had the characteristics of poor responders -- normal aminotransferase levels, minimal liver inflammation, and high HBV-DNA.

At the end of the treatment, 78% of children had become HBV-DNA negative, and no serious adverse events were observed. Five children (22%) seroconverted to anti-HBe, and four of them (17%) achieved complete viral control, becoming HBsAg negative and anti-HBs positive on the long run. The viral status of these patients had not changed after a 40-month follow-up.

"This is only a pilot study of 23 children, but the message that comes out is that trials should be designed to follow-up on our findings, to prove whether or not these children could benefit from an early treatment," Dr. Mieli-Vergani concluded.

J Pediatr 2006;148:228-233.