CHRONIC HEPATITIS B VIRUS INFECTION IN CHILDREN
Giorgina Mieli-Vergani*, Diego Vergani **
Institute of Liver Studies, King's College Hospital, London. *, Institute of Liver Studies, King's College Hospital, London. **
The probability of becoming a chronic HBV carrier is correlated to the age at infection and the efficiency of the immune system, being highest in children infected within the first year of life, who tend to become 'tolerant' to the virus. Thus, more than 90% of infected infants, including the 5% who do not respond to HBV vaccination, become chronic carriers as compared to 6-10% if the infection occurs after the 6 th year of life. Chronically infected children are usually asymptomatic with normal or minimally abnormal liver function tests, but their liver histology often shows progressive inflammatory changes. Besides posing a serious infection risk to the community, chronically HBV infected children, particularly if male, have a high risk of progressing to cirrhosis and hepatocellular carcinoma, the likelihood of developing these complications being correlated to the length of time to achieve anti-HBe seroconversion. Spontaneous HBeAg loss in chronically infected children occurs at an annual rate of 10-16%, while spontaneous loss of HBsAg is as low as 0.6% per year, the children achieving earlier seroconversion being those with biochemical and/or histological evidence of active disease. Annual HBsAg clearance rate is significantly higher in those children who are already anti-HBe positive (= low viral load), than in those with HBeAg (= high viral load). A treatment able to speed up anti-HBe seroconversion would therefore have a major impact in avoiding the spread of infection and serious complications. Interferon or lamivudine? Treatments do accelerate spontaneous HBeAg clearance. HBeAg loss has been shown in 30-40% of Caucasoid children with chronic HBV infection (usually infected horizontally in childhood) at the end of short courses of IFN-a or lymphoblastoid IFN, but in only 8% of Chinese children (usually infected at birth). Baseline features predicting HBe clearance during IFN treatment are the same that are associated with a higher rate of spontaneous seroconversion; histologically active disease, high transaminase activity and low HBV DNA levels.

With HBV vaccination, horizontal HBV infection is become rarer, while infants infected because of vaccine failure, i.e. 5% of the vaccinated children overall, but 15% of babies of HBeAg positive mothers, represent an increasing proportion of the infected pool. A treatment strategy efficient in inducing HBV immune control in these 'tolerant' children is highly desirable. Combining the anti-viral effect of lamivudine with the immune boosting action of IFN offers a rational therapeutic approach for these children. In a pilot study performed in our Unit, 23 'low responder' children, all infected during the first year of life were treated for 8 weeks with lamivudine, and then for 10 months with lamivudine and interferon alpha 2b. Five children seroconverted to anti-HBe during a 6-month follow up, and 4 cleared HBsAg and became persistently anti-HBs positive.
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