Chronic hepatitis B in children

Abstract

Chronic hepatitis B affects more than 350 million people. In areas of high and intermediate endemicity, hepatitis B virus (HBV) infection is mainly contracted in the perinatal period or early childhood, and many of them become chronic carriers. Most children with chronic HBV infection are asymptomatic in spite of high levels of viremia, but run a long-term risk of developing liver cirrhosis or hepatocellular cancer later in life. HBV is not cytopathic, but the liver damage is considered to be caused by the immune response. Markers that identify children with a more severe prognosis are lacking. Further knowledge is also required about factors predicting and measuring response to interferon treatment. HBV vaccination is safe and effective but up to 10% of children born to HBeAg-positive mothers still become vertically infected in spite of immunoprophylaxis. It is not known if HBV DNA levels in these cases are particularly high, nor if or how pregnancy itself influences viremia levels.In an epidemiological study of children with chronic HBV living in Gothenburg, 93 children originating from 21 different countries were identified. Children from Asia were more often HBeAg positive, probably reflecting a higher proportion of vertically infected children. Fifty-four children were HBeAg positive and all but three had detectable HBV DNA by PCR. None of the children reported any symptom of hepatitis although nearly 40% had elevated aminotransferases. Only 3 out of 81 children had a previously diagnosed HBV infection when arriving in Sweden. Twelve children were born in Sweden to mothers of foreign origin; 11 of these had probably become infected vertically, in 3 cases in spite of immunoprophylaxis.Histological scoring was done in 71 children. Asian origin and presumed vertical transmission was associated with less liver damage. All HBeAg-negative children had low HBV DNA levels and mild or moderate liver inflammation. Precore mutations were found in nearly 50% of HBeAg-negative children, without association to HBV DNA level or liver damage. In HBeAg-positive carriers, a cytosine at position 1858 was associated with higher inflammation scores.Twenty-eight children were treated with interferon after priming with prednisolone. Both pretreatment and midtreatment HBV DNA levels were predictive of a sustained response. Seroconversion to anti-HBe and a viremia level < 1 million copies/mL was observed in 9 out of 28 children one year after the end of treatment.HBV DNA was analysed repeatedly in 55 pregnancies, showing values ranging from 108.1 to 109.5 copies/mL in 9 HBeAg-positive, and from undetectable (<100) to 106.8 copies/mL in 46 HBeAg-negative pregnancies. Post partum both viremia and ALT levels increased significantly. None of 243 HBeAg-negative pregnancies resulted in vertical transmission, but this had occurred, despite immune prophylaxis, in 3 out of 21 HBeAg-positive mothers, all of whom had very high HBV DNA levels (above 109.3 copies/mL).In summary, this study contributes to a better understanding of the epidemiology and pathogenesis of chronic hepatitis B in children in a low prevalence area. In addition, predictors for response to interferon therapy were identified, and the impact of pregnancy on viremia levels and inflammation, as well as the importance of viremia levels for vertical transmission of HBV, was demonstrated.