Histologic activity of childhood chronic hepatitis B related to viremia levels, genotypes, mutations, and epidemiologic factors.
BACKGROUND
Despite high viral load, children with chronic hepatitis B virus (HBV) infection may lack significant biochemical signs of liver dysfunction. Failure to develop abnormal liver chemistriesis is probably due to immunologic hyporeactivity. Despite the absence of biochemical abnormalities in these patients, there is still a risk for long-term complications. The pathogenic importance of viral load and genetic variability is less well studied in children than in adults.


METHODS
We evaluated viremia levels, genotypes, and mutations related to histologic evidence of liver damage in 71 HBV carriers, aged 2 to 18 years, all of non-Swedish origin.


RESULTS
None of the of 22 children who were hepatitis B e antigen (HBeAg) negative had severe liver disease or had HBV DNA levels greater than 10 copies/mL (mean 10 ); 3 (14%) of them had increased alanine aminotransferase (ALT). The 49 HBeAg-positive children had a mean HBV DNA level of 10 copies/mL, and increased ALT was seen in 28 (55%). Core promoter mutations (at nt 1764) or precore mutations (at codon 1, 2, or 28) were rare; they were seen in four and one HBeAg-positive children, and in four and nine HBeAg-negative children, respectively, without association to liver damage. C-1858 was associated with more liver inflammation. Genotype did not significantly influence liver damage. Children with horizontal transmission had a faster rate of seroconversion and more inflammation of the liver.


CONCLUSIONS
Severe HBeAg-negative hepatitis with high HBV DNA levels and mutations in the core promoter or precore regions seems to be less common in children than in adults. C-1858 strains may be more pathogenic, but this requires further study. Epidemiologic factors influence the course of infection.
Söderström
Ann
A
Department of Infectious Diseases, Göteborg University, Sweden. ann.soderstrom@medfak.gu.se
Norkrans
Gunnar
G
Conradi
Nils
N
Krantz
Marie
M
Horal
Peter
P
Lindh
Magnus
M
D000293:Adolescent; D000410:Alanine Transaminase / Q000097:blood; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005838:Genotype; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D006801:Humans; D008099:Liver / Q000473:pathology*; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D019562:Viral Load; D014766:Viremia / Q000235:genetics / Q000276:immunology / Q000473:pathology*
D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D000410:Alanine Transaminase