Detection of different viral strains of hepatitis B virus in chronically infected children after seroconversion from HBsAg to anti-HBs indicating viral persistence

Abstract

Background/aims: Seroconversion to anti-HBs or the loss of HBsAg is usually associated with complete elimination of the replicative hepatitis B virus. Usually in these patients hepatitis B virus DNA (HBV DNA) becomes undetectable. Routine controls of patients who underwent anti-HBs seroconversion by more sensitive tests showed that in some cases the virus persisted in the patient. Therefore the aim of our study was to evaluate if virus persistence could also be found in children with chronic hepatitis B after anti-HBs seroconversion. The virus pool should be characterized before and after seroconversion.

Methods: Viral DNA was extracted from nine HBsAg negative or anti-HBs positive sera of children, previously diagnosed as chronic HBsAg carriers. HBV DNA was amplified by polymerase chain reaction. Subsequently the nucleotide sequences of the polymerase chain reaction product in the a-determinant region (aa 121-161) were analyzed on an automatic fluorescent sequencer.

Results: In the sera of seven children, HBV DNA was detected in the HBsAg negative phase of the HBV infection. Mutations in codons 122, 125, 127, 131, 134, 143, 159 and 161 of the S gene could be documented, resulting in amino acid changes. In three patients the sequence analysis revealed changes in the HBV genotype from genotype A (serotype adw) to genotype D (serotype ayw) during seroconversion to anti-HBs.

Conclusions: These data demonstrate that persistence of the hepatitis B virus can also occur in HBsAg negative and anti-HBs positive children. After loss of HBsAg, no specific HBV variant was identified. Although a conclusive explanation for the selection process cannot be provided, it remains a fact that the 'surviving' viral strain was mostly represented by genotype D.