Retrospective characterization of the S open reading frame of HBV isolated from children with membranous nephropathy treated with interferon-alpha2b.

BACKGROUND

A causal relationship exists between HBV infection and membranous nephropathy. The association is especially close in Black children in sub-Saharan Africa. Interferon-alpha2b is commonly used to treat this condition, but is effective in only 30-40% of patients. The reason for the poor response is unknown. The objective of this study was to determine if mutations in the surface gene of HBV isolated from Black children with HBV-associated membranous nephropathy before, during and after interferon treatment, have any effect on treatment response and vice versa.

METHODS

HBV DNA was extracted from a responder, a reverter and a non-responder before and after initiation of 16 weeks of interferon-alpha2b treatment. The preS1/preS2/S region was amplified, cloned and sequenced.

RESULTS

The preS2 region was the most variable in the reverter and the non-responder, and the S region was the most variable in the non-responder. Phylogenetic analysis showed that the viral population dynamics between the responder and the reverter/non-responder strains differed as a result of mutations in the surface gene.

CONCLUSIONS

The presence of mutations in the S region of HBV could be used as predictive markers to differentiate interferon-alpha2b responders from non-responders provided that detailed analysis of further genomes confirms our findings.