IDENTIFICATION OF HDAG-L VARIANTS IN COVERT HEPATITIS D AMONG AMERINDIANS OF ARGENTINA WITH MAINLY OCCULT INFECTIONS OF HBV

C.M. DELFINO, C. BERINI, M.E. EIRIN, R. MALAN, E. GENTILE, A. CASTILLO, W. PEDROZO, R. KRUPP, J. OUBIÑA, V. MATHET, M. BIGLIONE

Barcelona

Congreso; The International Liver Congress™ 2012; 2012

European Association for the Study of the Liver.

Background and aims. HDV is a defective virus that requires the helper function of HBV for its assembly and transmission. The HDV particle is composed of an outer envelope of HBV surface proteins, while the genomic RNA is associated with two isoforms of the delta antigen, HDAg-S and HDAg-L. This last plays an essential role interacting with HBsAg in the assembly of HDV virions. Guidelines suggest that all HBsAg-positive patients should be tested for anti-HDV IgG antibodies and confirmed by HDV RNA detection. The aim of this study was to determine the serological prevalence and molecular features of HDV within an Amerindian community of Argentina. Methods. Fourty-six Mbyá-Guaranies from a community located in the northern province of Misiones who were reactive for HBsAg and/or total anti-HBc were tested for HDV infection. All samples were tested for total anti-HDV by ELISA and concomitantly, a partial region coding for the HDAg was amplified by RT-nested-PCR. The positive samples were sequenced and translated into amino acid sequences of HDAg-S (aa110 to 198) and HDAg-L (aa 110 to 214) by Bioedit. Results. All samples resulted non-reactive by ELISA, but 3 were positive by RT-nPCR. These samples were anti-HBc positive only, of which 2 harbored HBV-DNA (genotypes F4 and A2), and therefore identified as cases of occult hepatitis B infection (OBI). The 3 cases were HBeAg negative and presented normal ALT/AST levels, being one of them reactive for anti-HBe. All sequences were ascribed to HDV genotype 1, but exhibited nucleotide differences in HDAg-L among which mutations at codons 197 and 201 have been described in vitro to promote an unsuitable interaction with HBsAg. Conclusions. These results provide evidence of covert HDV infection even among OBI cases. Recently, HDV infection has been described among Swiss chronic hepatitis B patients with undetectable HBsAg. This antecedent highlights the need to reevaluate the currently applied guidelines for HDV diagnostic algorithms; to investigate if the presence of HDV RNA in plasma correlates with any clinical marker of activity or stage of liver disease, as well as to explore if the observed mutations promote any effect on in vivo HDV pathogenesis.