title: HDAg-L variants in covert hepatitis D and HBV occult infection among Amerindians of Argentina: new insights.
abstract: BACKGROUND
  Guidelines suggest that all HBsAg-positive patients should be tested for anti-HDV IgG antibodies and to confirm active hepatitis D virus (HDV) infection by detection of HDV RNA by reverse transcriptase (RT) polymerase chain reaction (PCR).
  
  
  OBJECTIVE
  The aim of this study was to determine the serological prevalence and molecular features of HDV within an Amerindian community from Argentina exhibiting positivity for HBsAg and/or anti-HBc total Ig.
  
  
  METHODS
  Forty-six plasma samples were tested for the detection of total anti-HDV antibodies by ELISA. Concomitantly, a partial RNA region coding for the delta antigen (HDAg) was amplified by RT-nested PCR (RT-nPCR). In silica translation of DNA sequences into the amino acid (aa) sequence of HDAg-S (aa110-195) and HDAg-L (aa110-214) was performed.
  
  
  RESULTS
  Out of 46 HDV non-reactive samples by ELISA, 3 were HDV RNA positive by RT-nPCR. These samples were anti-HBc-only positive, 2 of them identified as cases of occult hepatitis B infection (OBI). The 3 cases were HBeAg-negative and showed normal ALT/AST levels. All sequences were ascribed to HDV genotype 1, but exhibited nucleotide differences in HDAg-L coding region, among which, mutations at codons 197 and 201 - reportedly known to promote in vitro an unsuitable interaction with HBsAg - were observed.
  
  
  CONCLUSIONS
  These results provide evidence of covert HDV infection even among OBI, highlighting the need to reevaluate the currently applied guidelines for HDV diagnostic algorithms, as well as to explore if the observed mutations promote any effect on HDV pathogenesis.
authors.affiliation: Institute of Biomedical Research in Retroviruses and AIDS (INBIRS), University of Buenos Aires (UBA), Ciudad Autónoma de Buenos Aires, Argentina. cdelfino@fmed.uba.ar
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Delfino
authors.forename: María E
authors.initials: ME
authors.lastname: Eirin
authors.forename: Carolina
authors.initials: C
authors.lastname: Berini
authors.forename: Richard
authors.initials: R
authors.lastname: Malan
authors.forename: Emiliano
authors.initials: E
authors.lastname: Gentile
authors.forename: Amalia
authors.initials: A
authors.lastname: Castillo
authors.forename: Williams
authors.initials: W
authors.lastname: Pedrozo
authors.forename: Ramón
authors.initials: R
authors.lastname: Krupp
authors.forename: Jorgelina
authors.initials: J
authors.lastname: Blejer
authors.forename: José R
authors.initials: JR
authors.lastname: Oubiña
authors.forename: Verónica L
authors.initials: VL
authors.lastname: Mathet
authors.forename: Mirna M
authors.initials: MM
authors.lastname: Biglione
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001118:Argentina; D058070:Asymptomatic Diseases; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006508:Hepatitis Antibodies / Q000097:blood; D006509:Hepatitis B / Q000150:complications*; D003698:Hepatitis Delta Virus / Q000235:genetics*; D035923:Hepatitis delta Antigens / Q000097:blood* / Q000235:genetics*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007199:Indians, South American; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D016036:Seroepidemiologic Studies; D055815:Young Adult
chemical_list: D006508:Hepatitis Antibodies; D035923:Hepatitis delta Antigens; D007074:Immunoglobulin G; D012367:RNA, Viral