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Detection of a hepatitis B surface antigen variant emerging in a patient with chronic lymphocytic leukaemia treated with fludarabine
Author(s) -
Alexopoulou Alexandra,
Dourakis Spyros P.,
Pandelidaki Helen,
Archimandritis Athanasios J.,
Karayiannis Peter
Publication year - 2006
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.20660
Subject(s) - hbsag , virology , fludarabine , hepatitis b virus , orthohepadnavirus , biology , hepatitis b , hepadnaviridae , medicine , virus , immunology , genetics , chemotherapy , cyclophosphamide
Fludarabine is used widely for the treatment of chronic lymphocytic leukaemia, but not as yet implicated in the emergence of hepatitis B surface antigen (HBsAg) variants following hepatitis B virus (HBV) reactivation. Such a variant was detected in a 78‐year‐old female who was HBsAg(−)/anti‐HBc(+)/anti‐HBs(+)/anti‐HBe(+), and with normal ALT levels, who developed HBV reactivation after fludarabine treatment. She had high HBV‐DNA levels, and became positive for HBeAg, in the absence of detectable HBsAg. HBV‐DNA was extracted from serum and the HBsAg encoding region of the genome was amplified by PCR, followed by cloning and sequencing. The HBV strain appeared to be subtype adw , but had higher nucleotide homology with ayw than adw isolates, supported further by phylogenetic tree analysis. Amino‐acid sequence comparisons over the α determinant region revealed the following substitutions: C124N, G130R, and N146S. There were also unique substitutions outside the α determinant. All these mutations appeared to have a profound effect on the antigenicity of this region, which resulted in failure to detect HBsAg by commercially available diagnostic assays. It is concluded that a surface variant emerged in an HBsAg(−)/anti‐HBs(+) patient with chronic lymphocytic leukaemia following fludarabine treatment, with an unprecedented number of amino‐acid substitutions in the α determinant region of HBsAg, including a subtype switch. J. Med. Virol. 78:1043–1046, 2006. © 2006 Wiley‐Liss, Inc.