Monitoring of hepatitis B virus surface antigen escape mutations and concomitantly nucleos(t)ide analog resistance mutations in Turkish patients with chronic hepatitis B.
BACKGROUND
The hepatitis B virus (HBV) polymerase gene completely overlaps with the envelope gene. In the present study we aimed to monitor the prevalence and pattern of the typical mutations for hepatitis B surface antigen (HBsAg) escape, and concomitantly nucleos(t)ide analog (NUC) resistance mutations, in Turkish patients undergoing different antiviral therapies and in treatment-naïve patients with chronic hepatitis B (CHB).


METHODS
The investigation was undertaken between March 2007 and August 2009 and involved a total of 142 patients under NUC therapy (88 males; mean age 42 years (range 13-68); hepatitis B e antigen (HBeAg) negativity in 94 patients; HBV DNA median log 4.3 log(10) IU/ml (range 2.0->6.0); alanine aminotransferase (ALT) median level 76.1 IU/ml (range 12-1082)) and 185 treatment-naïve CHB patients (120 males; mean age 39 years (range 1-76 years); HBeAg negativity in 132 patients; HBV DNA median log 3.5 log(10) IU/ml (range 2.0-6.0); ALT median level 60.7 IU/l (range 8-874)).


RESULTS
The overall prevalence of typical HBsAg escape mutations found in the CHB patients was 8.3% (27/327). In the NUC therapy group the prevalence was 8.5% (12/142), with the following patterns: sY100C+sI110V, sL109I, sP120T, sP127T, sG130R+sG145X, sS132A+sY134N, sY134N+sG145R, sC137G, sD144E, sG145R. In the treatment-naïve group the prevalence was 8.1% (15/185), with the following patterns: sL109I, sI110V, sS117INST, sP120T, sP127T, sM133I, sC137L+sG145R, sS143L. However, NUC resistance mutations were found in 7.7% (11/142) of the patients on NUC therapy and 3.8% (7/185) of the treatment-naïve group patients. Interestingly, the treatment-naïve patients had preexisting drug resistance mutations related to lamivudine (rtL180M+rtM204I), adefovir (rtA181V, rtQ215S, rtI233V), entecavir (intermediate susceptibility with rtL180M+rtM204IHBV variant), telbivudine (rtL180M+rtM204I), and tenofovir (rtA194T).


CONCLUSIONS
The findings of this study show preexisting typical HBsAg escape and NUC resistance mutations are possible. The genetic arrangement of the HBV genome with polymerase and surface genes overlapping has substantial public health and diagnostic implications and relevance.
Sayan
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Clinical Laboratory, PCR Unit, Faculty of Medicine, University of Kocaeli, İzmit-Kocaeli, Turkey. sayanmurat@hotmail.com
Sentürk
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Akhan
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Hülagü
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Cekmen
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D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D015684:Gene Products, pol / Q000235:genetics; D005814:Genes, Viral; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009705:Nucleosides / Q000494:pharmacology; D009711:Nucleotides / Q000494:pharmacology; D014421:Turkey; D055815:Young Adult
D004279:DNA, Viral; D015684:Gene Products, pol; D006514:Hepatitis B Surface Antigens; D009705:Nucleosides; D009711:Nucleotides; C066027:P protein, Hepatitis B virus