Monitoring of hepatitis B virus surface antigen escape mutations and concomitantly nucleos(t)ide analog resistance mutations in Turkish patients with chronic hepatitis B

作者：Sayan M^*; Senturk O; Akhan S C; Hulagu S; Cekmen M B

来源：International Journal of Infectious Diseases, 2010, 14: E136-E141.

DOI：10.1016/j.ijid.2009.11.039

• Hepatitis B virus
• HBsAg escape mutation
• Nucleos(t)ide analogs
• Drug resistance

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-naive 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-naive 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-naive 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-naive group patients. Interestingly, the treatment-naive 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.

• 出版日期2010-9