Author/Authors :
Kaya Ali نويسنده , Asan Ali نويسنده Department of Infectious Diseases and Clinical
Microbiology, Bursa Yuksek Ihtisas Training and Research Hospital,
Bursa, Turkey , Sayan Murat نويسنده Kocaeli University Faculty of Medicine, PCR Unit, Clinical
Laboratory, Kocaeli, Turkey , Akhan Sila نويسنده Department of Infectious Diseases and Clinical
Microbiology, Kocaeli University Faculty of Medicine, Kocaeli,
Turkey , Tekin Koruk Suda نويسنده Department of Infectious Diseases and Clinical
Microbiology, Koc University Faculty of Medicine, Istanbul,
Turkey , Aygen Bilgehan نويسنده Department of Infectious Diseases and Clinical
Microbiology, Erciyes University Faculty of Medicine, Kayseri,
Turkey , Sirmatel Fatma نويسنده Department of Infectious Diseases and Clinical
Microbiology, Abant Izzet Baysal University Faculty of Medicine,
Bolu, Turkey , Eraksoy Haluk نويسنده Department of Infectious Disease and Clinical
Microbiology, Istanbul Faculty of Medicine, Istanbul University,
Istanbul, Turkey , Tuna Nazan نويسنده Department of Infectious Diseases and Clinical
Microbiology, Sakarya University Faculty of Medicine, Sakarya,
Turkey , Köse Sukran نويسنده Department of Infectious Diseases and Clinical
Microbiology, Tepecik Training and Research Hospital, Izmir,
Turkey , Eren Tulek Necla نويسنده Department of Infectious Diseases and Clinical
Microbiology, Ankara Training and Research Hospital, Ankara,
Turkey , Aktug Demir Nazlim نويسنده Department of Infectious Diseases and Clinical
Microbiology, Selcuk University Faculty of Medicine, Konya,
Turkey , Mistik Resit نويسنده Department of Infectious Diseases and Clinical
Microbiology, Uludag University Faculty of Medicine, Bursa,
Turkey , Ormen Bahar نويسنده Department of Infectious Diseases and Clinical
Microbiology, Izmir Katip Celebi University Atatürk Training and
Research Hospital, Izmir, Turkey , Korkmaz Fatime نويسنده Department of Infectious Diseases and Clinical
Microbiology, Konya Training and Research Hospital, Konya,
Turkey , Yildirmak Taner نويسنده Department of Infectious Diseases and Clinical
Microbiology, Okmeydani Training and Research Hospital, Istanbul,
Turkey , Ural Onur نويسنده Department of Infectious Diseases and Clinical
Microbiology, Selcuk University Faculty of Medicine, Konya,
Turkey , Aydin Mehtap نويسنده Department of Infectious Disease and Clinical
Microbiology, Baskent University Faculty of Medicine, Istanbul,
Turkey , Turgut Huseyin نويسنده Department of Infectious Diseases and Clinical
Microbiology, Pamukkale University Faculty of Medicine, Denizli,
Turkey , Gunal Ozgur نويسنده Department of Infectious Diseases and Clinical
Microbiology, Samsun Training and Research Hospital, Samsun,
Abstract :
Background Hepatitis B virus (HBV) has a high mutation rate due to
its unusual replication strategy leading to the production of a large
number of virions with single and double mutations. The mutations, in
turn, are associated with the development of drug resistance to
nucleos(t)ide analogs (NUCs) in patients before and during NUCs therapy.
Objectives The current study aimed at investigating the molecular
characterization of HBV in Turkish patients with chronic hepatitis B
(CHB) infection. Methods Polymerase chain reaction (PCR) amplification
and direct sequencing procedures were used to analyze mutations. The
detected drug resistance mutations were divided into the nucleos(t)ide
analogs primary, partial, and compensatory resistance groups. The amino
acid substitutions of hepatitis B surface antigen (HBsAg) were
categorized into antiviral drug - associated potential vaccine - escape
mutations (ADAPVEMs) and typical HBsAg amino acid substitutions, which
included hepatitis B hyperimmunoglobulin (HBIg) - selected escape
mutation, vaccine escape mutation, hepatitis B misdiagnosis, and immune
- selected amino acid substitutions. Results The number of patients
included in the study was 528 out of which 271 (51.3%) were treatment -
naive and 351 (66.3%) were hepatitis B e antigen (HBeAg) - negative.
Moreover, 325 (61.6%) were males with a mean age of 38 years (range: 18
- 69). Primary, partial, and compensatory resistance to NUCs was
reported in 174 (32.9%) patients. Six different ADAPVEM motifs were
determined in both treatment - naive and treatment - experienced
patients, namely, sF161L/rtI169X, sE164D/rtV173L, sL172L/rtA181T,
sL173F/rtA181V, sS195M/rtM204V, and sS196L/rtM204I. The prevalence of
ADAPVEMs and typical HBsAg escape mutations was 5.3% (n = 28) and 34.8%
(n = 184), respectively. Conclusions The analysis of drug resistance
should constitute a fundamental part of the follow - up period of
patients with CHB undergone treatment with NUCs. The surveillance of
development of drug resistance mutations, while receiving treatment for
hepatitis B is of paramount importance to monitor and control the
emerging resistance.
