Detection of Resistance Mutations in Chronic Hepatitis B Patients Receiving Lamivudine Therapy Using Molecular Method

Kırdar, Sevin; Yaşa, Mehmet Hadi; Aydın, Neriman; Korkmazgil, Berna

doi:10.5222/tmcd.2016.135

Cited by 2 publications

(1 citation statement)

References 17 publications

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“…While rtM204I substitution may be detected alone, rtM204V/S may be seen together with other mutations [4] . He et al [23] determined the frequency of rtM204I to be 71.88% and Wen et al [24] as 29.2%, whereas in Turkey the rates of isolated rtM204I were reported as 12% by Kırdar et al [25] , 9% by Timur et al [8] , 5.8% by Aydoğan et al [26] , 6.4% by Bozdayi et al [27] , and 1.5% by Saran et al [28] .…”

Section: Discussionmentioning

confidence: 99%

Detection of Hepatitis B Virus Drug Resistance Mutations by Pyrosequencing Method

Çimentepe¹,

Yıldırım²,

Kömür³

et al. 2019

mjima

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Giriş: Kronik hepatit B virüs (HBV) enfeksiyonun uzun süreli tedavisi sırasında nükleoz(t)id analoglarına karşı ilaç direnci mutasyonlarının gelişmesi tedavi başarısızlığına yol açabilen önemli bir sorundur. Bu çalışmanın amacı kronik hepatit B enfeksiyonu olan hastalarda HBV ilaç direnci gen mutasyonlarının pyrosequencing metodu ile araştırılmasıdır. Gereç ve Yöntem: Kasım 2013 ve Mayıs 2014 tarihleri arasında, kronik hepatit B enfeksiyonu olan 89'u tedavi almayan (naif) ve 48'i tedavi alan toplam 137 hastaya ait serum örnekleri lamivudin (LAM), adefovir, telbivudin (TEL), entekavir (ETV) ve tenofovir (TDF) ile ilişkili ilaç direnç mutasyonlarının tespiti için real-time polimeraz zincir reaksiyonu testi sonrası pyrosequencing metodu (PyroStar HBV Drug Resistance Test, Altona Diagnostics, Germany) ile analiz edilmiştir. Bulgular: Tedavi almayan 89 hastada, TDF'ye duyarlılığı azaltan rtA194T mutasyonu bir (%1,1) olguda bulunmuştur. Tedavi edilen 48 hastada, LAM ve TEL'e ilaç direnci ve ETV'ye karşı da çapraz dirence sebep olan rtM204I mutasyonu bir (%2,1) olguda tespit edilmiştir. Kompansatuvar mutasyon olan rtL180M iki (%4,2) hastada gözlenmiştir. ETV direncini gösteren rtT184S mutasyonu ile birlikte rtM204V'nin varlığı bir (%2,1) hastada tespit edilmiştir. ÖzIntroduction: The development of drug resistance mutations to nucleos(t)ide analogues during long-term therapy for chronic hepatitis B virus (HBV) infection is a major problem that may lead to treatment failure. The aim of this study was to investigate the HBV drug resistance gene mutations in patients with chronic HBV infection by pyrosequencing method. Materials and Methods: Between December 2013 and May 2014, serum samples collected from 137 patients with chronic HBV infection, (89 treatment-naive and 48 treatment-experienced), were analyzed with real-time polymerase chain reaction analysis followed by pyrosequencing (PyroStar HBV Drug Resistance Test, Altona Diagnostics, Germany) for drug resistance mutations associated with lamivudine (LAM), adefovir, telbivudine (TEL), entecavir (ETV), and tenofovir (TDF). Results: Of the 89 treatment-naive patients, one (1.1%) had the rtA194T mutation, associated with reduced susceptibility to TDF. Of the 48 treatment-experienced patients, one (2.1%) had the rtM204I mutation, associated with drug resistance to LAM, TEL, and cross-resistance to ETV. Compensatory mutation rtL180M was observed in two patients (4.2%). The presence of rtM204V combined with rtT184S mutation indicating ETV resistance was detected in one patient (2.1%). Conclusion: The incidence of drug resistance mutations was 8.3% in treatment-experienced and 1.1% in treatment-naive patients. The use of pyrosequencing technology before and during treatment of patients with chronic HBV infection would contribute to the rapid detection of drug resistance mutations. Abstract Mehmet

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