Treatment for hepatitis B in patients with drug resistance

Tacke, Frank; Kroy, Daniela C.

doi:10.21037/atm.2016.09.19

Cited by 31 publications

(29 citation statements)

References 36 publications

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“…In vitro, this rtA194T polymerase mutation is associated with partial drug resistance against TDF. On the other hand, the rtA194T mutation reduces susceptibility to TDF and impairs viral replication capacity of HBV constructs in vitro, possibly explaining the low occurrence of this mutant form in clinical practice [11][12][13] .…”

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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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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“…Bu çalışmada, bir yıl süre ile LAM kullanmış 50 hastanın 12'sinde (%24) LAM direncine neden olan mutasyonların varlığı belirlenmiştir. Yapılan çalışmalarda, LAM dirençli suş oranları ve direnç tipleri farklılık göstermektedir (8)(9)(10)(17)(18)(19)(20)(21) .…”

Section: Discussionunclassified

“…Lamivudin tedavisi alan hastalarda YMDD mutasyon oranları tedavinin birinci yılında yaklaşık %23 iken, tedavinin 4-5. yıllarından sonraki oranlar ise %70-80'leri bulmaktadır (10) . Mutasyonların erken belirlenmesi, klinik deği-şiklikleri anlamak ve tedavi değişikliklerini hız-landırmak için gereklidir (11) .…”

Section: Introductionunclassified

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

Kırdar¹,

Yaşa²,

Aydın³

et al. 2016

TMCD

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“…Interestingly, the double mutants of L180M/M204V of LMV produce much higher viral loads than the single mutant M240I. It reflects the double point mutation accelerates the viral replication better than the single point mutation; this is probably due to the stabilizing effect of L180M mutation (B domain) on the YMDD loop (C domain) in a conformational model of the HBV reverse transcriptase …”

Section: The Current Development and Treatment For Chronic Hepatitis mentioning

confidence: 99%

2′‐Fluoro‐6′‐methylene carbocyclic adenosine and its phosphoramidate prodrug: A novel anti‐HBV agent, active against drug‐resistant HBV mutants

Singh

Mulamoottil

Chu

2018

Medicinal Research Reviews

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Chronic hepatitis B (CHB) is one of the major causes of morbidity and mortality worldwide. Currently, clinically approved nucleos(t)ide analogs (NAs) are very efficient in reducing the load of hepatitis B virus (HBV) with minimum side effects. However, the long-term administration of antiviral drugs promotes HBV for potential drug resistance. To overcome this problem, combination therapies are administered, but HBV progressively altered mutations remain a threat. Therefore, optimally designed NAs are urgently needed to treat drug-resistant HBV. Herein, 2'-fluoro-6'-methylene carbocyclic adenosine (FMCA) and its phosphoramidate (FMCAP) have been discovered, which may be utilized in combination therapies for curing drug-resistant chronic hepatitis B. In preclinical studies, these carbocyclic NAs demonstrated potential anti-HBV activity against adefovir, as well as lamivudine (LMV/LAM) drug-resistant mutants. In vitro, these molecules have demonstrated significant activity against LMV/entecavir (ETV) triple mutants (L180M + S202G + M204V). Also, preliminary studies of FMCA/FMCAP in chimeric mice and female Non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mouse models having the LMV/ETV triple mutant have shown a high rate of reduction of HBV DNA levels compared to ETV. In this review, we have summarized preclinical studies of FMCA and its phosphoramidate prodrug (FMCAP).

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Treatment for hepatitis B in patients with drug resistance

Cited by 31 publications

References 36 publications

Detection of Hepatitis B Virus Drug Resistance Mutations by Pyrosequencing Method

Detection of Hepatitis B Virus Drug Resistance Mutations by Pyrosequencing Method

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

2′‐Fluoro‐6′‐methylene carbocyclic adenosine and its phosphoramidate prodrug: A novel anti‐HBV agent, active against drug‐resistant HBV mutants

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