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

Sayan, Murat; Şentürk, Ömer; Akhan, Sıla; Hülagü, Sadettin; Çekmen, Mustafa

doi:10.1016/j.ijid.2009.11.039

Cited by 40 publications

(59 citation statements)

References 46 publications

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“…Several previous studies identified typical HBsAg amino acid substitutions are sP120T, sM133I, sS143L, sD144A/E, sG145R, sE164D, sW172*, and sW182* which is the most commonly occurring pattern (9,15,16). Vaccine escape/HBIg-selected escape mutants, sG145R and sP120T, in combination with LAM-associated resistance mutations, are often seen in HBV mono-infected patients after LAM or HBIg treatment (31).…”

Section: Discussionmentioning

confidence: 96%

“…Although most patients were identified to be hepatitis B e-antibody-positive asymptomatic carriers, they were found to be older in age with low hepatitis B e-antigen positivity, low alanine aminotransferase level, and low HBV DNA levels (Table 1). Our previous reports established that the frequencies of naturally occurring primary and compensatory mutations are very high in treatmentnaive HD patients when compared to treatment-naive CHB patients with normal renal function (15,23). However, clinical manifestation and the number of viral genomic substitutions in HBV carriers may be influenced by aging under long-term pressure from the host immune system.…”

Section: Discussionmentioning

confidence: 99%

“…for amplifying the HBV pol gene region ( pol gene sequence was employed for HBV genotyping and genotypic resistance analysis to NUCs as a part of routine investigations in our clinical laboratory). The PCR conditions were applied as previously described (15). (8).…”

Section: Methodsmentioning

confidence: 99%

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Naturally Occurring Polymerase and Surface Gene Variants of Hepatitis B Virus in Turkish Hemodialysis Patients with Chronic Hepatitis B

2012

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SUMMARY:The aim of this study was to assess the frequencies and patterns of naturally occurring genotypic resistance to nucleos(t)ide analogues (NUCs) and typical hepatitis B surface antigen (HBsAg) amino acid substitutions in naive hemodialysis (HD) patients with chronic hepatitis B. In order to achieve this, the genotypic resistance to NUCs and HBsAg amino acid substitutions were classified into primary/compensatory resistance mutation and antiviral drug-associated potential vaccine-escape mutation (ADAPVEM)/typical HBsAg amino acid substitution, respectively. Direct sequencing of polymerase ( pol) gene of hepatitis B virus (HBV) was performed on DNA samples obtained from 248 HBsAg-positive Turkish patients. Overall, 38z (n ＝ 94) of HBsAg-positive HD patients had detectable HBV DNA in their serum. Naturally occurring primary and compensatory resistance mutations to NUCs were detected in 30z (n ＝ 28) and 52z (n ＝ 49) of HD patients, respectively. However, 6 types of ADAPVEMs and 48 types of typical HBsAg amino acid substitutions were found in 10.6z (n ＝ 10) and 46z (n ＝ 43) of the HD patients, respectively. Our study suggests that every HD patient diagnosed with chronic hepatitis B, who is a potential candidate for NUCs treatment, should also be monitored for the baseline pol gene sequence changes before the initial treatment, for a more effective management of future treatment options. Further, a relatively higher frequency of ADAPVEMs variants needs to be addressed as a public health problem.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

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Naturally Occurring Polymerase and Surface Gene Variants of Hepatitis B Virus in Turkish Hemodialysis Patients with Chronic Hepatitis B

2012

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“…LAM ve LdT kullanımının yaygın ya da zorunlu olduğu popülasyonlarda (ülke-mizde bir süre öncesine kadar geçerli olan SUT'a göre KHB'li hastalarda HBV DNA düzeyi <10 7 İÜ/ml ise NA tedavisi yalnız LAM ya da LdT ile başlatılabilmekteydi) primer ve kompansatuar ilaç direnci mutasyonları sıklıkla saptanmaktadır (153)(154)(155)(156). KHB'li hastaların NA tedavilerinde ortaya çıkabilen primer ve kompansatuar ilaç direnci mutasyonları ve S geninde yol açtıkları aminoasid değişiklikleri Tablo 5'te görülmektedir.…”

Section: Nükleoz(t)id Analoglarına Karşı Viral Direnç Ve Direncin İzlemiunclassified

“…HBV pol geninde NA hedef bölgesinde meydana gelen kompansatuar mutasyonlar, KHB'li hastaların tedavilerinde gereksiz ya da hatalı ilaç değişiklikleri yapılmasına yol açmaktadır. Hem NA naif hem de LAM ve/veya ADV tedavisi alan KHB hastalarında rtQ215H/Q/P/S kompansatuar mutasyonları sık saptanmaktadır (153)(154)(155)(156)(157). Bu nedenle NA tedavilerinde yapılacak ilaç değişikliklerinde ve rasyonel bir NA yönetiminde HBV ilaç direnci analizleri yapılması önemlidir.…”

Section: Nükleoz(t)id Analoglarına Karşı Viral Direnç Ve Direncin İzlemiunclassified

Management of Chronic Hepatitis B Virus Infection: A Consensus Report of the Study Group for Viral Hepatitis of the Turkish Society of Clinical Microbiology and Infectious Diseases

Akhan¹,

Aynıoğlu²,

Çağatay³

et al. 2015

Klimik Dergisi

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ÖzetTürk Klinik Mikrobiyoloji ve İnfeksiyon Hastalıkları Derneği Viral Hepatit Çalışma Grubu, dünyada 400 milyonun üzerinde kişide bulunan kronik hepatit B virusu (HBV) infeksiyonunun yönetimi-ne ilişkin bir uzlaşı raporu hazırlamak üzere bir toplantı düzenle-miştir. Raporda konuyla ilgili literatür ve uluslararası kılavuzlar, hepatit B virusu (HBV) infeksiyonunun epidemiyolojisi ve doğal seyri, kronik hepatit B (KHB)'nin ülke ekonomisine maliyeti, akut hepatit B (AHB) ve KHB'de tanı, AHB'nin KHB akut alevlenmesinden ayırt edilmesi, KHB tedavisi, HBeAg-pozitif ve negatif hastalarda tedaviye yanıtın değerlendirilmesi ve uzun dönem sonuçları, nükleoz(t)id analoglarına karşı viral direnç ve direncin izlemi ve hepatit B'den korunma gibi bölümler halinde gözden geçirilmiş ve üzerinde uzlaşılan öneriler her bölümün sonunda sunulmuştur. Bu önerilerden seçilmiş birkaçı aşağıda sıralan-mıştır: [1] İlk basamak tedavisi olarak entekavir ya da tenofovir gibi dirence karşı genetik bariyeri yüksek çok güçlü ilaçların seçilmesi, uzun süreli tedavi hedeflerine ulaşmak için en uygun AbstractStudy Group for Viral Hepatitis of the Turkish Society of Clinical Microbiology and Infectious Diseases convened a meeting to develop a consensus report on management of chronic hepatitis B virus (HBV) infection, a global public health problem, affecting more than 400 million people worldwide. Relevant literature and international guidelines were reviewed, and recommendations agreed are presented at the end of each section such as epidemiology and natural history of HBV infection, economic burden of chronic hepatitis B (CHB), diagnosis of acute hepatitis B (AHB) and CHB, differentiation of AHB from acute exacerbation of CHB, treatment of CHB, evaluation of response to treatment and longterm outcomes in HBeAg-positive and negative patients, antiviral resistance and its follow-up, and prevention of HBV infection. Examples of some selected recommendations are as follows: [1] The selection of a highly potent drug such as entecavir or tenofovir with a high genetic barrier to resistance as a first line therapy provides the best approach of achieving the goals of long-term

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Lamivudine resistance mutations in European patients with hepatitis B and patients co‐infected with HIV and hepatitis B

Taramasso

Caligiuri

Biagio

et al. 2011

Journal of Medical Virology

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Evaluation of resistance pattern in patients with chronic hepatitis B. Retrospective study of hepatitis B virus (HBV) resistance mutations in patients found viraemic after first-line treatment. HBV viral load was determined by a real-time polymerase chain reaction and the substitutions in HBV-DNA were studied by polymerase sequencing test. First line treatment had failed in 12 out of 33 patients (36%) receiving anti-HBV drugs. The 12 patients with persistent viraemia were all lamivudine (LAM) experienced and 7 had a polymerase sequencing test available. LAM substitution mutations L180M + M204V/I were found in six out of seven cases, with an accompanying V173L mutation in three cases. These mutations were also related with changes in HBsAg. The use of potent drugs in the first line anti-HBV therapy may reduce the resistance mutations in the future.

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

Abstract: 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.

Cited by 40 publications

References 46 publications

Naturally Occurring Polymerase and Surface Gene Variants of Hepatitis B Virus in Turkish Hemodialysis Patients with Chronic Hepatitis B

Naturally Occurring Polymerase and Surface Gene Variants of Hepatitis B Virus in Turkish Hemodialysis Patients with Chronic Hepatitis B

Management of Chronic Hepatitis B Virus Infection: A Consensus Report of the Study Group for Viral Hepatitis of the Turkish Society of Clinical Microbiology and Infectious Diseases

Lamivudine resistance mutations in European patients with hepatitis B and patients co‐infected with HIV and hepatitis B

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