Kronik hepatit B enfeksiyonu olan hastalarda lamivudin tedavisi sırasında oluşan antiviral direnç mutasyonlarının araştırılması
Loading...
Files
Date
2012
Authors
Hoyrazlı, Ayşe
Journal Title
Journal ISSN
Volume Title
Publisher
Uludağ Üniversitesi
Abstract
Hepatit B virüsü (HBV) enfeksiyonu küresel bir halk sağlığı sorunudur. Tüm dünyada siroz ve hepatosellüler karsinomanın (HCC) önde gelen nedenidir. Dünyada en az 400 milyon kişinin HBV taşıyıcısı olduğu tahmin edilmektedir ve yılda 1 milyon kişi hepatit B ile ilişkili hastalıklar nedeniyle ölmektedir. Kronik hepatit B tedavisinde günümüzde; immünmodülatör, antiviral etkili pegile-interferonlar ve nükleozid analogları kullanılmaktadır. Nükleozid analogları arasında etkinliği yüksek, iyi tolere edilen, ciddi yan etkisi olmayan ve diğer ilaçlara göre daha ucuz olan lamivudin sık tercih edilen bir ilaçtır. Lamivudin, HBV replikasyonunu sağlayan ?revers transkriptaz (RT)? enzimini bloke ederek virüsün replike olmasını engellemektedir. Uzun dönem lamivudin tedavisiyle ilgili önemli bir sorun HBV polimerazında mutasyonlara bağlı viral direnç gelişimidir. Lamivudine dirençli HBV gelişmesi tedaviye klinik ve virolojik cevabı azaltır. Bu nedenle ilaç direnç gelişiminin hastada mümkün olduğunca erken tespit edilmesi tedavinin gidişatının değerlendirilmesinde önemlidir.Çalışmaya kronik hepatit B tanısıyla 6 aydan uzun süredir lamivudin tedavisi alan, izleminde virolojik kırılma saptanıp genotipik mutasyon analizi yapılan 33 hasta dahil edildi. Hastaların dosyaları geriye dönük olarak incelendi. 23 hastada genotipik olarak lamivudin direnci saptandı. Tedavi öncesi ALT düzeyi, HBV DNA düzeyi, HBeAg durumu, tedavi süresi ile lamivudin direnci arasındaki ilişki araştırıldı. Literatürden farklı olarak HBeAg negatif hastalarda daha fazla lamivudin direnci gözlendi (p=0,036). Mutasyon saptanan hastalarda tedavi öncesi HBV DNA düzeyi ve tedavi süresiyle (sınır süre 3 yıl) genotipik direnç arasında ilişki saptanmadı (p=0,733, p=0,682). Mutasyon kodonları incelendiğinde en fazla tek başına rtM204I (%21,2), daha sonra rtL180M ve rtM204V birlikteliği (%12,1) görüldü.
Hepatitis B virus (HBV) infection is a global public health problem. It is the leading cause of cirrhosis and hepatocellular carcinoma (HCC) worldwide. It is estimated there are at least 400 million HBV carriers in the world and that up to one million die annually due to hepatitis B associated liver disease. Pegylated-interferons with immunomodulatory, antiviral effects and nucleoside analogs are used today for treatment of chronic hepatitis B. Among the nucleoside analogs, lamivudine is frequently the drug of choice because of its high efficacy, good tolerability, low rate of adverse effects and low cost compared with other drugs. Lamivudine, blocks HBV replication providing enzyme, reverse transcriptase (RT) and prevents viral replication. A major problem with prolonged lamivudine therapy is the increasing rate of viral resistance due to mutations within the HBV polymerase. Emergence of lamivudine resistant HBV has been associated with a diminished clinical and virologic response to lamivudine. Therefore, detection of antiviral resistance in patients as early as possible is important to manage treatment appropriatelly.In this study, 33 chronic hepatitis B patients with virologic breakout who was treated with lamivudin for more than 6 months and underwent genotypic mutation analysis were included. Patients were evaluated retrospectively. Genotypic lamivudine resistance was detected in 23 patients. The relationship between the with lamivudine resistance and pre-treatment ALT level, HBV DNA level, HBeAg status, duration of treatment were examined. We observed more mutations in HBeAg negative lamivudine resistant patients apart from the literature (p=0,036). Pre-treatment HBV DNA level and duration of treatment ( cut-off time= 3 years) were unrelated with genotypic resistance in mutant group (p=0,733, p=0,682). Most common mutations rtM204I (%21,2) and rtL180M with rtM204V combination (%12,1) were observed in mutation analysis of codons.
Hepatitis B virus (HBV) infection is a global public health problem. It is the leading cause of cirrhosis and hepatocellular carcinoma (HCC) worldwide. It is estimated there are at least 400 million HBV carriers in the world and that up to one million die annually due to hepatitis B associated liver disease. Pegylated-interferons with immunomodulatory, antiviral effects and nucleoside analogs are used today for treatment of chronic hepatitis B. Among the nucleoside analogs, lamivudine is frequently the drug of choice because of its high efficacy, good tolerability, low rate of adverse effects and low cost compared with other drugs. Lamivudine, blocks HBV replication providing enzyme, reverse transcriptase (RT) and prevents viral replication. A major problem with prolonged lamivudine therapy is the increasing rate of viral resistance due to mutations within the HBV polymerase. Emergence of lamivudine resistant HBV has been associated with a diminished clinical and virologic response to lamivudine. Therefore, detection of antiviral resistance in patients as early as possible is important to manage treatment appropriatelly.In this study, 33 chronic hepatitis B patients with virologic breakout who was treated with lamivudin for more than 6 months and underwent genotypic mutation analysis were included. Patients were evaluated retrospectively. Genotypic lamivudine resistance was detected in 23 patients. The relationship between the with lamivudine resistance and pre-treatment ALT level, HBV DNA level, HBeAg status, duration of treatment were examined. We observed more mutations in HBeAg negative lamivudine resistant patients apart from the literature (p=0,036). Pre-treatment HBV DNA level and duration of treatment ( cut-off time= 3 years) were unrelated with genotypic resistance in mutant group (p=0,733, p=0,682). Most common mutations rtM204I (%21,2) and rtL180M with rtM204V combination (%12,1) were observed in mutation analysis of codons.
Description
Keywords
Kronik hepatit B, Lamivudin, Antiviral direnç, Chronic hepatitis B, Lamivudine, Antiviral resistance
Citation
Hoyrazlı, A. (2012). Kronik hepatit B enfeksiyonu olan hastalarda lamivudin tedavisi sırasında oluşan antiviral direnç mutasyonlarının araştırılması. Yayınlanmamış uzmanlık tezi. Uludağ Üniversitesi Tıp Fakültesi.