Lamivudine dirençli kronik hepatit B'li hastalarda adefovir dipivoksilin etkinliği
Loading...
Date
2006
Authors
Kaya, Tezcan
Journal Title
Journal ISSN
Volume Title
Publisher
Uludağ Üniversitesi
Abstract
Kronik hepatit B (KHB) virus infeksiyonu dünyada tahmin edilen prevalansıyla 400 milyondan fazla kişide görülmektedir. KHB’si ve viral replikasyon bulguları olan hastalar ciddi karaciğer hastalığı yönünden yüksek risk altındadırlar. Lamivudin tedavisinin KHB’li hastalarda virolojik, biyokimyasal ve histolojik olarak etkili olduğu gösterilmiştir. Uzun dönem lamivudin tedavisiyle ilgili önemli bir sorun hepatit B virusu (HBV) polimerazında mutasyonlara bağlı viral direnç gelişimidir. Lamivudine dirençli HBV gelişmesi, lamivudine klinik ve virolojik cevabı azaltır. Bu nedenle lamivudine dirençli hastalarda alternatif veya ek tedaviler gereklidir. Adefovir dipivoksil lamivudine dirençli KHB’de etkili olduğu gösterilmiş bir nükleotid analogudur. Bu nedenle lamivudine dirençli KHB’li hastalarda genellikle adefovire geçilmesi önerilmektedir. Bu çalışmanın amacı bizim toplumumuzdaki lamivudine dirençli KHB’li hastalarda adefovir dipivoksilin etkinliğini değerlendirmekti. Çalışmaya lamivudine dirençli KHB’si olan 47 hasta alındı. Tüm hastalara en az 6 ay süreyle (aralık, 6–24 ay) 10mg/gün adefovir dipivoksil verildi. Başlangıçta ve tedavi boyunca her 3 ayda bir serum HBV-DNA, aspartat aminotransferaz (AST), alanin aminotarnsferaz (ALT) değerleri ölçüldü. Adefovir dipivoksil ile tedavinin 3, 6, 12, 18 ve 24. aylarındaki ortalama HBV-DNA, AST, ALT seviyelerinde başlangıçtaki ortalama değerlere göre anlamlı değişiklik saptandı (p<0,001). Adefovir dipivoksil alan hastalarda serum HBV-DNA, AST, ALT seviyeleri anlamlı olarak azaldı. Çalışmada adefovir dipivoksil, tedavi süresince genel olarak iyi tolere edildi. Bu çalışmada, daha önceki çalışmalara benzer şekilde adefovir dipivoksil lamivudine dirençli KHB’li hastalarda anlamlı antiviral ve biyokimyasal etki gösterdi. Lamivudine dirençli KHB’li hastalarda adefovir dipivoksilin uzun dönem etkinlik ve güvenirliğinin değerlendirilmesi için başka çalışmalar gerekmektedir.
Chronic hepatitis B (CHB) virus infection is common, with an estimated global prevalence of more than 400 million people. Patients with CHB and evidence of ongoing viral replication have a high risk of serious liver disease. Lamivudine has been shown to achieve virological, biochemical, and histological responses in patients with CHB. A major problem with prolonged lamivudine therapy is the increasing rate of viral resistance due to mutations within the hepatitis B virus (HBV) polymerase. Emergence of lamivudine resistant HBV has been associated with a diminished clinical and virologic response to lamivudine. Thus, there is a clear need for alternative or additional therapies against lamivudine resistant HBV. Adefovir dipivoxil is a nucleotide analog that has been shown to have activity against lamivudine resistant HBV. Therefore, a switch to adefovir is usually recommended for patients with lamivudine resistant CHB. The aim of this study was to evaluate the efficacy of adefovir dipivoxil against lamivudine resistant chronic hepatitis B in our patients. 47 patients with lamivudine resistant CHB were enrolled in the study. All patients received adefovir dipivoxil 10 mg once daily for at least 6 months (range, months 6–24). Serum HBV-DNA, aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels were measured at baseline and every 3 months during the treatment period. There were significant change in mean HBV-DNA, AST, ALT levels following 3,6,12,18,24 months of treatment with adefovir dipivoksil from baseline (p<0,001). Serum HBV-DNA, AST, ALT levels significantly decreased in patients receiving adefovir dipivoxil. Adefovir dipivoxil was generally well tolerated during treatment period in the study. In this study, as previous studies adefovir dipivoxil showed significant antiviral and biochemical activity in CHB patients with lamivudine resistance. Further studies are needed to examine long term efficacy and safety of adefovir dipivoxil in patients with lamivudine resistant CHB.
Chronic hepatitis B (CHB) virus infection is common, with an estimated global prevalence of more than 400 million people. Patients with CHB and evidence of ongoing viral replication have a high risk of serious liver disease. Lamivudine has been shown to achieve virological, biochemical, and histological responses in patients with CHB. A major problem with prolonged lamivudine therapy is the increasing rate of viral resistance due to mutations within the hepatitis B virus (HBV) polymerase. Emergence of lamivudine resistant HBV has been associated with a diminished clinical and virologic response to lamivudine. Thus, there is a clear need for alternative or additional therapies against lamivudine resistant HBV. Adefovir dipivoxil is a nucleotide analog that has been shown to have activity against lamivudine resistant HBV. Therefore, a switch to adefovir is usually recommended for patients with lamivudine resistant CHB. The aim of this study was to evaluate the efficacy of adefovir dipivoxil against lamivudine resistant chronic hepatitis B in our patients. 47 patients with lamivudine resistant CHB were enrolled in the study. All patients received adefovir dipivoxil 10 mg once daily for at least 6 months (range, months 6–24). Serum HBV-DNA, aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels were measured at baseline and every 3 months during the treatment period. There were significant change in mean HBV-DNA, AST, ALT levels following 3,6,12,18,24 months of treatment with adefovir dipivoksil from baseline (p<0,001). Serum HBV-DNA, AST, ALT levels significantly decreased in patients receiving adefovir dipivoxil. Adefovir dipivoxil was generally well tolerated during treatment period in the study. In this study, as previous studies adefovir dipivoxil showed significant antiviral and biochemical activity in CHB patients with lamivudine resistance. Further studies are needed to examine long term efficacy and safety of adefovir dipivoxil in patients with lamivudine resistant CHB.
Description
Keywords
Hepatit B, Adefovir, Lamivudin, Antiviral direnç, Hepatitis B, Lamivudine, Antiviral resistance
Citation
Kaya, T. (2006). Lamivudine dirençli kronik hepatit B'li hastalarda adefovir dipivoksilin etkinliği. Yayınlanmamış uzmanlık tezi. Uludağ Üniversitesi Tıp Fakültesi.