Kronik hepatit B'li hastalarda demografik özelikler, antiviral tedavi ve tedaviye yanıtın karşılaştırılması
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Date
2014
Authors
Yıldırım, Diğdem Özer
Journal Title
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Publisher
Uludağ Üniversitesi
Abstract
Hepatit B hastalığı dünya genelinde kronik karaciğer hastalığının en fazla görülen sebebidir ve hepatosellüler karsinom, siroz ve karaciğer yetmezliğine sebep olabilir. Antiviral tedavilerin amacı hastalığın progresyonunu önlemektir. Bunu da viral yükü ve fibrozisi azaltmakla yaparlar. Tedavi için interferon, nükleosid (lamivudine, entecavir, tenofovir) ve nükleotid analoglarını (adefovir, tenofovir) içeren çeşitli tedavi seçenekleri bulunmaktadır. Bu seçenekler HBV DNA düzeyleri, ALT, karaciğer histolojisi, HBeAg ve HBsAg üzerine değişik etkiler göstermekte ve farklı hasta gruplarında farklı düzeylerde tedavi yanıtı oluşturmaktadır. Bu çalışma kronik hepatit B nedeniyle en az bir yıldır tedavi alan hastaların demografik özellikleri, aldıkları tedaviler ve süreleri, tedavi değişiklikleri, yan etki profilleri, moleküler, serolojik, biyokimyasal ve histolojik özellikleri karşılaştırılarak tedavi grupları arasındaki benzer ve farklı özelliklerin belirlenmesi amacıyla yapılmıştır. Çalışmaya Uludağ Üniversitesi Tıp Fakültesi Hastanesi Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı Polikliniği'ne 01.01.2005-31.12.2012 tarihleri arasında başvurup kronik hepatit B nedeniyle tedavi alan 134 hasta dahil edildi. 22 hastanın interferon (%16,4), 48 hastanın lamivudin (%35,8), 45 hastanın entekavir (%33,5), 10 hastanın tenofovir (%7,4), 5 hastanın telbivudin (%3,7), 1 hastanın adefovir, 1 hastanın lamivudin+adefovir, 1 hastanın inteferon+entekavir ve 1 hastanın tenofovir+entekavir tedavisi aldıkları saptandı. İnterferon tedavisi alan hastaların ortalama tedavi süresi 8,7 ay; lamivudin alanların 34,6 ay; entekavir kullananların 36,5 ay; tenofovir alanların 37,8 ay; telbivudin grubunun ise 13 ay bulundu. Adefovir tedavisi alan hasta sayımız az olduğundan ortalama tedavi süresi değerlendirmesi yapılmadı. İnterferon alan 22 hastanın 12'sinde (%54), lamivudin alan 48 hastanın 15'inde (%31,2), entekavir alan 45 hastanın 6'sında (%13), telbivudin alan 5 hastanın 1'inde (%20), adefovir alan 1 hastada ve lamivudin+adefovir alan 1 hastada tedavi değişikliği yapıldığı gözlendi. Tenofovir tedavisi alan hastaların hiçbirinde tedavi değişikliği yapılmadığı saptandı. Tedavinin 1. yılında HBV DNA negatifleşmesi açısından lamivudin ile interferon ve lamivudin ile entekavir arasında istatistiksel fark saptanırken (sırasıyla p<0,026 ve p<0,05); lamivudin ile tenofovir tedavisi arasında istatistiksel fark gözlenmedi (p=0,356). Tedaviye direnç açısından tenofovir alan hastalarımızda direnç saptanmazken lamivudin alan hastalarda çeşitli çalışma sonuçlarına göre daha düşük (48 hastanın 15'inde (%31,2)), entekavir alan hastalarımızda daha yüksek (45 hastanın 5'inde (11,1)) direnç oranları görüldü. İlaç yan etkileri açısından değerlendirildiğinde entekavir kesilerek tenofovire geçilen 1 hastada osteopeni, 1 hastada fosfor düşüklüğü ve kreatinin yüksekliği görüldü. Sadece tenofovir kullanmış bir hastada osteopeni, 1 hastada ise osteoporoz saptandı. Entekavir kullanan bir hastada kreatinin yüksekliği nedeniyle doz ayarı yapılırken; interferon kullanan bir hastada derin trombositopeni olması nedeniyle tedavi kesildiği, 1 hastada ise allerjik reaksiyon nedeniyle tedavi değişikliği yapıldığı tespit edildi. Telbivudin alan 1 hastada kreatinin fosfokinaz (CK) yüksekliği olması nedeniyle tedavisi kesilmek zorunda kalındığı gözlendi.
Hepatitis B disease is the most common cause of chronic liver disease in the world and can lead to hepatocellular carcinoma, cirrhosis and liver failure. The aim of antiviral therapy is to prevent progression of the disease. And they do it by reducing the viral load and fibrosis. For the treatment the various treatment options that interferon, nucleoside (lamivudine, entecavir, tenofovir) and nucleotide analogues (adefovir, tenofovir) contains are available. These options show different effects on HBV DNA levels, ALT, liver histology, HBeAg and HbsAg and different patient groups' response to treatment in different levels. The aim of this study is to determine similar and different features between the treatment groups by comparing patients' who receive treatment because of hepatitis B at least one year, demographic characteristics, treatment and duration, treatment changes, adverse effect profile, molecular, serological, biochemical and histological characteristics. In this study, 134 patients who get treatment of Hepatitis B at least one year and were admitted to Uludag University School of Medicine the Infectious Diseases and Clinical Microbiology Department between 01.01.2005-31.12.2012 were analyzed retrospectively. Study designed with Uludag University Faculty of Medicine Research Ethics Committee approval. When patients classified by treatment; 22 patients were interferon (16.4%), 48 patients lamivudine (35.8%), 45 patients entecavir (33.5%), 10 patients tenofovir (7.4%), 5 patients telbivudine (3.7%), 1 patient adefovir, 1 patient lamivudine + adefovir,1 patient interferon + entecavir and 1 patient was tenofovir + entecavir treatment group. Patients' interferon treatment's mean duration time was 8.7, lamivudine's 34.6, entecavir's 36.5 and tenofovir's 37.8, telbivudine's 13 months. Our number of patients receiving adefovir therapy is few that's why the mean time of treatment didn't evaluate. There were treatment changes observed at the 12 (54%) of 22 in interferon group, 15 of 48 (31.2%) in lamivudine group, 6 of 45 in entecavir (13%) group,1 of 5 in telbivudine (20%) group and 1 patient who took adefovir and and 1 patient who took lamivudine+adefovir. None of the patients treated with tenofovir had treatment changes. In terms of HBV DNA becoming negative at first year of treatment, there was statistical difference between lamivudin-interferon and lamivudin-entecavir (p<0,026 ve p<0,05); and there is no statistical difference between lamivudin and tenofovir (p=0,35). None of the tenofovir-treated patiens developed resistance with treatment. In lamivudin group, lower resistance levels (15 of 48 patients (%31,2)), in entecavir group, higher resistance levels (5 of 45 patients (%11,2)) was seen compared with other studies. When we detected side effects; osteopenia was seen at a patient whos entecavir switched to tenofovir, phosphorus impairment and creatinine elevation in one patient, osteopenia in one patient and ostroporosis in one patient who use tenofovir. One patient who used entecavir was made dose adjustment because of high level of creatinine and one patient's who used interferon therapy was stopped because of deep thrombocytopenia, and one patients' therapy was changed because of allergic reaction. In1 patient who took telbivudine, creatine phosphokinase (CK) elevation because it was observed that the treatment had to be interrupted.
Hepatitis B disease is the most common cause of chronic liver disease in the world and can lead to hepatocellular carcinoma, cirrhosis and liver failure. The aim of antiviral therapy is to prevent progression of the disease. And they do it by reducing the viral load and fibrosis. For the treatment the various treatment options that interferon, nucleoside (lamivudine, entecavir, tenofovir) and nucleotide analogues (adefovir, tenofovir) contains are available. These options show different effects on HBV DNA levels, ALT, liver histology, HBeAg and HbsAg and different patient groups' response to treatment in different levels. The aim of this study is to determine similar and different features between the treatment groups by comparing patients' who receive treatment because of hepatitis B at least one year, demographic characteristics, treatment and duration, treatment changes, adverse effect profile, molecular, serological, biochemical and histological characteristics. In this study, 134 patients who get treatment of Hepatitis B at least one year and were admitted to Uludag University School of Medicine the Infectious Diseases and Clinical Microbiology Department between 01.01.2005-31.12.2012 were analyzed retrospectively. Study designed with Uludag University Faculty of Medicine Research Ethics Committee approval. When patients classified by treatment; 22 patients were interferon (16.4%), 48 patients lamivudine (35.8%), 45 patients entecavir (33.5%), 10 patients tenofovir (7.4%), 5 patients telbivudine (3.7%), 1 patient adefovir, 1 patient lamivudine + adefovir,1 patient interferon + entecavir and 1 patient was tenofovir + entecavir treatment group. Patients' interferon treatment's mean duration time was 8.7, lamivudine's 34.6, entecavir's 36.5 and tenofovir's 37.8, telbivudine's 13 months. Our number of patients receiving adefovir therapy is few that's why the mean time of treatment didn't evaluate. There were treatment changes observed at the 12 (54%) of 22 in interferon group, 15 of 48 (31.2%) in lamivudine group, 6 of 45 in entecavir (13%) group,1 of 5 in telbivudine (20%) group and 1 patient who took adefovir and and 1 patient who took lamivudine+adefovir. None of the patients treated with tenofovir had treatment changes. In terms of HBV DNA becoming negative at first year of treatment, there was statistical difference between lamivudin-interferon and lamivudin-entecavir (p<0,026 ve p<0,05); and there is no statistical difference between lamivudin and tenofovir (p=0,35). None of the tenofovir-treated patiens developed resistance with treatment. In lamivudin group, lower resistance levels (15 of 48 patients (%31,2)), in entecavir group, higher resistance levels (5 of 45 patients (%11,2)) was seen compared with other studies. When we detected side effects; osteopenia was seen at a patient whos entecavir switched to tenofovir, phosphorus impairment and creatinine elevation in one patient, osteopenia in one patient and ostroporosis in one patient who use tenofovir. One patient who used entecavir was made dose adjustment because of high level of creatinine and one patient's who used interferon therapy was stopped because of deep thrombocytopenia, and one patients' therapy was changed because of allergic reaction. In1 patient who took telbivudine, creatine phosphokinase (CK) elevation because it was observed that the treatment had to be interrupted.
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Keywords
Hepatit B, Direnç, Tedaviye yanıt, Hepatitis B, Resistance, Treatment response
Citation
Yıldırım, D. Ö. (2014). Kronik hepatit B'li hastalarda demografik özelikler, antiviral tedavi ve tedaviye yanıtın karşılaştırılması. Yayınlanmamış uzmanlık tezi. Uludağ Üniversitesi Tıp Fakültesi.