HBE antijen negatif kronik Hepatit B'li hastalarda Lamivudin tedavisinin etkinliği

Hepatit B virusu (HBV) ile enfeksiyon global bir saglik sorunu olup, dunya capinda yaklasik 2 milyar kisi bu virusle enfektedir. HBeAg negatif KHB enfeksiyonunun ulkemizde ve diger Akdeniz ulkelerinde prevalansi yuksektir ve dunyada giderek artmaktadir. Bu calismanin amaci, HBeAg negatif KHB'de mortalite ve morbidite oranlarinin ortaya konmasi, uygulanan anti-viral tedavinin (lamivudin) hastalik seyrine ve hasta yasam suresi uzerine etkinligini saptamaktir. Takip sureleri bir yil ve ustunde olan, duzenli takipleri olan ve tek basina veya kombine lamivudin tedavisi alan 180 HBeAg negatif KHB hastasi calismaya alindi. Ortalama takip suresi 50.4 ay. Yuz seksen hastanin lamivudin tedavisine verdigi yanitlara bakildiginda, baslangicta hastalarin %94.4 (170/180)'unde lamivudinle HBVDNA'nin negatiflestigi goruldu. Sadece 10 (%5.6) hastada virolojik yanit alinamadi (primer yanitsiz hastalar). Yanit alinan 170 hastanin 44 (%25.9)'unde virolojik kirilma saptandi. Lamivudin yaniti olan 56 kiside lamivudin tedavisi ortalama 29.8 aylik tedavi sonrasi sonlandirildi. Bunlardan %55.4'unde (31/56) devamli virolojik yanit, %44.6'sinda (25/56) ise nuks saptandi. Nuks eden ve etmeyen grupta lamivudin kullanma sureleri karsilastirildiginda, gruplar arasinda anlamli fark saptanmadi (p=0.6). Tedavi kesildikten sonra yillara gore kumulatif relaps oranlari: 1. yilda %11, 2. yilda %23, 3. yilda % 27 saptandi. Nukleozid analog naive 84 kisinin kumulatif HBVDNA negatiflik oranlarina bakildi. HBVDNA negatiflik oranlari: 6.ayda %87.5, 12.ayda %88.1, 24.ayda %74.1, 36.ayda %71.1, 48.ayda %79.2 bulundu. Lamivudin tedavisi ile ALT normallesme oranlari 6. ayda %69.2, 12. ayda %75.7, 24.ayda %71, 36.ayda %79.5, 48.ayda %84.6 ve 60. ayda %100 saptandi. Takipte, %24 hastada (43/180) YMDD mutasyonu pozitif bulundu. Yillara gore lamivudin tedavisiyle kumulatif direnc oranlarina bakildiginda, 1. yil direnc orani %1, 2. yil %6, 3. yil %9, 4.yil %16 ve 5.yil %20 bulundu. Lamivudin baslandiktan sonra 7 hastada HBsAg serokonversiyonu gelisti (%3.9). Hastalardan 2 tanesinde (%1.1) siroz gelisti, 3 erkek hastada (%1.7) HSK gelisti. Sonuc olarak lamivudin tedavisi, HBeAg negatif KHB hastalarinda replikasyonu inhibe ederek hastaligin klinik progresyonunu onlemektedir.AbstractHepatitis B virus (HBV) infection is a challenging global health problem, affecting an estimated 2 billion persons worldwide. HBeAg negative chronic hepatitis B prevalence is high in our country and Mediterranean region and increasing worldwide. The aims of the study were to investigate the efficacy of anti-viral (lamivudine) therapy in HBeAg negative chronic hepatitis B (CHB) patients and to determine mortality and morbidity rates in HBeAg negative chronic hepatitis B. One hundred and eighty person treated with single or combined lamivudine therapy and has at least one year follow-up time, included to the research. Mean follow-up time was 50.4 months. At the beginning of the therapy, 94.4% (170/180) of individuals? HBVDNA became undetectable only 10 (5.6%) patients did not achieve a virological response (primary non-response). Virological breakthrough associated with HBVDNA detectability was observed in 44 of 170 CHB patients (25.9%). Lamivudine therapy was withdrawn in 56 CHB patients who are under virological response with lamivudine therapy: 55.4% (31/56) of the patients achieved a sustained virological response, but 44.6% (25/56) of the patients had virological relapse. Lamivudine treatment durations were statistically similar between these 2 groups (sustained virological response vs virological relaps) (p=0.6). The cumulative relapse rate increased steadily over time and was as follows: 11%, 23% and 27% at months 12,24 and 36 respectively. Te cumulative probability of becoming HBVDNA undetectable was determined and was as follows: 87.5%, 88.1%, 74.1%, 71.1% and 79.2% at months 6,12,24,36 and 48 respectively. The rate of serum ALT levels under 37 IU/mL at baseline was 6.2%. After treatment ALT normalization rates were 69.2%, 75.7%, 71%, 79.5% and 84.6% at months 6,12,24,36 and 48 respectively which indicates lamivudine is effective on lowering serum ALT levels. YMDD mutation motifs were found in 24% (43/180) of patients. The cumulative anti-viral resistance rates were 1%, 6%, 9%, 16% and 20% at months 12,24,36,48 ad 60 respectively. During the follow-up, HBsAg seroconversion was achieved at 7 (3.9%) patients, 2 (1.1%) patients developed cirrhosis and 3 (1.7%) patients developed hepatocellular cancer. Based on the results of the study lamivudine therapy is effective in suppressing viral load and prevents clinical deterioration in HBeAg negative CHB patients.