HBeAg negatif kronik hepatit B infeksiyonlu hastalarda PCR yöntemiyle düşük hepatit B viremi düzeylerinin saptanması
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2017
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info:eu-repo/semantics/embargoedAccess
Özet
AMAÇ: Kronik HBV infeksiyonunda viral yükün belirlenmesi hastalığın doğal seyrinin daha iyi anlaşılması, tedavi kararının verilmesi, tedavi yanıtının değerlendirilmesi ve ilaç direnci gelişiminin gösterilmesinde oldukça önemlidir. Bu çalışmada standart sıvı hibridizasyon yöntemleriyle serum HBV-DNA düzeyi tespit edilemeyen ancak aminotransferazlan devamlı yüksek seyreden HBsAg+/anti-HBe+ hasta grubu incelendi. Bu hastalarda diğer tüm etyolojik nedenler ekarte edildikten sonra aminotransferaz yüksekliğine neden olabilecek HBV'ye ait düşük viremi düzeyini saptamayı hedefledik. Ayrıca bu grup hastalan inaktif HBsAg taşıyıcılarından ayırt edebilecek bir viral cut-off değerinin varlığını saptamayı amaçladık. HASTA VE YÖNTEM: Çalışmaya HBsAg+/anti-HBe+, HBV-DNA'sı ise standart hibridizasyon yöntemiyle (Digene Hybride) saptanamayan 183, ALT' si normal ve yüksek olan hastalar dahil edildi. Hastalar biyokimyasal, hematolojik, serolojik, virolojik ve demografik yönden incelendi. Tüm hastalarda düşük viral DNA düzeyini saptamayı sağlayan ve kantitatif PCR yöntemi olan Cobas Amplicor HBV monitor testi kullanıldı. BULGULAR: Çalışmaya alman hastaların 25 'i dışlandı; 19'u HDV infeksiyonu, 4'ü NASH, 2'si siroz nedeniyle dışlandı. Kalan 158 hastanın 81'i ALT yüksekliği devam eden düşük viremi düzeyli kronik hepatit B (grup 1), 77' si ise inaktif HBsAg taşıyıcısından (grup 2) oluşmaktaydı. Yaş ortalaması 1. grupta 33. 78± 10.03, ikinci grupta ise 35.08±8.57 (p=0.384). Erkek/kadın oram grup l'de 69/12 (%85), grup 2'de 43/34 idi (%56) (p<0.001). ALT düzeyleri 1. ve 2. grupta sırayla 68.01±33.38 U/L ve 22.55Ü0.79 U/L idi (pO.001). AST düzeyleri ise yine sırayala 45.68±27.9 U/L ve 21.15±5.49 U/L idi (pO.001). Total bilirubin (p=0.158), albumin düzeyi (p=0.271) ve protrombin zamanı (p=0.586) bakımından gruplar arasında fark saptanmadı. HBV-DNA düzeyi 1. grupta 91029±165716 kopya/ml, 2. grupta ise 26625±70049 kopya/ml bulundu (p=O.002). HBsAg düzeyleri bakırnından ise gruplar arasında anlamlı fark saptanmadı (p=0.498). SONUÇ: Bu çalışmada HBsAg+/anti-HBe pozitif ve aminotransferazlan yüksek seyreden ancak standart hibridizasyon yöntemiyle HBV-DNA'sı saptanamayan hastalarda viral replikasyonun düşük düzeylerde devam ettiği ve düşük düzeyli viremiye ifi rağmen aktif nekroinflamatuar bulguların olabileceği sonucuna varılmıştır. Bu hastalar bilinen klasik kronik aktif hepatit B'li hastalar gibi değelendirilmeli ve tedavi edilmelidirler. Ayrıca düşük viral yükün gösterilmesinde kantitatif bir PCR yöntemi olan Cobas Amplicor HBV monitor testi duyarlı bir testtir. Ancak bu hastaların tanısında ve takiplerinde serum ALT düzeyleri ile karaciğer biyopsisinin önemli bir role sahip olduğu unutulmamalıdır. înaktif HBsAg taşıyıcılarının ise sürekli normal transaminaz değerlerine ve daha düşük serum HB V-DNA düzeylerine sahip olduğu gösterilmiştir.
Detection of viremia levels in chronic hepatitis B virus infection is crucial in recognizing the state of the disease, deciding to start the therapy, determining te results of the treatment and indicating the drug resistance. In this study, patients with HBsAg+/anti-HBe+ and high aniinotransfefase, whose serum HBV-DNA levels were not detected with standard liquit hybridization assay were examined. We aimed to determine the level of low viremia of HBV infection that can lead to high aminotransferase levels after excluding other aethiological factors. Also we aimed to determine a viral cut-off value in discriminating these patients from inactive HBsAg carriers. PATIENT AND METHOD: 183 HBsAg+/anti-HBe+ patients whose HBV-DNA can not detected with standart hybridization assay (Digene Hybride), with high and normal ALT levels, were included. All biochemical,serological,virologic and demographic variables were examined.At all patients, quantitative PCR assay, Cobas Amplicor HBV monitor test, were used for detecting low viral DNA levels. RESULTS: 25 patients were exclude; 19 for HDV infection, 4 for NASH, 2 for chirrosis. Of remainder 158 patients, 81 patients were chronic hepatitis B with low viremia level with high ALT (group 1), 77 patients were inactive HBsAg carrier (group 2). Mean age was 33.78±10.03 in groupl and 35.08±8.57 in group 2 (p=0.384). Male/female ratio is 69/12 (%85) in group 1, 43/34 (%56) in group 2 (p<0.001). ALT levels are 68.0U33.38 U/L and 22.55±10.79 U/L (p<0.001) in group 1 and 2, respectively. AST levels are 45.68±27.9 U/L and 21.15±5.49 U/L (p<0.001) in group 1 and 2 respectively. No significance difference for total billiurubine (p=0.158), albumine level (p=0.271) and prothrombine time (p=0.586) were detected. HBV-DNA level was 91029±165716 kopya/ml in group 1 and 26625±70049 kopya/ml in group 2 (p=0.002). There was no significant between HBsAg levels of groups (p=0.498). 38 CONCLUSION: İh this study in HBsAg+/anti-HBe+ patients whose aminotransferases were high and HBV-DNA can not detected with standard hybridization assay, viral replication continiue at low levels and in front of low viremia level there can be necro-inflamatuar signs.These patients should be determined and treated as classic chronic active hepatitis B. Cobas Amplicor HBV monitoring test, a quantitative PCR method, is a sensitive detecting low levels of viremia. Serum ALT levels and liver biopsy plays an important role in the diagnosis and follow-up of these patients. Also it was indicated that inactive HBsAg carriers have normal levels of transaminase and low levels HBV- DNA.
Detection of viremia levels in chronic hepatitis B virus infection is crucial in recognizing the state of the disease, deciding to start the therapy, determining te results of the treatment and indicating the drug resistance. In this study, patients with HBsAg+/anti-HBe+ and high aniinotransfefase, whose serum HBV-DNA levels were not detected with standard liquit hybridization assay were examined. We aimed to determine the level of low viremia of HBV infection that can lead to high aminotransferase levels after excluding other aethiological factors. Also we aimed to determine a viral cut-off value in discriminating these patients from inactive HBsAg carriers. PATIENT AND METHOD: 183 HBsAg+/anti-HBe+ patients whose HBV-DNA can not detected with standart hybridization assay (Digene Hybride), with high and normal ALT levels, were included. All biochemical,serological,virologic and demographic variables were examined.At all patients, quantitative PCR assay, Cobas Amplicor HBV monitor test, were used for detecting low viral DNA levels. RESULTS: 25 patients were exclude; 19 for HDV infection, 4 for NASH, 2 for chirrosis. Of remainder 158 patients, 81 patients were chronic hepatitis B with low viremia level with high ALT (group 1), 77 patients were inactive HBsAg carrier (group 2). Mean age was 33.78±10.03 in groupl and 35.08±8.57 in group 2 (p=0.384). Male/female ratio is 69/12 (%85) in group 1, 43/34 (%56) in group 2 (p<0.001). ALT levels are 68.0U33.38 U/L and 22.55±10.79 U/L (p<0.001) in group 1 and 2, respectively. AST levels are 45.68±27.9 U/L and 21.15±5.49 U/L (p<0.001) in group 1 and 2 respectively. No significance difference for total billiurubine (p=0.158), albumine level (p=0.271) and prothrombine time (p=0.586) were detected. HBV-DNA level was 91029±165716 kopya/ml in group 1 and 26625±70049 kopya/ml in group 2 (p=0.002). There was no significant between HBsAg levels of groups (p=0.498). 38 CONCLUSION: İh this study in HBsAg+/anti-HBe+ patients whose aminotransferases were high and HBV-DNA can not detected with standard hybridization assay, viral replication continiue at low levels and in front of low viremia level there can be necro-inflamatuar signs.These patients should be determined and treated as classic chronic active hepatitis B. Cobas Amplicor HBV monitoring test, a quantitative PCR method, is a sensitive detecting low levels of viremia. Serum ALT levels and liver biopsy plays an important role in the diagnosis and follow-up of these patients. Also it was indicated that inactive HBsAg carriers have normal levels of transaminase and low levels HBV- DNA.
Açıklama
Anahtar Kelimeler
Kronik HBV infeksiyonu, Tedavi, Hepatit B virüsü, Hepatitis B virus