Publication: Karaciğer Sirozu Hastaları'nda Serum Zonulin Düzeyi'nin Spontan Bakteriyel Peritonit Riskini Öngörmedeki Etkisi
Abstract
Giriş ve amaç: Siroz herhangi bir nedenle oluşan kronik karaciğer hastalığının son evresi olup karaciğerde yaygın fibrozis ve rejenerasyon nodülleri ile karakterize bir tablodur. Siroz ilerlediğinde dekompansasyon gelişir ve en sık dekompansasyon şekli assit gelişimidir. Spontan bakteriyel peritonit (SBP) assit sıvısının primer enfeksiyonu olup siroz hastalarında en sık görülen enfeksiyondur. SBP vakalarının yaklaşık 1/3'ü asemptomatik seyretmektedir. Zamanında tedavi edilmeyen SBP'nin hastane içi mortalite oranı %90'larda iken erken teşhis ve tedavi ile bu oran %20'lere kadar geriler. Bu durum SBP gelişimi için yüksek riskli hastaların tespiti ve yakından takibi açısından ilave tanısal değerlendirmelere ihtiyaç olduğunu düşündürmektedir. SBP gelişiminde rol oynayan en önemli mekanizmaların bağırsak geçirgenliğindeki artış ve bakteriyel translokasyon olduğu ileri sürülmektedir. Bağırsak epitel bariyerinin geçirgenliğinin düzenlenmesinde TJ (tight junction) proteinleri görev almaktadır. Zonulin bağırsak geçirgenliğini düzenleyen, hücreler arası TJ proteinlerinden biridir. Çalışmamızda serum Zonulin düzeyinin SBP gelişim riskini öngörme açısından değerinin bulunup bulunmadığının belirlenmesi amaçlanmıştır. Materyal ve metod: Ondokuz Mayıs Üniversitesi Tıp Fakültesi Hastanesi İç Hastalıkları Anabilim Dalı Gastroenteroloji Bilim Dalına Mart 2024-Eylül 2024 tarihleri arasında başvuran 259 gönüllü çalışmaya dahil edildi. Takiplerinde 36 hasta farklı nedenlerden dolayı çalışma dışı bırakıldı. Kalan 223 kişiden 132'si karaciğer siroz tanısına sahipti, 91'i ek hastalığı olmayan grup (kontrol grubu) olarak ayrıldı. Karaciğer sirozlu hastaların 71'i kompanse sirozlu, 46'sı SBP öyküsü olmayan assitli, 15'i SBP öyküsü olan assitli hastalardan oluştu. Serum Zonulin konsantrasyonları Human Zonulin ELISA kit (Sun-Red Bio Company, Cat No. 201-12-5578, Shanghai, China) ile sandwich method enzim immunoassay yöntemi ile çalışıldı. Veriler IBM SPSS V23 ile analiz edildi. Bulgular: SBP gurubu ile kontrol grubunda serum Zonulin değerleri arasında istatistiksel olarak anlamlı farklılık görüldü (p=0;014). Karaciğer siroz hastalığını ayırt etmede Zonulin parametresi için istatistiksel olarak anlamlı bir kesme değer bulunmuştur (p=0,006). Zonulin değeri ≥ 12,84 olanlar hastalığı göstermektedir. Sensitivite (%) değeri %57,58, Spesifite (%) değeri %72,53, PPV değeri %75,25 iken iii NPV değeri %54,10 olarak bulundu. HBV'ye bağlı karaciğer sirozu olan hastalarda diğer etiyolojik nedenlerle kıyasla Zonulin değeri düşük saptandı (p<0,001). Tartışma ve sonuç: SBP, assitli siroz hastalarında sık görülen, ciddi bir komplikasyondur ve tedavi edilmezse hastane içi ölüm oranı %90'ı geçebilir. Tanı konmasında ortaya çıkan zorluklar ve kültür sonuç beklenmesi hastalığın tedavisinde geç kalmamıza neden olmaktadır. Bu nedenle SBP tanısında kolay ulaşılabilir, sensitivite ve spesifitesi yüksek bir biyobelirteçe ihtiyaç vardır. Çalışmamızda serum Zonulin değerinin SBP tanısında klinik açıdan anlamlı olabileceğini düşündüren değerler saptandı. Karaciğer siroz süresi ile Zonulin arasında ilişki saptanmadı. Dalak boyutu ve portal ven çapı ile Zonulin arasında anlamlı ilişki saptandı. Bu ilişki portal basınç ile serum Zonulin düzeyi arasında da ilişki olabileceğini düşündürmüştür. Sonuç olarak SBP tanı ve takibinde Zonulin proteinin rolü hakkında büyük ölçekli çalışmalara ihtiyaç vardır. Anahtar kelimeler: Spontan bakteriyel peritonit, Siroz, Zonulin
Introduction and Aim: Cirrhosis is the end stage of chronic liver disease, caused by any underlying condition, and is characterized by widespread fibrosis and regenerative nodules in the liver. When cirrhosis progresses, decompensation occurs, with the most common form of decompensation being the development of ascites. Spontaneous bacterial peritonitis (SBP) is the primary infection of ascitic fluid and is the most common infection seen in cirrhotic patients. Approximately one-third of SBP cases are asymptomatic. The in-hospital mortality rate of untreated SBP is around 90%, whereas early diagnosis and treatment can reduce this rate to around 20%. This highlights the need for additional diagnostic evaluations to identify high-risk patients for SBP and to monitor them closely. The most significant mechanisms thought to play a role in the development of SBP are increased intestinal permeability and bacterial translocation. Tight junction (TJ) proteins are responsible for regulating the permeability of the intestinal epithelial barrier. Zonulin is one of the TJ proteins that regulates intestinal permeability. Our study aimed to determine whether serum zonulin levels have predictive value for the risk of SBP development. Materials and Methods: A total of 259 volunteers who applied to to Ondokuz Mayıs University Faculty of Medicine Hospital, Department of Internal Medicine, Division of Gastroenterology between March 2024 and September 2024 were included in the study. During follow-up, 36 patients were excluded for various reasons. Of the remaining 223 individuals, 132 had a diagnosis of liver cirrhosis, while 91 were classified as the control group with no additional disease. Among the patients with liver cirrhosis, 71 had compensated cirrhosis, 46 had ascites without a history of SBP, and 15 had ascites with a history of SBP. Serum zonulin concentrations were measured using the Human Zonulin ELISA kit (Sun-Red Bio Company, Cat No. 201-12-5578, Shanghai, China) with the sandwich enzyme immunoassay method. The data were analyzed using IBM SPSS V23. Results: A statistically significant difference in serum zonulin levels was observed between the SBP group and the control group (p=0.014). A statistically significant cutoff value was found for the zonulin parameter in distinguishing liver cirrhosis (p=0.006). A zonulin level of ≥12.84 indicates the presence of the disease. The v sensitivity (%) was found to be 57.58%, specificity (%) was 72.53%, the positive predictive value (PPV) was 75.25%, and the negative predictive value (NPV) was 54.10%. In patients with liver cirrhosis due to HBV, zonulin levels were found to be lower compared to other etiological causes (p<0.001). Discussion and Conclusion: SBP is a common and serious complication in cirrhotic patients with ascites, and if left untreated, the in-hospital mortality rate can exceed 90%. Challenges in diagnosis and waiting for culture results can delay treatment. Therefore, there is a need for an easily accessible biomarker with high sensitivity and specificity for SBP diagnosis. Our study found values that suggest serum zonulin could be clinically significant in diagnosing SBP. No association was found between the duration of liver cirrhosis and zonulin levels. However, a significant relationship was observed between zonulin levels and both spleen size and portal vein diameter, suggesting a potential association between portal pressure and serum zonulin levels. In conclusion, large-scale studies are needed to further explore the role of the zonulin protein in SBP diagnosis and follow-up. Keywords: Spontaneous bacterial peritonitis, Cirrhosis, Zonulin
Introduction and Aim: Cirrhosis is the end stage of chronic liver disease, caused by any underlying condition, and is characterized by widespread fibrosis and regenerative nodules in the liver. When cirrhosis progresses, decompensation occurs, with the most common form of decompensation being the development of ascites. Spontaneous bacterial peritonitis (SBP) is the primary infection of ascitic fluid and is the most common infection seen in cirrhotic patients. Approximately one-third of SBP cases are asymptomatic. The in-hospital mortality rate of untreated SBP is around 90%, whereas early diagnosis and treatment can reduce this rate to around 20%. This highlights the need for additional diagnostic evaluations to identify high-risk patients for SBP and to monitor them closely. The most significant mechanisms thought to play a role in the development of SBP are increased intestinal permeability and bacterial translocation. Tight junction (TJ) proteins are responsible for regulating the permeability of the intestinal epithelial barrier. Zonulin is one of the TJ proteins that regulates intestinal permeability. Our study aimed to determine whether serum zonulin levels have predictive value for the risk of SBP development. Materials and Methods: A total of 259 volunteers who applied to to Ondokuz Mayıs University Faculty of Medicine Hospital, Department of Internal Medicine, Division of Gastroenterology between March 2024 and September 2024 were included in the study. During follow-up, 36 patients were excluded for various reasons. Of the remaining 223 individuals, 132 had a diagnosis of liver cirrhosis, while 91 were classified as the control group with no additional disease. Among the patients with liver cirrhosis, 71 had compensated cirrhosis, 46 had ascites without a history of SBP, and 15 had ascites with a history of SBP. Serum zonulin concentrations were measured using the Human Zonulin ELISA kit (Sun-Red Bio Company, Cat No. 201-12-5578, Shanghai, China) with the sandwich enzyme immunoassay method. The data were analyzed using IBM SPSS V23. Results: A statistically significant difference in serum zonulin levels was observed between the SBP group and the control group (p=0.014). A statistically significant cutoff value was found for the zonulin parameter in distinguishing liver cirrhosis (p=0.006). A zonulin level of ≥12.84 indicates the presence of the disease. The v sensitivity (%) was found to be 57.58%, specificity (%) was 72.53%, the positive predictive value (PPV) was 75.25%, and the negative predictive value (NPV) was 54.10%. In patients with liver cirrhosis due to HBV, zonulin levels were found to be lower compared to other etiological causes (p<0.001). Discussion and Conclusion: SBP is a common and serious complication in cirrhotic patients with ascites, and if left untreated, the in-hospital mortality rate can exceed 90%. Challenges in diagnosis and waiting for culture results can delay treatment. Therefore, there is a need for an easily accessible biomarker with high sensitivity and specificity for SBP diagnosis. Our study found values that suggest serum zonulin could be clinically significant in diagnosing SBP. No association was found between the duration of liver cirrhosis and zonulin levels. However, a significant relationship was observed between zonulin levels and both spleen size and portal vein diameter, suggesting a potential association between portal pressure and serum zonulin levels. In conclusion, large-scale studies are needed to further explore the role of the zonulin protein in SBP diagnosis and follow-up. Keywords: Spontaneous bacterial peritonitis, Cirrhosis, Zonulin
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