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Zonulin is not Useful for the Diagnosis of Intestinal Permeability in Cirrhotic

Year 2023, Volume: 76 Issue: 4, 328 - 332, 05.04.2024

Abstract

Objectives: Increased intestinal permeability is an important cause of serious complications in cirrhotic. In addition, intestinal permeability can promote impaired liver functions. Zonulin, well-known intestinal permeability marker, has never studied sufficiently before in cirrhotic as a potential marker of increased intestinal permeability.

Materials and Methods: This is a cross-sectional study. Forty-one cirrhotic patients (11 patients in compensated phase and 30 patients in decompensated phase) were enrolled into the study. Meanwhile forty-one healthy controls were also enrolled. Zonulin was assessed by enzymelinked immunosorbent assay technique.

Results: Zonulin levels was not significantly different between patients with cirrhotic and healthy individuals; however lower levels was observed in cirrhotic (p=0.068). In patients with cirrhotic, zonulin level was significantly different between child-pugh A and child-pugh B (p=0.05). Also zonulin was significantly lower in child-pugh C compared to child-pugh-A and child-pugh-B (p=0.011 and p=0.026, respectively). In all patients with cirrhotic, MELD score was positively correlated with zonulin levels (p=0.001, R=0.358).

Conclusion: This study reveals that serum zonulin levels were decreased, especially in decompensated phase in cirrhotic compared to healthy individuals. It is possible to speculate that zonulin is not a causal factor for intestinal permeability in cirrhotic, instead of this, its synthesis effects negatively in cirrhotic situation.

Key Words: Cirrhotic, Intestinal Permeability, Zonulin

Project Number

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References

  • 1. Iida H, Osaki R, Fujimoto T, et al. Interval between hepatocellular carcinoma treatment and interferon-free direct-acting antiviral agents against hepatitis C is necessary to suppress tumor recurrence. Mol Clin Oncol. 2019;11:99-105.
  • 2. Lv Y, Yang Z, Liu L, et al. Early TIPS with covered stents versus standard treatment for acute variceal bleeding in patients with advanced cirrhosis: a randomised controlled trial. Lancet Gastroenterol Hepatol. 2019;4:587-598.
  • 3. Thalheimer U, De Iorio F, Capra F, et al. Altered intestinal function precedes the appearance of bacterial DNA in serum and ascites in patients with cirrhosis: a pilot study. Eur J Gastroenterol Hepatol. 2010;22:1228-1234.
  • 4. Runyon BA; AASLD Practice Guidelines Committee. Management of adult patients with ascites due to cirrhosis: an update. Hepatology. 2009;49:2087- 2107.
  • 5. Ohlsson B, Orho-Melander M, Nilsson PM. Higher Levels of Serum Zonulin May Rather Be Associated with Increased Risk of Obesity and Hyperlipidemia Than with Gastrointestinal Symptoms or Disease Manifestations. Int J Mol Sci. 2017;18:582.
  • 6. Tripathi A, Lammers KM, Goldblum S, et al. Identification of human zonulin, a physiological modulator of tight junctions, as prehaptoglobin-2. Proc Natl Acad Sci U S A. 2009;106:16799-16804.
  • 7. Watts T, Berti I, Sapone A, et al. Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabeticprone rats. Proc Natl Acad Sci U S A. 2005;102:2916-2921.
  • 8. Duerksen DR, Wilhelm-Boyles C, Veitch R, et al. A comparison of antibody testing, permeability testing, and zonulin levels with small-bowel biopsy in celiac disease patients on a gluten-free diet. Dig Dis Sci. 2010;55:1026-1031.
  • 9. Sapone A, de Magistris L, Pietzak M, et al. Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes. 2006;55:1443-1449.
  • 10. Akao T, Morita A, Onji M, et al. Low Serum Levels of Zonulin in Patients with HCV-Infected Chronic Liver Diseases. Euroasian J Hepatogastroenterol. 2018;8:112-115.
  • 11. Calgin MK, Cetinkol Y. Decreased levels of serum zonulin and copeptin in chronic Hepatitis-B patients. Pak J Med Sci. 2019;35:847-851.
  • 12. Such J, Guardiola JV, de Juan J, et al. Ultrastructural characteristics of dist duodenum mucosa in patients with cirrhosis. Eur J Gastroenterol Hepatol. 2002;14:371-376.
  • 13. Ramachandran A, Prabhu R, Thomas S, et al. Intestinal mucosal alterations in experimental cirrhosis in the rat: role of oxygen free radicals. Hepatology. 2002;35:622-629.
  • 14. Wen JB, Zhu FQ, Chen WG, et al. Oxymatrine improves intestinal epithelial barrier function involving NF-κB-mediated signaling pathway in CCl4-induced cirrhotic rats. PLoS One. 2014;9:e106082.
  • 15. Sturgeon C, Fasano A. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases. Tissue Barriers. 2016;4:e1251384.
  • 16. Fasano A, Not T, Wang W, et al. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet. 2000;355:1518-1519.
  • 17. Assimakopoulos SF, Tsamandas AC, Tsiaoussis GI, et al. Altered intestinal tight junctions’ expression in patients with liver cirrhosis: a pathogenetic mechanism of intestinal hyperpermeability. Eur J Clin Invest. 2012;42:439-446.
  • 18. Pijls KE, Koek GH, Elamin EE, et al. Large intestine permeability is increased in patients with compensated liver cirrhosis. Am J Physiol Gastrointest Liver Physiol. 2014;306:G147-G153.

Zonulin Sirozlu Hastalarda İntestinal Geçirgenlik Tanısında Kullanışlı Değildir

Year 2023, Volume: 76 Issue: 4, 328 - 332, 05.04.2024

Abstract

Amaç: Sirozlu hastalarda artmış intestinal geçirgenlik ciddi komplikasyonların önemli bir nedenidir. Ek olarak artmış intestinal geçirgenlik karaciğer fonksiyonlarında kötüleşmeye de yol açar. Zonulin, intestinal geçirgenlik için iyi tanımlanmış bir belirteç olsa da, sirozlu hastalarda artmış intestinal geçirgenlik varlığının tanısında yeterince çalışılmamıştır.

Gereç ve Yöntem: Bu çalışma kesitsel bir çalışmadır. Kırk bir siroz tanılı hasta (11 tanesi kompanse, 30 tanesi ise dekompanse fazda olan) çalışmaya dahil edilmiştir. Eş zamanlı 41 sağlıklı kontrol grubu da çalışmaya alınmıştır. Zonulin enzyme-linked immunosorbent assay ile çalışılmıştır.

Bulgular: Zonulin seviyeleri sirozlu hastalar ve sağlıklı bireyler arasında önemli ölçüde farklı değildi; ancak sirozda daha düşük seviyeler gözlendi (p=0,068). Sirozlu hastalarda zonulin düzeyi, child-pugh A ve child-pugh B arasında anlamlı olarak farklıydı (p=0,05). Ayrıca zonulin, child-pugh C’de child-pugh-A ve child-pugh-B’ye göre anlamlı olarak daha düşüktü (sırasıyla p=0,011 ve p=0,026). Tüm sirozlu hastalarda MELD skoru zonulin seviyeleri ile pozitif korelasyon gösterdi (p=0,001, R=0,358).

Sonuç: Bu çalışma, sağlıklı bireylere göre sirozda özellikle dekompanse fazda serum zonulin düzeylerinin azaldığını ortaya koymaktadır. Sirozda zonülinin İP için nedensel bir faktör olmadığı, bunun yerine sentezinin sirotik durumda olumsuz etkilendiği söylenebilir.

Anahtar Kelimeler: Siroz, İntestinal Geçirgenlik, Zonulin

Ethical Statement

Ethics Committee Approval: The study protocol was approved by the Ethics Committee of Keçiören Training and Research Hospital (approval no: 2012-KAEK-15/1825, date: 13.02.2019). Informed Consent: All individuals gave written informed consent. Peer-review: Externally peer-reviewed

Supporting Institution

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Project Number

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Thanks

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References

  • 1. Iida H, Osaki R, Fujimoto T, et al. Interval between hepatocellular carcinoma treatment and interferon-free direct-acting antiviral agents against hepatitis C is necessary to suppress tumor recurrence. Mol Clin Oncol. 2019;11:99-105.
  • 2. Lv Y, Yang Z, Liu L, et al. Early TIPS with covered stents versus standard treatment for acute variceal bleeding in patients with advanced cirrhosis: a randomised controlled trial. Lancet Gastroenterol Hepatol. 2019;4:587-598.
  • 3. Thalheimer U, De Iorio F, Capra F, et al. Altered intestinal function precedes the appearance of bacterial DNA in serum and ascites in patients with cirrhosis: a pilot study. Eur J Gastroenterol Hepatol. 2010;22:1228-1234.
  • 4. Runyon BA; AASLD Practice Guidelines Committee. Management of adult patients with ascites due to cirrhosis: an update. Hepatology. 2009;49:2087- 2107.
  • 5. Ohlsson B, Orho-Melander M, Nilsson PM. Higher Levels of Serum Zonulin May Rather Be Associated with Increased Risk of Obesity and Hyperlipidemia Than with Gastrointestinal Symptoms or Disease Manifestations. Int J Mol Sci. 2017;18:582.
  • 6. Tripathi A, Lammers KM, Goldblum S, et al. Identification of human zonulin, a physiological modulator of tight junctions, as prehaptoglobin-2. Proc Natl Acad Sci U S A. 2009;106:16799-16804.
  • 7. Watts T, Berti I, Sapone A, et al. Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabeticprone rats. Proc Natl Acad Sci U S A. 2005;102:2916-2921.
  • 8. Duerksen DR, Wilhelm-Boyles C, Veitch R, et al. A comparison of antibody testing, permeability testing, and zonulin levels with small-bowel biopsy in celiac disease patients on a gluten-free diet. Dig Dis Sci. 2010;55:1026-1031.
  • 9. Sapone A, de Magistris L, Pietzak M, et al. Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes. 2006;55:1443-1449.
  • 10. Akao T, Morita A, Onji M, et al. Low Serum Levels of Zonulin in Patients with HCV-Infected Chronic Liver Diseases. Euroasian J Hepatogastroenterol. 2018;8:112-115.
  • 11. Calgin MK, Cetinkol Y. Decreased levels of serum zonulin and copeptin in chronic Hepatitis-B patients. Pak J Med Sci. 2019;35:847-851.
  • 12. Such J, Guardiola JV, de Juan J, et al. Ultrastructural characteristics of dist duodenum mucosa in patients with cirrhosis. Eur J Gastroenterol Hepatol. 2002;14:371-376.
  • 13. Ramachandran A, Prabhu R, Thomas S, et al. Intestinal mucosal alterations in experimental cirrhosis in the rat: role of oxygen free radicals. Hepatology. 2002;35:622-629.
  • 14. Wen JB, Zhu FQ, Chen WG, et al. Oxymatrine improves intestinal epithelial barrier function involving NF-κB-mediated signaling pathway in CCl4-induced cirrhotic rats. PLoS One. 2014;9:e106082.
  • 15. Sturgeon C, Fasano A. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases. Tissue Barriers. 2016;4:e1251384.
  • 16. Fasano A, Not T, Wang W, et al. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet. 2000;355:1518-1519.
  • 17. Assimakopoulos SF, Tsamandas AC, Tsiaoussis GI, et al. Altered intestinal tight junctions’ expression in patients with liver cirrhosis: a pathogenetic mechanism of intestinal hyperpermeability. Eur J Clin Invest. 2012;42:439-446.
  • 18. Pijls KE, Koek GH, Elamin EE, et al. Large intestine permeability is increased in patients with compensated liver cirrhosis. Am J Physiol Gastrointest Liver Physiol. 2014;306:G147-G153.
There are 18 citations in total.

Details

Primary Language English
Subjects Gastroenterology Surgery
Journal Section Articles
Authors

Muhammet Yener Akpınar 0000-0003-0903-4664

Project Number -
Publication Date April 5, 2024
Published in Issue Year 2023 Volume: 76 Issue: 4

Cite

APA Akpınar, M. Y. (2024). Zonulin is not Useful for the Diagnosis of Intestinal Permeability in Cirrhotic. Ankara Üniversitesi Tıp Fakültesi Mecmuası, 76(4), 328-332. https://doi.org/10.4274/atfm.galenos.2023.50479
AMA Akpınar MY. Zonulin is not Useful for the Diagnosis of Intestinal Permeability in Cirrhotic. Ankara Üniversitesi Tıp Fakültesi Mecmuası. April 2024;76(4):328-332. doi:10.4274/atfm.galenos.2023.50479
Chicago Akpınar, Muhammet Yener. “Zonulin Is Not Useful for the Diagnosis of Intestinal Permeability in Cirrhotic”. Ankara Üniversitesi Tıp Fakültesi Mecmuası 76, no. 4 (April 2024): 328-32. https://doi.org/10.4274/atfm.galenos.2023.50479.
EndNote Akpınar MY (April 1, 2024) Zonulin is not Useful for the Diagnosis of Intestinal Permeability in Cirrhotic. Ankara Üniversitesi Tıp Fakültesi Mecmuası 76 4 328–332.
IEEE M. Y. Akpınar, “Zonulin is not Useful for the Diagnosis of Intestinal Permeability in Cirrhotic”, Ankara Üniversitesi Tıp Fakültesi Mecmuası, vol. 76, no. 4, pp. 328–332, 2024, doi: 10.4274/atfm.galenos.2023.50479.
ISNAD Akpınar, Muhammet Yener. “Zonulin Is Not Useful for the Diagnosis of Intestinal Permeability in Cirrhotic”. Ankara Üniversitesi Tıp Fakültesi Mecmuası 76/4 (April2024), 328-332. https://doi.org/10.4274/atfm.galenos.2023.50479.
JAMA Akpınar MY. Zonulin is not Useful for the Diagnosis of Intestinal Permeability in Cirrhotic. Ankara Üniversitesi Tıp Fakültesi Mecmuası. 2024;76:328–332.
MLA Akpınar, Muhammet Yener. “Zonulin Is Not Useful for the Diagnosis of Intestinal Permeability in Cirrhotic”. Ankara Üniversitesi Tıp Fakültesi Mecmuası, vol. 76, no. 4, 2024, pp. 328-32, doi:10.4274/atfm.galenos.2023.50479.
Vancouver Akpınar MY. Zonulin is not Useful for the Diagnosis of Intestinal Permeability in Cirrhotic. Ankara Üniversitesi Tıp Fakültesi Mecmuası. 2024;76(4):328-32.