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The Utility of M30 and M65 Antigen Concentration Levels for Predicting Degree of Hepatic Injury in Patients with Chronic Hepatitis B Infection

Year 2018, Volume: 17 Issue: 2, 45 - 49, 24.09.2018
https://doi.org/10.17941/agd.456947

Abstract

Background and aims: We aimed to determine the utility of M30 and M65 antigen
concentration levels for predicting hepatic injury in chronic hepatitis B disease.

Materials and Methods: This study
compared concentration levels of M30 and M65 antigens between patients with hepatitis
B e-antigen negative chronic hepatitis B and healthy subjects. Furthermore, the
correlations between either M30 or M65 antigen levels and aspartate
aminotransferase, alanine aminotransferase, HBV-DNA, histological activity
index and fibrosis were
evaluated in the patient group.

Results: A total of
81 subjects were included in the study; 50 patients with HBeAg negative chronic
hepatitis B and 31 healthy subjects. The concentration of the M30 antigen was
significantly higher in the chronic hepatitis B patient group than in the
healthy subject group (p <0.05). However, there was no difference in M65
antigen concentration values between the two groups (p >0.05). Correlation
analysis performed in the patient group revealed a significant correlation
between M30 antigen concentration levels and aspartate aminotransferase levels
(r: 0.207, p <0.05), and between M65 antigen concentration levels and
HBV-DNA levels (r: 0.204, p <0.05). There was no significant correlation
observed between M30 or M65 antigen concentration levels and both the histological
activity index and fibrosis.







Discussion: The presence of high M30 antigen levels in HBeAg negative chronic
hepatitis B patients may suggest that M30 antigen concentration might be
beneficial in disease monitoring and evaluation of treatment efficacy. This
observation must be tested further in more comprehensive studies. However, the
absence of a significant correlation between the concentration levels of either
antigen or both the histological activity index and fibrosis suggests that pathological
examination is unique in detecting hepatic injury.

References

  • References 1. Ganem D, Prince AM. Hepatitis B virus infection--natural history and clinical consequences. N Engl J Med 2004;350:1118-29.
  • 2. Hoofnagle JH, Doo E, Liang TJ, et al. Management of hepatitis B: summary of a clinical research workshop. Hepatology 2007;45:1056-75.
  • 3. Liaw YF. Prevention and surveillance of hepatitis B virus-related hepatocellular carcinoma. Semin Liver Dis 2005;25:40-7.
  • 4. Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology 2007;45:507-39.
  • 5. Fischer R, Baumert T, Blum HE. Hepatitis C virus infection and apoptosis. World J Gastroenterol 2007;13:4865-72.
  • 6. Lapierre P, Beland K, Alvarez F. Pathogenesis of autoimmune hepatitis: from break of tolerance to immune-mediated hepatocyte apoptosis. Transl Res 2007;149:107-13.
  • 7. Day CP. Apoptosis in alcoholic hepatitis: a novel therapeutic target? J Hepatol 2001;34:330-3.
  • 8. Assuncao Guimaraes C and Linden R. Programmed cell deaths. Apoptosis and alternative deathstyles. Eur J Biochem 2004;271:1638-50.
  • 9. Wyllie AH, Morris RG, Smith AL, Dunlop D. Chromatin cleavage in apoptosis: association with condensed chromatin morphology and dependence on macromolecular synthesis. J Pathol 1984;142:67-77.
  • 10. Öktem S, Özhan MH, Özol D. The importance of apoptosis. Toraks Dergisi 2001;2:91-5.
  • 11. CB T. Apoptosis. Lippincott- Raven Publishers, 1999.
  • 12. Ulukaya E, Yilmaztepe A, Akgoz S, et al. The levels of caspase-cleaved cytokeratin 18 are elevated in serum from patients with lung cancer and helpful to predict the survival. Lung Cancer 2007;56:399-404.
  • 13. Smith F. The molecular genetics of keratin disorders. Am J Clin Dermatol 2003;4:347-64.
  • 14. Quinlan RA, Schiller DL, Hatzfeld M, et al. Patterns of expression and organization of cytokeratin intermediate filaments. Ann N Y Acad Sci 1985;455:282-306.
  • 15. Kramer G, Erdal H, Mertens HJ, et al. Differentiation between cell death modes using measurements of different soluble forms of extracellular cytokeratin 18. Cancer Res 2004;64:1751-6.
  • 16. Kronenberger B, Wagner M, Herrmann E, et al. Apoptotic cytokeratin 18 neoepitopes in serum of patients with chronic hepatitis C. J Viral Hepat 2005;12:307-14.
  • 17. Bantel H, Lugering A, Heidemann J, et al. Detection of apoptotic caspase activation in sera from patients with chronic HCV infection is associated with fibrotic liver injury. Hepatology 2004;40:1078-87.
  • 18. European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2017;67:370-98.
  • 19. Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology 2009;50:661-2.
  • 20. McMahon BJ. The natural history of chronic hepatitis B virus infection. Hepatology 2009;49(5 Suppl):S45-55.
  • 21. Kronenberger B, Zeuzem S, Sarrazin C, et al. Dynamics of apoptotic activity during antiviral treatment of patients with chronic hepatitis C. Antivir Ther 2007;12:779-87.
  • 22. Hotchkiss RS, Strasser A, McDunn JE, Swanson PE. Cell death. N Engl J Med 2009;361:1570-83.
  • 23. Farnik H, Lange CM, Hofmann WP, et al Nucleos(t)ide analogue treatment reduces apoptotic activity in patients with chronic hepatitis B. J Clin Virol 2011;52:204-9.
  • 24. Papatheodoridis GV, Hadziyannis E, Tsochatzis E, et al. Serum apoptotic caspase activity as a marker of severity in HBeAg-negative chronic hepatitis B virus infection. Gut 2008;57:500-6.
  • 25. Yilmaz Y, Dolar E, Ulukaya E, et al. Elevated serum levels of caspase-cleaved cytokeratin 18 (CK18-Asp396) in patients with nonalcoholic steatohepatitis and chronic hepatitis C. Med Sci Monit 2009;15:CR189-93.
  • 26. Tabuchi M, Tomioka K, Kawakami T, et al. Serum cytokeratin 18 M30 antigen level and its correlation with nutritional parameters in middle-aged Japanese males with nonalcoholic fatty liver disease (NAFLD). J Nutr Sci Vitaminol (Tokyo) 2010;56:271-8.

Kronik Hepatit B Enfeksiyonunda Hepatik Hasar Düzeyinin Öngörülmesinde M30 ve M65 Antijen Düzeylerinin Etkinliği

Year 2018, Volume: 17 Issue: 2, 45 - 49, 24.09.2018
https://doi.org/10.17941/agd.456947

Abstract

Giriş: Tüm hepatit türlerinde inflamatuvar olay nekroz
ve apopitozu içeren farklı mekanizmalar ile hepatosit ölümüne sebep olur.
M30-antijen apoptozis esnasında kaspazlar tarafından parçalanmış CK18 düzeylerini
ölçmede, M65-antijen ise nekroza giden hücrelerden salgılanan total CK18
düzeylerini ölçmede kullanılır. Bu iki marker’ın kronik hepatit B
enfeksiyonunda kullanımı ile ilgili sınırlı sayıda çalışma mevcuttur. Biz bu
çalışmada M30 ve M65 antijen düzeylerinin, kronik hepatit B hastalığında
karaciğer hasarını göstermede kullanılabilir olup olmadığını göstermeyi
amaçladık. Gereç ve
Yöntem:
Bu çalışmada, Katip
Çelebi Üniversitesi, İzmir Atatürk Eğitim ve Araştırma Hastanesi,
Gastroenteroloji polikliniğine başvuran kronik hepatit B enfeksiyonlu hastalar
ve sağlıklı kontrol grubunda, M30 ve M65 antijen düzeyleri ölçüldü ve çalışma
sonunda elde edilen veriler karşılaştırıldı. Kronik aktif hepatit B
enfeksiyonlu hastalarda ve sağlıklı kontrol grubunda M30 ve M65 antijen
düzeyleri karşılaştırıldı. Ayrıca hasta grupta M30-M65 düzeyleri ile aspartat
aminotransferaz, alanin aminotransferaz, hepatit B virus DNA, histoloji
aktivite indeksi ve fibrozis düzeyleri arasındaki ilişki değerlendirildi. Bulgular: Çalışmaya 50 kronik aktif hepatit B hastası ve 31 sağlıklı
kontrol olmak üzere toplam 81 hasta alındı. Hepatit B hasta grubunda
M30-antijen düzeyi kontrol grubuna göre anlamlı düzeyde yüksek bulundu
(p<0.05), ancak iki grup arasında M65-antijen düzeyleri açısından anlamlı
fark saptanmadı (p>0.05). Hasta grupta yapılan korelasyon analizinde
M30-antijen ile aspartat aminotransferaz arasında (r:0.207, p<0.05),
M65-antijen ile hepatit B virus DNA arasında anlamlı ilişki saptandı (r:0.204,
p<0.05). M30-M65-antijen ile histoloji aktivite indeksi ve fibrozis arasında
anlamlı ilişki saptanmadı. Sonuç: Apopitoz
belirteci olan M30 düzeylerinin kronik aktif hepatit B hastalarında yüksek
saptanması bize M30 düzeylerinin daha kapsamlı çalışmalar ile hastalık
takibinde, hatta hastalara verilen tedavinin etkinliğinin değerlendirilmesinde
faydalı bilgiler sağlayabileceğini düşündürdü. Ancak M30-M65 düzeyleri ile histoloji
aktivite indeksi ve fibrozis arasında anlamlı ilişki olmamasının, patolojinin
karaciğer hasarı tespitinde rakipsiz olduğunu bir kez daha ispatladığını
düşünüyoruz. 

References

  • References 1. Ganem D, Prince AM. Hepatitis B virus infection--natural history and clinical consequences. N Engl J Med 2004;350:1118-29.
  • 2. Hoofnagle JH, Doo E, Liang TJ, et al. Management of hepatitis B: summary of a clinical research workshop. Hepatology 2007;45:1056-75.
  • 3. Liaw YF. Prevention and surveillance of hepatitis B virus-related hepatocellular carcinoma. Semin Liver Dis 2005;25:40-7.
  • 4. Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology 2007;45:507-39.
  • 5. Fischer R, Baumert T, Blum HE. Hepatitis C virus infection and apoptosis. World J Gastroenterol 2007;13:4865-72.
  • 6. Lapierre P, Beland K, Alvarez F. Pathogenesis of autoimmune hepatitis: from break of tolerance to immune-mediated hepatocyte apoptosis. Transl Res 2007;149:107-13.
  • 7. Day CP. Apoptosis in alcoholic hepatitis: a novel therapeutic target? J Hepatol 2001;34:330-3.
  • 8. Assuncao Guimaraes C and Linden R. Programmed cell deaths. Apoptosis and alternative deathstyles. Eur J Biochem 2004;271:1638-50.
  • 9. Wyllie AH, Morris RG, Smith AL, Dunlop D. Chromatin cleavage in apoptosis: association with condensed chromatin morphology and dependence on macromolecular synthesis. J Pathol 1984;142:67-77.
  • 10. Öktem S, Özhan MH, Özol D. The importance of apoptosis. Toraks Dergisi 2001;2:91-5.
  • 11. CB T. Apoptosis. Lippincott- Raven Publishers, 1999.
  • 12. Ulukaya E, Yilmaztepe A, Akgoz S, et al. The levels of caspase-cleaved cytokeratin 18 are elevated in serum from patients with lung cancer and helpful to predict the survival. Lung Cancer 2007;56:399-404.
  • 13. Smith F. The molecular genetics of keratin disorders. Am J Clin Dermatol 2003;4:347-64.
  • 14. Quinlan RA, Schiller DL, Hatzfeld M, et al. Patterns of expression and organization of cytokeratin intermediate filaments. Ann N Y Acad Sci 1985;455:282-306.
  • 15. Kramer G, Erdal H, Mertens HJ, et al. Differentiation between cell death modes using measurements of different soluble forms of extracellular cytokeratin 18. Cancer Res 2004;64:1751-6.
  • 16. Kronenberger B, Wagner M, Herrmann E, et al. Apoptotic cytokeratin 18 neoepitopes in serum of patients with chronic hepatitis C. J Viral Hepat 2005;12:307-14.
  • 17. Bantel H, Lugering A, Heidemann J, et al. Detection of apoptotic caspase activation in sera from patients with chronic HCV infection is associated with fibrotic liver injury. Hepatology 2004;40:1078-87.
  • 18. European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2017;67:370-98.
  • 19. Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology 2009;50:661-2.
  • 20. McMahon BJ. The natural history of chronic hepatitis B virus infection. Hepatology 2009;49(5 Suppl):S45-55.
  • 21. Kronenberger B, Zeuzem S, Sarrazin C, et al. Dynamics of apoptotic activity during antiviral treatment of patients with chronic hepatitis C. Antivir Ther 2007;12:779-87.
  • 22. Hotchkiss RS, Strasser A, McDunn JE, Swanson PE. Cell death. N Engl J Med 2009;361:1570-83.
  • 23. Farnik H, Lange CM, Hofmann WP, et al Nucleos(t)ide analogue treatment reduces apoptotic activity in patients with chronic hepatitis B. J Clin Virol 2011;52:204-9.
  • 24. Papatheodoridis GV, Hadziyannis E, Tsochatzis E, et al. Serum apoptotic caspase activity as a marker of severity in HBeAg-negative chronic hepatitis B virus infection. Gut 2008;57:500-6.
  • 25. Yilmaz Y, Dolar E, Ulukaya E, et al. Elevated serum levels of caspase-cleaved cytokeratin 18 (CK18-Asp396) in patients with nonalcoholic steatohepatitis and chronic hepatitis C. Med Sci Monit 2009;15:CR189-93.
  • 26. Tabuchi M, Tomioka K, Kawakami T, et al. Serum cytokeratin 18 M30 antigen level and its correlation with nutritional parameters in middle-aged Japanese males with nonalcoholic fatty liver disease (NAFLD). J Nutr Sci Vitaminol (Tokyo) 2010;56:271-8.
There are 26 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Articles
Authors

Mustafa Çelik 0000-0001-8175-2324

Sezgin Vatansever This is me 0000-0002-8413-5353

Altay Kandemir 0000-0002-2918-3811

Belkis Ünsal This is me 0000-0003-2816-9214

Publication Date September 24, 2018
Published in Issue Year 2018 Volume: 17 Issue: 2

Cite

APA Çelik, M., Vatansever, S., Kandemir, A., Ünsal, B. (2018). The Utility of M30 and M65 Antigen Concentration Levels for Predicting Degree of Hepatic Injury in Patients with Chronic Hepatitis B Infection. Akademik Gastroenteroloji Dergisi, 17(2), 45-49. https://doi.org/10.17941/agd.456947

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