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Hepatit B ve Hepatit C Nedenli Sirotik Karaciğer Metaryalinde Sinyal transdüserleri ve transkripsiyon aktivatörleri, İnterlökin-6, İnterlökin-10 Pozitifliğinin Antiviral Tedavi ile İlişkisi

Year 2018, Volume: 45 Issue: 2, 187 - 194, 15.06.2018
https://doi.org/10.5798/dicletip.424993

Abstract

Giriş: Viral hepatit infeksiyonlarına bağlı terminal dönem karaciğer hastalığı önemli bir sağlık sorunudur. Bu çalışmada antiviral tedavi almış terminal dönem karaciğer yetmezliği sebebiyle karaciğer nakli yapılan hepatektomi materyallerinde STAT-1,2,3,5,5a,5b, IL-6 ve IL-10 ekspresyonlarının karşılaştırılması amaçlandı. Yöntemler: viral hepatitler (HCV ve HBV)’e bağlı kronik karaciğer yetmezliği nedeni ile karaciğer transplantasyonu yapılan 45 olgu çalışmaya dâhil edildi. Çalışmamızda hastalar karaciğer transplantasyonu öncesi almış oldukları ilaç tedavilerine göre 3 gruba ayrıldı. Grup A: Lamuvidine, Grup B: Adefovir, Grup C: İnterferon veya interferon + ribavidin. Sonuçlar: Çalışma popülasyonunda 9 (%20) hasta kadındı ve 36 (%80) erkek idi. Yaş ortalaması 45.7 (29-69) idi. STAT-2, -3 ve IL-6 ekspresyonu Grup A'da hepatositlerde anlamlı olarak daha yüksekti (p <0.05). Sonuç: Yüksek STAT-3, yüksek IL-6 ve düşük STAT-1 ekspresyonu, optimumhepatositrejenerasyonu ve karaciğer metabolik fonksiyonu ile ilişkiliydi. Bu bağlamda, lamivudin, bu çalışmada en etkili ilaç olmuştur.

References

  • 1. Curry MP, Chopra S. Acute viral hepatitis. İn: Mandell GL, Bennet JE, Dolin R, editors. Principles and practice of infectious diseases, 6th ed, Churchill Livingstone, Philadelphia 2005: 1426-41.
  • 2. Thomson BJ, Finch RG. Hepatitis C virus infection. Clin Microbiol İnfect 2005; 11: 86-94.
  • 3. Guan S.H, Lu M, Grünewald P et al. Interferon-α response in chronic hepatitis B- transfected HepG2.2.15 cells is partially restored by lamivudine treatment. World Journal of Gastroenterology 2007; 13: 228-35.
  • 4. Dogan L, Güç D. Sinyal İletimi Mekanizmaları ve Kanser. Hacettepe Tıp Dergisi 2004; 35: 34-42.
  • 5. Castell JV, Gomez MJ. IL-6 is a major regulator of the acute phase protein synthesis in human hepatocytes. FEBS LETT1989; 237-42.
  • 6. Gao B. Cytokines, STATs and Liver Disease. Cellüler&Moleküler İmmünology 2005 Volume 2: 92-100.
  • 7. Tiberio G.A.M, Tiberio L, Benetti A et al.IL-6 Promotes Compensatory Liver Regeneration in cirhotic Rat after partial hepatectomy. Cytokine 2008; 42: 372-8.
  • 8. Yano Y, Seo Y, Hayashi H et al. Factors associated with the decrease in hepatitis B surface antigen titers following interferon therapy in patients with chronic hepatitis B: Is interferon and adefovir combination therapy effective? Biomed Rep. Sep 2017; 7: 257-62.
  • 9. Hynicka LM, Yunker N, Patel PH. A review of oral antiretroviral therapy for the treatment of chronic hepatitis B. Ann Pharmacother 2010; 44: 1271-86.
  • 10. Lam YF, Yuen MF, Seto WK et al. Current antiviral therapy of chronic hepatitis B: Efficacy and safety. Curr Hepat Rep 2011; 10: 235 43.
  • 11. Shi Y, Wu YH, Shu ZY et al. Interferon and lamivudine combination therapy versus lamivudine monotherapy for hepatitis B e antigen negative hepatitis B treatment: A meta analysis of randomized controlled trials. Hepatobiliary Pancreat Dis Int 2010; 9: 462 72.
  • 12. Huang R, Hao Y, Zhang J et al. Interferon alpha plus adefovir combination therapy versus interferon alpha monotherapy for chronic hepatitis B treatment: A meta analysis. Hepatol Res 2013; 43: 1040 51.
  • 13. Liaw YF, Kao JH, Piratvisuth T et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update. Hepatol Int. 2012 Jun;6: 531-61.
  • 14. Waris G, Sıddıqui A; J. Biosci. Regulatory mechanisms of viral hepatitis B and C. Journal of Biosciences 2003; 28: 311-21.
  • 15. Siebler J, Protzer U, Wirtz S et al. Overexspression of STAT-1 by adenoviral gene transfer does not inhibit hepatitis B virus replication. European Journal of Gastroenterology & Hepatology 2006; 18: 167-74.
  • 16. Waris G, Sıddıqui A. Interaction between STAT-3 and HNF- 3 leads to the activation of liver-specific hepatitis B virus enhancer 1 function. Journal of Virology 2002; 76: 2721-9.
  • 17. Cui Y, Hosui A, Sun R et al. Loss of signal transducer and activator of transcription 5 leads to Hepatosteatosis and impaired liver regeneration. Hepatology 2007; 46: 504-13.
  • 18. Stärkel P, De Saeger C, Leclercq I et al. Role of signal transducer and activator of transcription 3 in liver fibrosis progression in chronic hepatitis C-infected patients. Laboratory investigation 2007; 87: 173–81
  • 19. Bautista D, Bermudez-Silva F.J, Lasarte J.J et al. Liver ekspression of proteins controlling interferon- mediated signaling as predictive factors in the response to therapy in patients with hepatitis C virus infection. Journal of Pathology 2007; 213: 347-55.
  • 20. Moran DM, Mattocks MA, Cahill PA et al. Interleukin-6 mediates G(0)/G(1) growth arrest in hepatocellular carcinoma through a STAT 3-dependent pathway. Journal of Surgical Research 2008; 147: 23-33.
  • 21. Yilmaz S, Kirimlioglu V, Kirimlioglu H et al. Effects of nucleoside analogues on liver regeneration 70% partially hepatectomized rats. Transplant Proc 2006; 38: 568-70.
  • 22. Henninghausen L, Robinson G.W. Interpretation of cytokine signaling through the transcription factors STAT 5A and STAT 5B. Genes Dev 2008; 22: 711-21.

Association of signal transducer and activator of transcription, interleukin-6, and interleukin-10 positivity with antiviral treatment in cirrhotic liver samples from patients with the hepatitis B or C virus

Year 2018, Volume: 45 Issue: 2, 187 - 194, 15.06.2018
https://doi.org/10.5798/dicletip.424993

Abstract

Objective: Terminal liver disease due to viral hepatitis infections is an important health problem. This study aimed to compare the expression of members of the signal transducer and activator of transcription (STAT) family (STAT-1, -2, -3, -5a, and -5b) and interleukin (IL)-6 and IL-10 in hepatectomy material from patients who received antiviral treatment and underwent a liver transplantation due to terminal liver failure. Methods: The study consisted of 45 patients who underwent a liver transplantation due to chronic liver failure associated with viral hepatitis (hepatitis C virus [HCV] or hepatitis B virus [HBV]). The patients were divided into three groups according to the drug treatments they received prior to the liver transplantation: Group A: lamivudine, Group B: adefovir, and Group C: interferon or interferon + ribavirin. Results: In the study population, 9 (20%) patients were females and 36 (80%) were males. The mean age was 45.7 (29–69) years. STAT-2, -3, and IL-6 expression were significantly higher in hepatocytes in Group A (p<0.05). Conclusion: High STAT-3, high IL-6, and low STAT-1 expression were associated with optimum hepatocyte regeneration and liver metabolic function. In this regard, lamivudine was the most effective drug in the present study. 

References

  • 1. Curry MP, Chopra S. Acute viral hepatitis. İn: Mandell GL, Bennet JE, Dolin R, editors. Principles and practice of infectious diseases, 6th ed, Churchill Livingstone, Philadelphia 2005: 1426-41.
  • 2. Thomson BJ, Finch RG. Hepatitis C virus infection. Clin Microbiol İnfect 2005; 11: 86-94.
  • 3. Guan S.H, Lu M, Grünewald P et al. Interferon-α response in chronic hepatitis B- transfected HepG2.2.15 cells is partially restored by lamivudine treatment. World Journal of Gastroenterology 2007; 13: 228-35.
  • 4. Dogan L, Güç D. Sinyal İletimi Mekanizmaları ve Kanser. Hacettepe Tıp Dergisi 2004; 35: 34-42.
  • 5. Castell JV, Gomez MJ. IL-6 is a major regulator of the acute phase protein synthesis in human hepatocytes. FEBS LETT1989; 237-42.
  • 6. Gao B. Cytokines, STATs and Liver Disease. Cellüler&Moleküler İmmünology 2005 Volume 2: 92-100.
  • 7. Tiberio G.A.M, Tiberio L, Benetti A et al.IL-6 Promotes Compensatory Liver Regeneration in cirhotic Rat after partial hepatectomy. Cytokine 2008; 42: 372-8.
  • 8. Yano Y, Seo Y, Hayashi H et al. Factors associated with the decrease in hepatitis B surface antigen titers following interferon therapy in patients with chronic hepatitis B: Is interferon and adefovir combination therapy effective? Biomed Rep. Sep 2017; 7: 257-62.
  • 9. Hynicka LM, Yunker N, Patel PH. A review of oral antiretroviral therapy for the treatment of chronic hepatitis B. Ann Pharmacother 2010; 44: 1271-86.
  • 10. Lam YF, Yuen MF, Seto WK et al. Current antiviral therapy of chronic hepatitis B: Efficacy and safety. Curr Hepat Rep 2011; 10: 235 43.
  • 11. Shi Y, Wu YH, Shu ZY et al. Interferon and lamivudine combination therapy versus lamivudine monotherapy for hepatitis B e antigen negative hepatitis B treatment: A meta analysis of randomized controlled trials. Hepatobiliary Pancreat Dis Int 2010; 9: 462 72.
  • 12. Huang R, Hao Y, Zhang J et al. Interferon alpha plus adefovir combination therapy versus interferon alpha monotherapy for chronic hepatitis B treatment: A meta analysis. Hepatol Res 2013; 43: 1040 51.
  • 13. Liaw YF, Kao JH, Piratvisuth T et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update. Hepatol Int. 2012 Jun;6: 531-61.
  • 14. Waris G, Sıddıqui A; J. Biosci. Regulatory mechanisms of viral hepatitis B and C. Journal of Biosciences 2003; 28: 311-21.
  • 15. Siebler J, Protzer U, Wirtz S et al. Overexspression of STAT-1 by adenoviral gene transfer does not inhibit hepatitis B virus replication. European Journal of Gastroenterology & Hepatology 2006; 18: 167-74.
  • 16. Waris G, Sıddıqui A. Interaction between STAT-3 and HNF- 3 leads to the activation of liver-specific hepatitis B virus enhancer 1 function. Journal of Virology 2002; 76: 2721-9.
  • 17. Cui Y, Hosui A, Sun R et al. Loss of signal transducer and activator of transcription 5 leads to Hepatosteatosis and impaired liver regeneration. Hepatology 2007; 46: 504-13.
  • 18. Stärkel P, De Saeger C, Leclercq I et al. Role of signal transducer and activator of transcription 3 in liver fibrosis progression in chronic hepatitis C-infected patients. Laboratory investigation 2007; 87: 173–81
  • 19. Bautista D, Bermudez-Silva F.J, Lasarte J.J et al. Liver ekspression of proteins controlling interferon- mediated signaling as predictive factors in the response to therapy in patients with hepatitis C virus infection. Journal of Pathology 2007; 213: 347-55.
  • 20. Moran DM, Mattocks MA, Cahill PA et al. Interleukin-6 mediates G(0)/G(1) growth arrest in hepatocellular carcinoma through a STAT 3-dependent pathway. Journal of Surgical Research 2008; 147: 23-33.
  • 21. Yilmaz S, Kirimlioglu V, Kirimlioglu H et al. Effects of nucleoside analogues on liver regeneration 70% partially hepatectomized rats. Transplant Proc 2006; 38: 568-70.
  • 22. Henninghausen L, Robinson G.W. Interpretation of cytokine signaling through the transcription factors STAT 5A and STAT 5B. Genes Dev 2008; 22: 711-21.
There are 22 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Research Articles
Authors

Faik Tatlı 0000-0002-7488-1854

Saime Hale Kırımlıoğlu This is me 0000-0002-2968-2610

Sezai Yılmaz This is me 0000-0002-8044-0297

Orhan Gözeneli This is me 0000-0002-3368-0917

Cüneyt Kayaalp This is me 0000-0003-4657-2998

Melih Karıncaoğlu This is me 0000-0002-9727-5128

Abuzer Dirican This is me 0000-0002-8647-3268

Bora Barut This is me 0000-0001-9489-5973

Vedat Kırımlıoğlu This is me 0000-0002-7488-1854

Publication Date June 15, 2018
Submission Date May 18, 2018
Published in Issue Year 2018 Volume: 45 Issue: 2

Cite

APA Tatlı, F., Kırımlıoğlu, S. H., Yılmaz, S., Gözeneli, O., et al. (2018). Association of signal transducer and activator of transcription, interleukin-6, and interleukin-10 positivity with antiviral treatment in cirrhotic liver samples from patients with the hepatitis B or C virus. Dicle Medical Journal, 45(2), 187-194. https://doi.org/10.5798/dicletip.424993
AMA Tatlı F, Kırımlıoğlu SH, Yılmaz S, Gözeneli O, Kayaalp C, Karıncaoğlu M, Dirican A, Barut B, Kırımlıoğlu V. Association of signal transducer and activator of transcription, interleukin-6, and interleukin-10 positivity with antiviral treatment in cirrhotic liver samples from patients with the hepatitis B or C virus. diclemedj. June 2018;45(2):187-194. doi:10.5798/dicletip.424993
Chicago Tatlı, Faik, Saime Hale Kırımlıoğlu, Sezai Yılmaz, Orhan Gözeneli, Cüneyt Kayaalp, Melih Karıncaoğlu, Abuzer Dirican, Bora Barut, and Vedat Kırımlıoğlu. “Association of Signal Transducer and Activator of Transcription, Interleukin-6, and Interleukin-10 Positivity With Antiviral Treatment in Cirrhotic Liver Samples from Patients With the Hepatitis B or C Virus”. Dicle Medical Journal 45, no. 2 (June 2018): 187-94. https://doi.org/10.5798/dicletip.424993.
EndNote Tatlı F, Kırımlıoğlu SH, Yılmaz S, Gözeneli O, Kayaalp C, Karıncaoğlu M, Dirican A, Barut B, Kırımlıoğlu V (June 1, 2018) Association of signal transducer and activator of transcription, interleukin-6, and interleukin-10 positivity with antiviral treatment in cirrhotic liver samples from patients with the hepatitis B or C virus. Dicle Medical Journal 45 2 187–194.
IEEE F. Tatlı, S. H. Kırımlıoğlu, S. Yılmaz, O. Gözeneli, C. Kayaalp, M. Karıncaoğlu, A. Dirican, B. Barut, and V. Kırımlıoğlu, “Association of signal transducer and activator of transcription, interleukin-6, and interleukin-10 positivity with antiviral treatment in cirrhotic liver samples from patients with the hepatitis B or C virus”, diclemedj, vol. 45, no. 2, pp. 187–194, 2018, doi: 10.5798/dicletip.424993.
ISNAD Tatlı, Faik et al. “Association of Signal Transducer and Activator of Transcription, Interleukin-6, and Interleukin-10 Positivity With Antiviral Treatment in Cirrhotic Liver Samples from Patients With the Hepatitis B or C Virus”. Dicle Medical Journal 45/2 (June 2018), 187-194. https://doi.org/10.5798/dicletip.424993.
JAMA Tatlı F, Kırımlıoğlu SH, Yılmaz S, Gözeneli O, Kayaalp C, Karıncaoğlu M, Dirican A, Barut B, Kırımlıoğlu V. Association of signal transducer and activator of transcription, interleukin-6, and interleukin-10 positivity with antiviral treatment in cirrhotic liver samples from patients with the hepatitis B or C virus. diclemedj. 2018;45:187–194.
MLA Tatlı, Faik et al. “Association of Signal Transducer and Activator of Transcription, Interleukin-6, and Interleukin-10 Positivity With Antiviral Treatment in Cirrhotic Liver Samples from Patients With the Hepatitis B or C Virus”. Dicle Medical Journal, vol. 45, no. 2, 2018, pp. 187-94, doi:10.5798/dicletip.424993.
Vancouver Tatlı F, Kırımlıoğlu SH, Yılmaz S, Gözeneli O, Kayaalp C, Karıncaoğlu M, Dirican A, Barut B, Kırımlıoğlu V. Association of signal transducer and activator of transcription, interleukin-6, and interleukin-10 positivity with antiviral treatment in cirrhotic liver samples from patients with the hepatitis B or C virus. diclemedj. 2018;45(2):187-94.