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Kronik hepatit b tedavisinde HBsAg ve M30 antijen titre takibinin klinik yararı

Year 2021, Volume: 14 Issue: 2, 380 - 387, 01.04.2021

Zeynep Dündar Ök Mustafa Çelik İsmail Hakkı Akbudak Yüksel Güleryüzlü Halil Yılmaz Mustafa Yılmaz

https://doi.org/10.31362/patd.826929

Abstract

Giriş: Antiviral tedavi öncesi ve sonrası serum HBsAg ve cccDNA düzeyleri ve bu değerlerdeki düşüş oranları arasında pozitif ilişki olduğu bilinmektedir. Serolojik HbsAg seviyesi de cccDNA ile ilişkilendirilmiştir ve serolojik HbsAg, enfekte olmuş hücreleri teşhis etmek için cccDNA'nın yerini alan bir biyobelirteç olarak kabul edilmiştir. M30 antijeni, apoptoz sırasında kaspaz proteinleri tarafından parçalanan CK 18 seviyelerini tespit etmek için kullanılır. Ayrıca KHB hastalığında, apopitoz belirteci olan M30 antijen düzeyleri ile karaciğer hasarı arasında ilişki olduğu gösterilmiştir. Bu çalışmada KHB enfeksiyonu’nun şiddeti ve nucleoz (t)ide analoğu (NA) tedavisine klinik yanıtının değerlendirilmesinde HbsAg ve M30 antijen titre takibinin yararını saptamayı amaçladık.
Gereç ve yöntem: Çalışmaya KHB enfeksiyonuna yönelik oral antiviral tedavi verilen 60 hasta dahil edildi. Tüm hastalarda tedavi başlangıcında saptanan AST, ALT, HBVDNA, HAİ, fibrozis ile HbsAg ve M30 antijen düzeyleri arasındaki korelasyon değerlendirildi. Tedavi başlangıcı ve tedavinin 6. ayında saptanan AST, ALT, HBVDNA, HbsAg ve M30 antijen düzeyleri karşılaştırıldı. Tedavi ile bu değerlerde saptanan düşüş oranları değerlendirildi. Ayrıca hastalar aldıkları tedaviye göre Lamivudin ve Tenofovir alanlar olarak iki gruba ayrıldı. İki grup tedavi ile AST, ALT, HBVDNA, HbsAg ve M30 antijen düzeylerindeki düşüş oranları açısından karşılaştırıldı. HbsAg ve M30 antijen seviyelerinin tedavi sonrası azalma oranı açısından iki grup da karşılaştırıldı.
Bulgular: Tedavi başlangıcında saptanan AST, ALT, HBVDNA düzeyleri ile HbsAg ve M30 antijen arasında pozitif korelasyon saptandı (p<0,001). HAİ, Fibrozis dereceleri ile HbsAg arasında anlamlı ilişki saptanmazken (p>0,05), HAİ, Fibrozis dereceleri ile M30 antijen düzeyleri arasında pozitif korelasyon saptandı (p<0,01). Tedavi verilen tüm hastalarda tedavinin 6. ayında saptanan AST, ALT, HBVDNA, HbsAg ve M30 antijen düzeylerinde, tedavi başlangıcına göre istatistiksel olarak anlamlı azalma olduğu görüldü (p<0,001). Lamivudin ve Tenofovir grupları arasında HBVDNA düzeylerindeki düşüş oranları açısından anlamlı fark saptanmadı (p>0,05). Bununla birlikte tedavi ile HbsAg ve M30 antigen düzeylerindeki düşüş oranları tenofovir grubunda lamivudin grubuna göre istatistiksel olarak anlamlı düzeyde daha yüksek saptandı (p<0,001).
Sonuç: HbsAg ve M30 antijen düzeyi ölçümü KHB enfeksiyonu’nun şiddetinin ve tedavi etkinliğinin değerlendirilmesinde kullanılabilir. Tenofovir ile HbsAg ve M30 antijen düzeylerinde düşüşün lamivudin grubuna göre daha belirgin olması, bize KHB enfeksiyonunun en etkin ilaç seçeneği ile tedavisinin hücre ölümü-apoptozisin önüne geçilmesinde etkili olacağını gösterdi. Bu sebeple sadece ALT ve HBVDNA sonuçlarının takibine göre düşük direç bariyeri olan oral antivirallerin kullanımında ısrar edilmesinin yanlış olduğu kanaatindeyiz.

Keywords

Hepatit B enfeksiyonu M30 antijen HBsAg nükleoz(t)id analogları oral antiviral tedavi

References

  • Lavanchy D. Hepatitis B epidemiology, disease burden treatment and emerging prevention and control mesaures. J Viralhepat 2004; 11(2):97-107.
  • Liang TJ. Hepatitis B: Thevirusanddisease. Hepatology 2009; 49(5 suppl):S13-21.
  • European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of chronic hepatitis B. J Hepatol 2009;50:227-242).
  • Cornberg M, Honer Zu Siederdissen C. HBsAg seroclearance with NUCs: rare but important. Gut 2014;63:1208-1209.
  • Brunetto MR. A new role for an old marker, HBsAg. J Hepatol 2010;52:475-477.
  • Sung JJ, Wong ML, Bowden S, Liew CT, Hui Ay, Wong VW, et al. Intrahepatic hepatitis B virus covalently closed circular DNA can be a predictor of sustained response to therapy. Gastroentereology 2005;128:1890-1897. Chan HL, Wong VW, Tse AM, Tse CH, Chim AM, Chan HY, et al. Serum hepatitis B surface antigen quantitatin can reflect hepatitis B virus in the liver and predict treatment response. Clin Gastroenterol Hepatol 2007;5:1462-1468.
  • Werle-Lapostolle B, Bowden S , Locarnini S, Wursthorn K, Petersen J, Lau G, et al. Persistence of cccDNA during the natural history of chronic hepatitis B and decline during adefovir dipivoxil therapy. Gastroenterology 2004;126:1750-1758.
  • Manesis EK, Schina M, Le Gal F, Agelopoulou O, Papaioannou C, Kalligeros C, et al. Quantitatvive analysis of hepatitis D virus RNA and hepatitis B surface antigen serum levels in chronic delta hepatitis improves treatment monitoring. Antivir Ther 2007;12:381-388.
  • Manesis EK, Hadziyannis ES, Angelopoulou OP, Hadziyannis SJ. Prediction of treatment-related HBsAg loss in HBeAg negative chronic hepatitis B: a clue from serum HBsAg levels. Antivir Ther 2007;12:73-82 Fischer R, Baumert T, Blum HE. Hepatitis C virus infection and apoptosis. World J Gastroenterol 2007;13:4865-72.
  • Lapierre P, Beland K, Alvarez F. Pathogenesis of autoimmune hepatitis: from break of talerance to immune-mediated hepatocyte apoptosis. Transl Res 2007;149:107-13.
  • Day CP. Apoptosis in alcoholic hepatitis:a novel therapeutic target. J Hepatol 2001;34:330-3.
  • McMahon BJ. The natural history of chronic hepatitis B virüs infection. Hepatology 2009;49:S45-S55.
  • Kronenberger B,Zeuzem S, Sarrazin C, Mihm U,von Wagner M, Hofmann WP, et al. Dynamics of apoptotic activity during antiviral treatment of patients with chronic hepatitis C. Antivir Ther 2007;12:779-87.
  • Kronenberger B, Wagner M, Hermann E, Mihm U, Piiper A, Sarrazin C, et al. Apoptotic cytokeratin 18 neoepitopes in serum of patients with chronic hepatitis C. J Viral Hepat 2005;12:307-314.
  • Bantel H, LugeringA, Heidemann j et al. Detection of apopitotic caspase activation in sera from patients with chronic HCV infection is associated with fibrotic liver injury. Hepatology 2004;40:1078-1087.
  • Papatheodoridis GV, Hadziyannis E, Tsochatzis E, Chrysanthos N, Georgiou A, Kafiri G, et al. Serum apoptotic caspase activity as a marker of severity in HBeAg-negative chronic hepatitis B virus infection. Gut 2008;57:500–6.
  • Lok AS, McMohan BJ. Practice Guidelines Committee, American Assocation for the Study of Liver Diseases.Chronic Hepatitis B. Hepatology 2009;50;601-2.
  • Feldstein, A. E. et al. Cytokeratin-18 fragment levels as noninvasive biomarkers for nonalcoholic steatohepatitis: a multicenter validation study. Hepatology (Baltimore, Md.) 2009;50:1072–1078 .
  • Rutherford, A. et al. Development of an accurate index for predicting outcomes of patients with acute liver failure. Gastroenterology 2012;143:1237–1243.
  • Jazwinski AB, Thompson AJ, Clark PJ, et al. Elevated serum CK18 levels in chronic hepatitis C patients are associated with advanced fibrosis but not steatosis. J Viral Hepat 2012; 19: 278–82.
  • Parfieniuk-Kowerda A, Lapinski TW, Rogalska-Plonska M, Swiderska M, Panasiuk A, Jaroszewicz J, Flisiak R. Serum cytochrome c and m30-neoepitope of cytokeratin-18 in chronic hepatitis C. Liver International 2014;34:544-50.
  • Cao Z, Li F, Xiang X, Liu K, Liu Y, Tang W, et al. Circulating cell death biomarker: good candidates of prognostic indicator for patients with hepatitis B virus related acute-on chronic liver failure. Sci Rep 2015;18:5.
  • EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol 2012;57:167-185.
  • Colombo M. Does chemotherapy prevent HBV-related hepatocellular carcinoma? Cons Dig Liver Dis 2010;42(Suppl. 3):S298–301.
  • Liaw YF. Impact of hepatitis B therapy on the long-term outcome of liver disease.Liver Int 2011;31(Suppl. 1):117–21.
  • Takkenberg RB, Zaaijer HL, Molenkamp R, Menting S, Terpstra V, Weegink CJ, et al. Validation of a sensitive and specific real-time PCR for detection and quantitation of hepatitis B virus covalently closed circular DNA in plasma of chronic hepatitis B patients. J Med Virol 2009;81:988–95.
  • Suh SJ, Bae SI, Kim JH, Kang K, Yeon JE, Byun KS. Clinical implications of the titer of serum hepatitis B surface antigen during the natural history of hepatitis B virus infection. J Med Virol 2014;86:117-23.
  • Park H, Lee JM, Seo JH, Kim HS, Ahn SH, Kim do Y, et al. Predictive value of HbsAg quantification for determining the clinical course of genotype C HBeAg-negative carriers. Liver Int 2012;32:796-802.
  • Farnika H, Langea CM, Hofmanna WP, Bergerc A, Allwinnc R, Welkera MW, et al. Nucleos(t)ide analogue treatment reduces apoptotic activity in patients with chronic hepatitis B. Journal of Clinical Virology 2011;52:204– 209.
  • Jochum, C. et al. Hepatitis B-associated acute liver failure: immediate treatment with entecavir inhibits hepatitis B virüs replication and potentially its sequelae. Digestion 2009;80:235–240.
  • Giannousis, I. P., Manolakopoulos, S. G., Hadziyannis, E., Georgiou, A. & Papatheodoridis, G. V. Changes of serum levels of keratin-18 fragments in hepatitis B e antigen-negative chronic hepatitis B patients under oral antiviral therapy. Antiviral therapy 2011;16:505–514.

Year 2021, Volume: 14 Issue: 2, 380 - 387, 01.04.2021

Zeynep Dündar Ök Mustafa Çelik İsmail Hakkı Akbudak Yüksel Güleryüzlü Halil Yılmaz Mustafa Yılmaz

https://doi.org/10.31362/patd.826929

Abstract

References

  • Lavanchy D. Hepatitis B epidemiology, disease burden treatment and emerging prevention and control mesaures. J Viralhepat 2004; 11(2):97-107.
  • Liang TJ. Hepatitis B: Thevirusanddisease. Hepatology 2009; 49(5 suppl):S13-21.
  • European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of chronic hepatitis B. J Hepatol 2009;50:227-242).
  • Cornberg M, Honer Zu Siederdissen C. HBsAg seroclearance with NUCs: rare but important. Gut 2014;63:1208-1209.
  • Brunetto MR. A new role for an old marker, HBsAg. J Hepatol 2010;52:475-477.
  • Sung JJ, Wong ML, Bowden S, Liew CT, Hui Ay, Wong VW, et al. Intrahepatic hepatitis B virus covalently closed circular DNA can be a predictor of sustained response to therapy. Gastroentereology 2005;128:1890-1897. Chan HL, Wong VW, Tse AM, Tse CH, Chim AM, Chan HY, et al. Serum hepatitis B surface antigen quantitatin can reflect hepatitis B virus in the liver and predict treatment response. Clin Gastroenterol Hepatol 2007;5:1462-1468.
  • Werle-Lapostolle B, Bowden S , Locarnini S, Wursthorn K, Petersen J, Lau G, et al. Persistence of cccDNA during the natural history of chronic hepatitis B and decline during adefovir dipivoxil therapy. Gastroenterology 2004;126:1750-1758.
  • Manesis EK, Schina M, Le Gal F, Agelopoulou O, Papaioannou C, Kalligeros C, et al. Quantitatvive analysis of hepatitis D virus RNA and hepatitis B surface antigen serum levels in chronic delta hepatitis improves treatment monitoring. Antivir Ther 2007;12:381-388.
  • Manesis EK, Hadziyannis ES, Angelopoulou OP, Hadziyannis SJ. Prediction of treatment-related HBsAg loss in HBeAg negative chronic hepatitis B: a clue from serum HBsAg levels. Antivir Ther 2007;12:73-82 Fischer R, Baumert T, Blum HE. Hepatitis C virus infection and apoptosis. World J Gastroenterol 2007;13:4865-72.
  • Lapierre P, Beland K, Alvarez F. Pathogenesis of autoimmune hepatitis: from break of talerance to immune-mediated hepatocyte apoptosis. Transl Res 2007;149:107-13.
  • Day CP. Apoptosis in alcoholic hepatitis:a novel therapeutic target. J Hepatol 2001;34:330-3.
  • McMahon BJ. The natural history of chronic hepatitis B virüs infection. Hepatology 2009;49:S45-S55.
  • Kronenberger B,Zeuzem S, Sarrazin C, Mihm U,von Wagner M, Hofmann WP, et al. Dynamics of apoptotic activity during antiviral treatment of patients with chronic hepatitis C. Antivir Ther 2007;12:779-87.
  • Kronenberger B, Wagner M, Hermann E, Mihm U, Piiper A, Sarrazin C, et al. Apoptotic cytokeratin 18 neoepitopes in serum of patients with chronic hepatitis C. J Viral Hepat 2005;12:307-314.
  • Bantel H, LugeringA, Heidemann j et al. Detection of apopitotic caspase activation in sera from patients with chronic HCV infection is associated with fibrotic liver injury. Hepatology 2004;40:1078-1087.
  • Papatheodoridis GV, Hadziyannis E, Tsochatzis E, Chrysanthos N, Georgiou A, Kafiri G, et al. Serum apoptotic caspase activity as a marker of severity in HBeAg-negative chronic hepatitis B virus infection. Gut 2008;57:500–6.
  • Lok AS, McMohan BJ. Practice Guidelines Committee, American Assocation for the Study of Liver Diseases.Chronic Hepatitis B. Hepatology 2009;50;601-2.
  • Feldstein, A. E. et al. Cytokeratin-18 fragment levels as noninvasive biomarkers for nonalcoholic steatohepatitis: a multicenter validation study. Hepatology (Baltimore, Md.) 2009;50:1072–1078 .
  • Rutherford, A. et al. Development of an accurate index for predicting outcomes of patients with acute liver failure. Gastroenterology 2012;143:1237–1243.
  • Jazwinski AB, Thompson AJ, Clark PJ, et al. Elevated serum CK18 levels in chronic hepatitis C patients are associated with advanced fibrosis but not steatosis. J Viral Hepat 2012; 19: 278–82.
  • Parfieniuk-Kowerda A, Lapinski TW, Rogalska-Plonska M, Swiderska M, Panasiuk A, Jaroszewicz J, Flisiak R. Serum cytochrome c and m30-neoepitope of cytokeratin-18 in chronic hepatitis C. Liver International 2014;34:544-50.
  • Cao Z, Li F, Xiang X, Liu K, Liu Y, Tang W, et al. Circulating cell death biomarker: good candidates of prognostic indicator for patients with hepatitis B virus related acute-on chronic liver failure. Sci Rep 2015;18:5.
  • EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol 2012;57:167-185.
  • Colombo M. Does chemotherapy prevent HBV-related hepatocellular carcinoma? Cons Dig Liver Dis 2010;42(Suppl. 3):S298–301.
  • Liaw YF. Impact of hepatitis B therapy on the long-term outcome of liver disease.Liver Int 2011;31(Suppl. 1):117–21.
  • Takkenberg RB, Zaaijer HL, Molenkamp R, Menting S, Terpstra V, Weegink CJ, et al. Validation of a sensitive and specific real-time PCR for detection and quantitation of hepatitis B virus covalently closed circular DNA in plasma of chronic hepatitis B patients. J Med Virol 2009;81:988–95.
  • Suh SJ, Bae SI, Kim JH, Kang K, Yeon JE, Byun KS. Clinical implications of the titer of serum hepatitis B surface antigen during the natural history of hepatitis B virus infection. J Med Virol 2014;86:117-23.
  • Park H, Lee JM, Seo JH, Kim HS, Ahn SH, Kim do Y, et al. Predictive value of HbsAg quantification for determining the clinical course of genotype C HBeAg-negative carriers. Liver Int 2012;32:796-802.
  • Farnika H, Langea CM, Hofmanna WP, Bergerc A, Allwinnc R, Welkera MW, et al. Nucleos(t)ide analogue treatment reduces apoptotic activity in patients with chronic hepatitis B. Journal of Clinical Virology 2011;52:204– 209.
  • Jochum, C. et al. Hepatitis B-associated acute liver failure: immediate treatment with entecavir inhibits hepatitis B virüs replication and potentially its sequelae. Digestion 2009;80:235–240.
  • Giannousis, I. P., Manolakopoulos, S. G., Hadziyannis, E., Georgiou, A. & Papatheodoridis, G. V. Changes of serum levels of keratin-18 fragments in hepatitis B e antigen-negative chronic hepatitis B patients under oral antiviral therapy. Antiviral therapy 2011;16:505–514.
There are 31 citations in total.

Details

Primary Language Turkish
Subjects Gastroenterology and Hepatology
Journal Section Research Article
Authors

Zeynep Dündar Ök 0000-0003-0925-2098

Mustafa Çelik 0000-0001-8175-2324

İsmail Hakkı Akbudak 0000-0002-3716-9243

Yüksel Güleryüzlü This is me 0000-0002-2522-1550

Halil Yılmaz 0000-0002-3191-2171

Mustafa Yılmaz 0000-0003-4541-172X

Publication Date April 1, 2021
Submission Date November 18, 2020
Acceptance Date January 18, 2021
Published in Issue Year 2021 Volume: 14 Issue: 2

Cite

APA Dündar Ök, Z., Çelik, M., Akbudak, İ. H., Güleryüzlü, Y., et al. (2021). Kronik hepatit b tedavisinde HBsAg ve M30 antijen titre takibinin klinik yararı. Pamukkale Medical Journal, 14(2), 380-387. https://doi.org/10.31362/patd.826929
AMA Dündar Ök Z, Çelik M, Akbudak İH, Güleryüzlü Y, Yılmaz H, Yılmaz M. Kronik hepatit b tedavisinde HBsAg ve M30 antijen titre takibinin klinik yararı. Pam Med J. April 2021;14(2):380-387. doi:10.31362/patd.826929
Chicago Dündar Ök, Zeynep, Mustafa Çelik, İsmail Hakkı Akbudak, Yüksel Güleryüzlü, Halil Yılmaz, and Mustafa Yılmaz. “Kronik Hepatit B Tedavisinde HBsAg Ve M30 Antijen Titre Takibinin Klinik Yararı”. Pamukkale Medical Journal 14, no. 2 (April 2021): 380-87. https://doi.org/10.31362/patd.826929.
EndNote Dündar Ök Z, Çelik M, Akbudak İH, Güleryüzlü Y, Yılmaz H, Yılmaz M (April 1, 2021) Kronik hepatit b tedavisinde HBsAg ve M30 antijen titre takibinin klinik yararı. Pamukkale Medical Journal 14 2 380–387.
IEEE Z. Dündar Ök, M. Çelik, İ. H. Akbudak, Y. Güleryüzlü, H. Yılmaz, and M. Yılmaz, “Kronik hepatit b tedavisinde HBsAg ve M30 antijen titre takibinin klinik yararı”, Pam Med J, vol. 14, no. 2, pp. 380–387, 2021, doi: 10.31362/patd.826929.
ISNAD Dündar Ök, Zeynep et al. “Kronik Hepatit B Tedavisinde HBsAg Ve M30 Antijen Titre Takibinin Klinik Yararı”. Pamukkale Medical Journal 14/2 (April 2021), 380-387. https://doi.org/10.31362/patd.826929.
JAMA Dündar Ök Z, Çelik M, Akbudak İH, Güleryüzlü Y, Yılmaz H, Yılmaz M. Kronik hepatit b tedavisinde HBsAg ve M30 antijen titre takibinin klinik yararı. Pam Med J. 2021;14:380–387.
MLA Dündar Ök, Zeynep et al. “Kronik Hepatit B Tedavisinde HBsAg Ve M30 Antijen Titre Takibinin Klinik Yararı”. Pamukkale Medical Journal, vol. 14, no. 2, 2021, pp. 380-7, doi:10.31362/patd.826929.
Vancouver Dündar Ök Z, Çelik M, Akbudak İH, Güleryüzlü Y, Yılmaz H, Yılmaz M. Kronik hepatit b tedavisinde HBsAg ve M30 antijen titre takibinin klinik yararı. Pam Med J. 2021;14(2):380-7.

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