Kronik hepatit B enfeksiyonununda hepatik hasar düzeyinin öngörülmesinde M30 ve M65 antijen düzeylerinin etkinliği
Giriş ve Amaç: 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 (p0.05). Hasta grupta yapılan korelasyon analizinde M30-antijen ile aspartat aminotransferaz arasında (r:0.207, p
The utility of M30 and M65 antigen concentration levels for predicting degree of hepatic injury in patients with chronic hepatitis B infection
Background and Aims: We aimed to determine the utility of M30and M65 antigen concentration levels for predicting hepatic injury inchronic hepatitis B disease. Materials and Methods: This study comparedconcentration levels of M30 and M65 antigens between patientswith hepatitis B e-antigen negative chronic hepatitis B and healthysubjects. Furthermore, the correlations between either M30 or M65antigen levels and aspartate aminotransferase, alanine aminotransferase,HBV-DNA, histological activity index and fibrosis were evaluatedin the patient group. Results: A total of 81 subjects were included inthe study; 50 patients with HBeAg negative chronic hepatitis B and31 healthy subjects. The concentration of the M30 antigen was significantlyhigher in the chronic hepatitis B patient group than in thehealthy subject group (p 0.05).Correlation analysis performed in the patient group revealed a significantcorrelation between M30 antigen concentration levels and aspartateaminotransferase levels (r: 0.207, p
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- Ganem D, Prince AM. Hepatitis B virus infection--natural history and
clinical consequences. N Engl J Med 2004;350:1118-29.
- Hoofnagle JH, Doo E, Liang TJ, et al. Management of hepatitis
B: summary of a clinical research workshop. Hepatology
2007;45:1056-75.
- Liaw YF. Prevention and surveillance of hepatitis B virus-related hepatocellular
carcinoma. Semin Liver Dis 2005;25:40-7.
- Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology 2007;45:507-
39.
- 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 tolerance 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.
- Assuncao Guimaraes C and Linden R. Programmed cell
deaths. Apoptosis and alternative deathstyles. Eur J Biochem
2004;271:1638-50.
- 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.
- Öktem S, Özhan MH, Özol D. The importance of apoptosis. Toraks
Dergisi 2001;2:91-5.
- CB T. Apoptosis. Lippincott- Raven Publishers, 1999.
- Ulukaya E, Yilmaztepe A, Akgoz S, et al. The levels of caspasecleaved
cytokeratin 18 are elevated in serum from patients with
lung cancer and helpful to predict the survival. Lung Cancer
2007;56:399-404.
- Smith F. The molecular genetics of keratin disorders. Am J Clin
Dermatol 2003;4:347-64.
- 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.
- 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.
- 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.
- 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.
- 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.
- Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology
2009;50:661-2.
- McMahon BJ. The natural history of chronic hepatitis B virus infection.
Hepatology 2009;49(5 Suppl):S45-55.
- 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.
- Hotchkiss RS, Strasser A, McDunn JE, Swanson PE. Cell death. N
Engl J Med 2009;361:1570-83.
- 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.
- 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.
- 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.
- 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.