CURRENT VIEWS ON LIVER FIBROSIS AND ITS MARKERS


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

The review presents current views on the mechanisms responsible for the development of liver fibrosis, deals with the instrumental and laboratory methods for its diagnosis, and gives a detailed description of the most important serum biomarkers. It also shows the relevance and clinical importance of estimating the direct and indirect serum markers of fibrogenesis in chronic diffuse liver diseases of various etiologies. The role of detection of the serum biomarkers is shown in the early diagnosis of liver fibrosis and its progression and in the prediction of fatal complications on the basis of numerous clinical and experimental studies described in the Russian and foreign literature over the past decades. Considering the fact that the results of the performed investigations remain quite controversial and each of the given markers by itself is of no high predictive value; and, as of now, further investigation of the significance of serum markers remains currently relevant to predict liver fibrosis in the outcome of chronic hepatitis of various etiologies.

Full Text

Restricted Access

About the authors

I. V SEMENOVA

Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Welfare

Email: Irinasemenova07@rambler.ru
Moscow

Zhanna B. PONEZHEVA

Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Welfare

Email: ponezheva03@mail.ru
Moscow

V. V MALEEV

Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Welfare

Email: crie@pcr.ru
Moscow

References

  1. Ивашкин В.Т. (ред.) Болезни печени и желчевыводящих путей. Руководство для врачей. 2-е изд. М.: М-Вести, 2005; 115-151.
  2. Малеев В.В., Ситников И.Г., Бохонов М.С. Актуальные вопросы современной гепатологии. Москва-Ярославль, 2014. 510 с.
  3. Ющук Н.Д., Климова Е.А., Знойко О.О. Вирусные гепатиты. Клиника, диагностика, лечение. М.: ГЭОТАР-Медиа, 2012; 6-8.
  4. Маевская М.В. Алкогольная болезнь печени. Consilium medicum 2001; 3(6): 256-260.
  5. Naveau S., Gaude G., Asnacion A., Agostini H., Abella A., Barri-Ova N., Dauvois B., Prévot S., Ngo Y., Munteanu M., Balian A., Njiké-Nakseu M., Perlemuter G., Poynard T. Diagnostic and prognostic values of noninvastive biomarkers of fibrosis in patients with alcoholic liver disease. Hepatology 2009; 49(1): 97-105.
  6. Ивашкин В.Т., Павлов Ч.С. Фиброз печени. М.: ГЭОТАР-Медиа, 2011. 168 с.
  7. Chen C.-J., Yang H.-I., Su J., Jen C.L., You S.L., Lu S.N., Huang G.T., Iloeje U.H.; REVEAL-HBV Study Group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 2006; 295(1): 65-73.
  8. Iredale J.P. Models of liver fibrosis: exploring the dynamic nature of inflammation and repair in a solid organ. J. Clin. Invest. 2007; 117(3): 539-48.
  9. Wynn T.A. Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases. J. Chin. Invest. 2007; 117(3): 524-529.
  10. Сторожаков Г.И., Ивкова А.Н. Патогенетические аспекты фиброгенеза при хронических заболеваниях печени. Клинические перспективы гастроэнтерологии, гепатологии 2009; 2: 3-10.
  11. Ивкова А.Н., Федоров И.Г., Строжаков Г.И. Роль цитокинов в развитии фиброза печени. Клинические перспективы гастроэнтерологии, гепатологии. 2006; 1: 2-9.
  12. Сурков А.Н. Сывороточные маркеры фиброзирования при хронических заболеваниях печени у детей. Автореф. дис.. канд. мед. наук. М., 2009.
  13. Friedman S. Mechanisms of disease: mechanisms of hepatic fibrosis and therapeutic implications. Nat. Clin. Prac. Gastroenterol. Hepatol. 2004; 1: 98-105.
  14. Baroni G.S., D’Ambrosio L., Curto P., Casini A., Mancini R., Jezequel A.M., Benedetti A. Interferon gamma decreases hepatic stellate cell activation and extracellular matrix deposition in rat liver fibrosis. Hepatology 1996; 23: 1189- 1199.
  15. Walsh K.M., Timms P., Campbell S., MacSween R.N, Morris A.J. Plasma levels of matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of metalloproteinases-1 and -2 (TIMP-1 and TIMP-2) as noninvasive markers of liver disease in chronic hepatitis C: comparison using ROC analysis. Dig. Dis. Sci. 1999; 44(3): 624-630.
  16. Gressner A., Weiskirchen R. Modern pathogenetic concept of liver fibrosis suggest stellate cells and TGB-ß as major players and therapy targets. J. Cell. Mol. Med. 2006; 10(1): 46-99.
  17. Gressner O.A., Lahme B., Demirci I., Gressner A.M., Weiskirchen R. Differential effects of TGF-beta on connective tissue growth factor (CTGF/CCN2) expression in hepatic stellate cells and hepatocytes. J. Hepatol. 2007; 47(5): 699-710.
  18. Giannini E., Caglieris S., Ceppa P., Risso D., Lantieri P.B., Testa R. Serum pro-collagen III peptide levels are related to lobular necrosis in untreated patients with chronic hepatitis C. Eur. J. Gastroenterol. Hepatol. 2001; 13(2): 137-141.
  19. Regev A., Berho M., Jeffers L., Milikowski C., Molina E.G., Pyrsopoulos N.T., Feng Z.Z., Reddy K.R., Schiff E.R. Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection. Am. J. Gastroenterol. 2002; 97: 2614-2618.
  20. Винницкая Е.В. Диагностическая значимость сывороточных маркеров фиброза при хронических болезнях печени. Тер. архив 2013; 85(2): 27-31.
  21. Щекотова А.П. Эндотелин-1 - эффективный тест дифференциальной диагностики хронического гепатита и цирроза печени. Пермский медицинский журнал 2012; 29; 55-59.
  22. Bosch J., Berzigotti A., Garcia-Pagan J.C., Abraldes J.G. The management of portal hypertension: Rational basis, available treatment and future options. J. Hepatol. 2008; 48: 68-93.
  23. Leeming D.J., Karsdal M., Byrjalsen A., Bendtsen F., Trebicka J., Nielsen M.J., Christiansen C., Møller S., Krag A. Novel serological neo-epitope markers of extracellular matrix proteins for the detection of portal hypertension. Aliment Pharmacol. Ther. 2013; 38(9): 1086-1096.
  24. Ющук Н.Д., Знойко О.О. Сафиуллина Н.Х., Келли Е.И. Пункционная биопсия печени и возможности неинвазивного мониторинга фиброза при хроническом вирусном гепатите С. Клинические перспективы гастроэнтерологии, гепатологии 2002; 1: 9-16.
  25. Murawaki Y.,Ikuta Y., Okamoto K., Koda M., Kawasaki H. Diagnostic value of serum markers of connective tissue turnover for predicting histological staging and grading in patients with chronic hepatitis C. J. Gastroenterol. 2001; 36(6): 399-406.
  26. Bedossa P., Dargere D., Paradis V. Sampling variability of liver biopsy in chronic hepatitis C. Hepatology 2003; 38: 1449-1457.
  27. George S., Bacon B., Brunt E., Mihindukulasuriya K.L., Hoffmann J., Di Bisceglie A.M. Clinical, virologic, histologic, and biochemical outcomes after successful HCV therapy: A 5-year follow-up of 150 Patients. Hepatology 2009; 49: 729-738.
  28. Павлов Ч.С., Глушенков Д.В., Ивашкин В.Т. Современные возможности эластометрии, фибро- и акти-теста в диагностике фиброза печени. Рос. журн. гастроэнтерол., гепатол., колопроктол. 2008; 4: 43-52.
  29. Ogawa E., Furusyo N., Toyoda K., Takeoka H., Maeda S., Hayashi J. The longitudinal quantitative assessment by transient elastography of chronic hepatitis C patients treated with with pegylated interferon alpha-2d and ribavirin. Antiviral Res. 2009; 83(2): 127-134.
  30. Павлов Ч.С. Способ оценки степени фиброза печени при хроническом вирусном гепатите. Патент РФ № 2352950, 2009.
  31. Castera L., Foucher J., Bernard P. et al. Transient elastography (FibroScan) and FibroTest to assess liver fibrosis in inactive hepatitis: a perspective controlled study. Hepalogy 2006; 43(2): 373-274.
  32. Boeker K.H., Haberkorn C.I., Michels D., Flemming P., Manns M.P., Lichtinghagen R. Diagnostic potential of circulating TIMP-1 and MMP-2 as markers of liver fibrosis in patients with chronic hepatitis C. Clin. Chim. Acta 2002; 316(1-2): 71-81.
  33. Leroy V., Monier F., Bottari S., Trocme C., Sturm N., Hilleret M.N., Morel F., Zarski J.P. Circulating matrix metalloproteinases 1, 2, 9 and their inhibitors TIMP-1 and TIMP-2 as serum markers of liver fibrosis in patients with chronic hepatitis C: comparison with PIIINP and hyaluronic acid. Am. J. Gastroenterol. 2004; 99: 271-279.
  34. Nojgaard C., Johansen J.S., Christensen E., Skovgaard L.T., Price P.A., Becker U. Serum levels of YKL-40 and PIIINP as prognostic markers in patients with alcoholic liver disease. J. Hepatol. 2003; 39(2): 179-186.
  35. Gabrielli G.B., Capra F., Casaril M., Squarzoni S., Tognella P., Dagradi R., De Maria E., Colombari R., Corrocher R., De Sandre G. Serum laminin and type III procollagen in chronic hepatitis C. Diagnostic value in the assessment of disease activity and fibrosis. Clin. Chim. Acta 1997; 265(1): 21-31.
  36. Montalto G., Soresi M., Aragona F., Tripi S., Carroccio A., Anastasi G. Procollagen III and laminin in chronic viral hepatopathies. Presse Med. 1996; 25(2): 59-62.
  37. Hirayama C., Suzuki H., Takada A., Fujisawa K., Tanikawa K., Igarashi S. Serum type IV collagen in various liver diseases in comparison with serum 7S collagen, laminin, and type III procollagen peptide. J. Gastroenterol. 1996; 31(2): 242-248.
  38. Johansen J.S. Studies on serum YKL-40 as a biomarker in diseases with inflammation, tissue remodelling, fibroses and cancer. Dan. Med. Bull. 2006; 53(2): 172-209.
  39. Tianhui L., Xiaoming Wang, M.A. Karsdal M.A., Leeming D.J. Molecular Serum Markers of Liver Fibrosis. Presse Med. 2012; 7: 105-117.
  40. Wang T., Wang B., Liu X. Correlation of serum markers with fibrosis staging in chronic viral hepatitis. Zhonghua Bing Li Xue Za Zhi 1998; 27(3): 185-190.
  41. Savisens A., Serra I., Tural C., Tor J., Ojanguren I., Barluenga E., Rey-Joly C., Clotet B., Muga R. Hyaluronic acid, transforming growth factor ß1 and hepatic fibrosis in patients with chronic hepatitis C virus and human immunodeficiency virus co-infection. J. Viral. Hepat. 2009; 16(7): 513-518.
  42. Saitou Y., Shiraki K., Yamanaka Y., Yamaguchi Y., Kawakita T., Yamamoto N., Sugimoto K., Murata K., Nakano T. Noninvasive estimation of liver fibrosis and response to interferon therapy by a serum fibrogenesis marker, YKL- 40, in patients with HCV-associated liver disease. World J. Gastroenterol. 2005; 11(4): 476-481.
  43. Бондарева К.С. Совершенствование диагностики хронического гепатита и цирроза печени с учетом определения антител класса G к ламинину-1. Автореф. дис.. канд. мед. наук. Ростов-на-Дону, 2013.
  44. Kanzler S., Baumann M., Schirmacher P., Dries V., Bayer E., Gerken G., Dienes H.P., Lohse A.W. Prediction of progressive liver fibrosis in hepatitis C infection by serum and tissue levels of transforming growth factor-beta. J. Viral. Hepat. 2001; 8(6): 430-437.
  45. Flisiak R., Maxwell P., Prokopowicz D., Timms P.M., Panasiuk A. Plasma tissue inhibitor of metalloproteinases-1 and transforming growth factor beta 1-possible noninvasive biomarkers of hepatic fibrosis in patients with chronic B and C hepatitis. Hepatogastroenterology 2002; 49(47): 69-72.
  46. Kovalenko E., Tacke F., Gressner O.A., Zimmermann H.W., Lahme B., Janetzko A., Wiederholt T., Berg T., Müller T., Trautwein C., Gressner A.M., Weiskirchen R. Validation of connective tissue growth factor (CTGF/CCN2) and its gene polymorphisms as noninvasive biomarkers for the assessment of liver fibrosis. J. Viral. Hepat. 2009; 16(9): 612-620.
  47. Nakamura T., Sakata R., Sata M., Ueno T. Inhibition of transforming growth factor ß prevents progression of liver fibrosis and enhances hepatocyte regeneration in dimethylnitrosamine-treated rats. Hepatogy 2000; 32: 47-55.
  48. Zhang Y.X., Wu W.J., Zhang Y.Z., Feng Y.L., Zhou X.X., Pan Q. Noninvasive assessment of liver fibrosis with combined serum aminotransferase/platelet ratio index and hyaluronic acid in patients with chronic hepatitis B. World J. Gastroenterol. 2008; 14(46): 17-21.
  49. El-Gindy I., EL-Rahman A.T., El-Alim M.A., Zaki S. Diagnostic potential of serum matrix metalloproteinase- 2 and tissue inhibitor of metalloproteinase-1 as non-invasive markers of hepatic fibrosis in patients with HCV related chronic liver disease. Egypt. J. Immonol. 2003; 10(1): 27-35.
  50. Reif S., Somech R., Brazovski E., Reich R., Reich R., Reich R., Belson A., Konikoff F.M., Kessler A. Matrix metalloproteinases 2 and 9 are markers of inflammation but not of the degree of fibrosis in chronic hepatitis C. Digestion 2005; 71(2): 124-130.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies