Skip to main content
SpringerLink
Log in
Book cover

Diagnostic Methods for Cirrhosis and Portal Hypertension pp 63–82Cite as

Non-invasive Serum Markers of Fibrosis

  • Chapter
  • First Online:

Abstract

Liver fibrosis occurs when a chronic injury of any etiology leads to excessive accumulation of extracellular matrix proteins in the hepatic parenchyma. Staging of liver fibrosis and subsequent identification of patients with liver cirrhosis and portal hypertension is pivotal for the management and prognostication of chronic liver diseases of any etiology. Liver biopsy and the measurement of hepatic venous pressure gradient through transjugular catheterization of hepatic vein have long been the gold standard of reference to diagnose hepatic cirrhosis and for detection of clinically significant portal hypertension, respectively. However, due to their cost and invasiveness, recent years have seen the development and implementation of non-invasive serum biomarkers. Some serum fibrosis biomarkers present with high accuracy for diagnosis of liver cirrhosis and monitoring of its related complications. Moreover, they demonstrate prognostic value to predict clinical outcomes deriving from portal hypertension complications. Serum fibrosis biomarkers have been gradually incorporated into clinical guidelines and are progressively becoming first-line diagnostic tests for liver cirrhosis, with significant reduction in the need for liver biopsy. We here provide an update on pathophysiological rationale on the diagnostic and prognostic application of serum fibrosis biomarkers and on their accuracy in clinical scenarios related to liver cirrhosis and its complications.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   69.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   89.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   119.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Roulot D, Costes JL, Buyck JF, et al. Transient elastography as a screening tool for liver fibrosis and cirrhosis in a community-based population aged over 45 years. Gut. 2011;60:977–84.

    Article  CAS  PubMed  Google Scholar 

  2. Friedman SL. Mechanisms of hepatic fibrogenesis. Gastroenterology. 2008;134:1655–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Neff GW, Duncan CW, Schiff ER. The current economic burden of cirrhosis. Gastroenterol Hepatol (N Y). 2011;7:661–71.

    Google Scholar 

  4. Garcia-Tsao G, Friedman S, Iredale J, Pinzani M. Now there are many (stages) where before there was one: in search of a pathophysiological classification of cirrhosis. Hepatology. 2010;51:1445–9.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Dulai PS, Singh S, Patel J, et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: systematic review and meta-analysis. Hepatology. 2017;65:1557–65.

    Article  CAS  PubMed  Google Scholar 

  6. D’Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol. 2006;44:217–31.

    Article  PubMed  Google Scholar 

  7. Durand F, Valla D. Assessment of prognosis of cirrhosis. Semin Liver Dis. 2008;28:110–22.

    Article  CAS  PubMed  Google Scholar 

  8. Rockey DC, Caldwell SH, Goodman ZD, Nelson RC, Smith AD, American Association for the Study of Liver D. Liver biopsy. Hepatology. 2009;49:1017–44.

    Article  PubMed  Google Scholar 

  9. de Franchis R, Baveno VIF. Expanding consensus in portal hypertension: report of the Baveno VI consensus workshop: stratifying risk and individualizing care for portal hypertension. J Hepatol. 2015;63:743–52.

    Article  PubMed  Google Scholar 

  10. Lee UE, Friedman SL. Mechanisms of hepatic fibrogenesis. Best Pract Res Clin Gastroenterol. 2011;25:195–206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bataller R, Brenner DA. Liver fibrosis. J Clin Invest. 2005;115:209–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ishak K, Baptista A, Bianchi L, et al. Histological grading and staging of chronic hepatitis. J Hepatol. 1995;22:696–9.

    Article  CAS  PubMed  Google Scholar 

  13. Bataller R, North KE, Brenner DA. Genetic polymorphisms and the progression of liver fibrosis: a critical appraisal. Hepatology. 2003;37:493–503.

    Article  CAS  PubMed  Google Scholar 

  14. Anstee QM, Wright M, Goldin R, Thursz MR. Parenchymal extinction: coagulation and hepatic fibrogenesis. Clin Liver Dis. 2009;13:117–26.

    Article  PubMed  Google Scholar 

  15. Tsuchida T, Friedman SL. Mechanisms of hepatic stellate cell activation. Nat Rev Gastroenterol Hepatol. 2017;14:397–411.

    Article  CAS  PubMed  Google Scholar 

  16. Failli P, Ruocco C, De Franco R, et al. The mitogenic effect of platelet-derived growth factor in human hepatic stellate cells requires calcium influx. Am J Phys. 1995;269:C1133–9.

    Article  CAS  Google Scholar 

  17. Kluwe J, Pradere JP, Gwak GY, et al. Modulation of hepatic fibrosis by c-Jun-N-terminal kinase inhibition. Gastroenterology. 2010;138:347–59.

    Article  CAS  PubMed  Google Scholar 

  18. Gressner AM. Transdifferentiation of hepatic stellate cells (Ito cells) to myofibroblasts: a key event in hepatic fibrogenesis. Kidney Int Suppl. 1996;54:S39–45.

    CAS  PubMed  Google Scholar 

  19. Meyer DH, Bachem MG, Gressner AM. Modulation of hepatic lipocyte proteoglycan synthesis and proliferation by Kupffer cell-derived transforming growth factors type beta 1 and type alpha. Biochem Biophys Res Commun. 1990;171:1122–9.

    Article  CAS  PubMed  Google Scholar 

  20. Win KM, Charlotte F, Mallat A, et al. Mitogenic effect of transforming growth factor-beta 1 on human Ito cells in culture: evidence for mediation by endogenous platelet-derived growth factor. Hepatology. 1993;18:137–45.

    Article  CAS  PubMed  Google Scholar 

  21. Yoshiji H, Kuriyama S, Yoshii J, et al. Vascular endothelial growth factor and receptor interaction is a prerequisite for murine hepatic fibrogenesis. Gut. 2003;52:1347–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Kinoshita K, Iimuro Y, Fujimoto J, et al. Targeted and regulable expression of transgenes in hepatic stellate cells and myofibroblasts in culture and in vivo using an adenoviral Cre/loxP system to antagonise hepatic fibrosis. Gut. 2007;56:396–404.

    Article  CAS  PubMed  Google Scholar 

  23. Breitkopf K, Godoy P, Ciuclan L, Singer MV, Dooley S. TGF-beta/Smad signaling in the injured liver. Z Gastroenterol. 2006;44:57–66.

    Article  CAS  PubMed  Google Scholar 

  24. Saxena NK, Ikeda K, Rockey DC, Friedman SL, Anania FA. Leptin in hepatic fibrosis: evidence for increased collagen production in stellate cells and lean littermates of ob/ob mice. Hepatology. 2002;35:762–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wang J, Leclercq I, Brymora JM, et al. Kupffer cells mediate leptin-induced liver fibrosis. Gastroenterology. 2009;137:713–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Seki E, Schwabe RF. Hepatic inflammation and fibrosis: functional links and key pathways. Hepatology. 2015;61:1066–79.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Peck-Radosavljevic M. Thrombocytopenia in chronic liver disease. Liver Int. 2016;37:778–93.

    Article  PubMed  Google Scholar 

  28. Qian S, Fu F, Li W, Chen Q, de Sauvage FJ. Primary role of the liver in thrombopoietin production shown by tissue-specific knockout. Blood. 1998;92:2189–91.

    CAS  PubMed  Google Scholar 

  29. Saitou Y, Shiraki K, Yamanaka Y, et al. 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;11:476–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Sebastiani G, Gkouvatsos K, Plebani M. Non-invasive assessment of liver fibrosis: it is time for laboratory medicine. Clin Chem Lab Med. 2011;49:13–32.

    Article  CAS  PubMed  Google Scholar 

  31. Boeker KH, Haberkorn CI, Michels D, Flemming P, Manns MP, 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;316:71–81.

    Article  CAS  PubMed  Google Scholar 

  32. Cales P, Oberti F, Michalak S, et al. A novel panel of blood markers to assess the degree of liver fibrosis. Hepatology. 2005;42:1373–81.

    Article  PubMed  Google Scholar 

  33. Leroy V, Hilleret MN, Sturm N, et al. Prospective comparison of six non-invasive scores for the diagnosis of liver fibrosis in chronic hepatitis C. J Hepatol. 2007;46:775–82.

    Article  PubMed  Google Scholar 

  34. Leroy V, Sturm N, Faure P, et al. Prospective evaluation of FibroTest(R), FibroMeter(R), and HepaScore(R) for staging liver fibrosis in chronic hepatitis B: comparison with hepatitis C. J Hepatol. 2014;61:28–34.

    Article  PubMed  Google Scholar 

  35. Adams LA, Bulsara M, Rossi E, et al. Hepascore: an accurate validated predictor of liver fibrosis in chronic hepatitis C infection. Clin Chem. 2005;51:1867–73.

    Article  CAS  PubMed  Google Scholar 

  36. Becker L, Salameh W, Sferruzza A, et al. Validation of hepascore, compared with simple indices of fibrosis, in patients with chronic hepatitis C virus infection in United States. Clin Gastroenterol Hepatol. 2009;7:696–701.

    Article  PubMed  Google Scholar 

  37. Huang Y, Adams LA, Joseph J, Bulsara MK, Jeffrey GP. The ability of Hepascore to predict liver fibrosis in chronic liver disease: a meta-analysis. Liver Int. 2017;37:121–31.

    Article  PubMed  Google Scholar 

  38. Rosenberg WM, Voelker M, Thiel R, et al. Serum markers detect the presence of liver fibrosis: a cohort study. Gastroenterology. 2004;127:1704–13.

    Article  PubMed  Google Scholar 

  39. Imbert-Bismut F, Ratziu V, Pieroni L, Charlotte F, Benhamou Y, Poynard T. Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study. Lancet. 2001;357:1069–75.

    Article  CAS  PubMed  Google Scholar 

  40. Sebastiani G, Vario A, Guido M, et al. Stepwise combination algorithms of non-invasive markers to diagnose significant fibrosis in chronic hepatitis C. J Hepatol. 2006;44:686–93.

    Article  CAS  PubMed  Google Scholar 

  41. Shaheen AA, Wan AF, Myers RP. FibroTest and FibroScan for the prediction of hepatitis C-related fibrosis: a systematic review of diagnostic test accuracy. Am J Gastroenterol. 2007;102:2589–600.

    Article  PubMed  Google Scholar 

  42. McGary CT, Raja RH, Weigel PH. Endocytosis of hyaluronic acid by rat liver endothelial cells. Evidence for receptor recycling. Biochem J. 1989;257:875–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Guechot J, Laudat A, Loria A, Serfaty L, Poupon R, Giboudeau J. Diagnostic accuracy of hyaluronan and type III procollagen amino-terminal peptide serum assays as markers of liver fibrosis in chronic viral hepatitis C evaluated by ROC curve analysis. Clin Chem. 1996;42:558–63.

    CAS  PubMed  Google Scholar 

  44. Montalto G, Soresi M, Aragona F, et al. Procollagen III and laminin in chronic viral hepatopathies. Presse Med. 1996;25:59–62.

    CAS  PubMed  Google Scholar 

  45. Misaki M, Shima T, Yano Y, et al. Basement membrane-related and type III procollagen-related antigens in serum of patients with chronic viral liver disease. Clin Chem. 1990;36:522–4.

    CAS  PubMed  Google Scholar 

  46. Walsh KM, Timms P, Campbell S, MacSween RN, Morris AJ. 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;44:624–30.

    Article  CAS  PubMed  Google Scholar 

  47. Sebastiani G, Alberti A. Non invasive fibrosis biomarkers reduce but not substitute the need for liver biopsy. World J Gastroenterol. 2006;12:3682–94.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Dusheiko G. Side effects of alpha interferon in chronic hepatitis C. Hepatology. 1997;26:112S–21S.

    Article  CAS  PubMed  Google Scholar 

  49. Pradat P, Alberti A, Poynard T, et al. Predictive value of ALT levels for histologic findings in chronic hepatitis C: a European collaborative study. Hepatology. 2002;36:973–7.

    Article  PubMed  Google Scholar 

  50. Giannini E, Risso D, Botta F, et al. Validity and clinical utility of the aspartate aminotransferase-alanine aminotransferase ratio in assessing disease severity and prognosis in patients with hepatitis C virus-related chronic liver disease. Arch Intern Med. 2003;163:218–24.

    Article  PubMed  Google Scholar 

  51. McPherson S, Stewart SF, Henderson E, Burt AD, Day CP. Simple non-invasive fibrosis scoring systems can reliably exclude advanced fibrosis in patients with non-alcoholic fatty liver disease. Gut. 2010;59:1265–9.

    Article  PubMed  Google Scholar 

  52. Harrison SA, Oliver D, Arnold HL, Gogia S, Neuschwander-Tetri BA. Development and validation of a simple NAFLD clinical scoring system for identifying patients without advanced disease. Gut. 2008;57:1441–7.

    Article  CAS  PubMed  Google Scholar 

  53. Lin ZH, Xin YN, Dong QJ, et al. Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis. Hepatology. 2011;53:726–36.

    Article  PubMed  Google Scholar 

  54. Shah AG, Lydecker A, Murray K, et al. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2009;7:1104–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Lieber CS, Weiss DG, Morgan TR, Paronetto F. Aspartate aminotransferase to platelet ratio index in patients with alcoholic liver fibrosis. Am J Gastroenterol. 2006;101:1500–8.

    Article  CAS  PubMed  Google Scholar 

  56. Fujii H, Enomoto M, Fukushima W, et al. Noninvasive laboratory tests proposed for predicting cirrhosis in patients with chronic hepatitis C are also useful in patients with non-alcoholic steatohepatitis. J Gastroenterol. 2009;44:608–14.

    Article  PubMed  Google Scholar 

  57. Shin WG, Park SH, Jang MK, et al. Aspartate aminotransferase to platelet ratio index (APRI) can predict liver fibrosis in chronic hepatitis B. Dig Liver Dis. 2008;40:267–74.

    Article  CAS  PubMed  Google Scholar 

  58. Lok AS, Ghany MG, Goodman ZD, et al. Predicting cirrhosis in patients with hepatitis C based on standard laboratory tests: results of the HALT-C cohort. Hepatology. 2005;42:282–92.

    Article  PubMed  Google Scholar 

  59. Koda M, Matunaga Y, Kawakami M, Kishimoto Y, Suou T, Murawaki Y. FibroIndex, a practical index for predicting significant fibrosis in patients with chronic hepatitis C. Hepatology. 2007;45:297–306.

    Article  PubMed  Google Scholar 

  60. Forns X, Ampurdanes S, Llovet JM, et al. Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model. Hepatology. 2002;36:986–92.

    Article  PubMed  Google Scholar 

  61. Zhou K, Gao CF, Zhao YP, et al. Simpler score of routine laboratory tests predicts liver fibrosis in patients with chronic hepatitis B. J Gastroenterol Hepatol. 2010;25:1569–77.

    Article  PubMed  Google Scholar 

  62. Naveau S, Gaude G, Asnacios A, et al. Diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with alcoholic liver disease. Hepatology. 2009;49:97–105.

    Article  PubMed  Google Scholar 

  63. Sterling RK, Lissen E, Clumeck N, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43:1317–25.

    Article  CAS  PubMed  Google Scholar 

  64. Vallet-Pichard A, Mallet V, Nalpas B, et al. FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. Comparison with liver biopsy and fibrotest. Hepatology. 2007;46:32–6.

    Article  CAS  PubMed  Google Scholar 

  65. Mallet V, Dhalluin-Venier V, Roussin C, et al. The accuracy of the FIB-4 index for the diagnosis of mild fibrosis in chronic hepatitis B. Aliment Pharmacol Ther. 2009;29:409–15.

    Article  CAS  PubMed  Google Scholar 

  66. Hsieh YY, Tung SY, Lee IL, et al. FibroQ: an easy and useful noninvasive test for predicting liver fibrosis in patients with chronic viral hepatitis. Chang Gung Med J. 2009;32:614–22.

    PubMed  Google Scholar 

  67. Hsieh YY, Tung SY, Lee K, et al. Routine blood tests to predict liver fibrosis in chronic hepatitis C. World J Gastroenterol. 2012;18:746–53.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Angulo P, Hui JM, Marchesini G, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007;45:846–54.

    Article  CAS  PubMed  Google Scholar 

  69. Wai CT, Greenson JK, Fontana RJ, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003;38:518–26.

    Article  PubMed  Google Scholar 

  70. Toniutto P, Fabris C, Bitetto D, et al. Role of AST to platelet ratio index in the detection of liver fibrosis in patients with recurrent hepatitis C after liver transplantation. J Gastroenterol Hepatol. 2007;22:1904–8.

    Article  PubMed  Google Scholar 

  71. Loaeza-del-Castillo A, Paz-Pineda F, Oviedo-Cardenas E, Sanchez-Avila F, Vargas-Vorackova FAST. To platelet ratio index (APRI) for the noninvasive evaluation of liver fibrosis. Ann Hepatol. 2008;7:350–7.

    CAS  PubMed  Google Scholar 

  72. Halfon P, Penaranda G, Renou C, Bourliere M. External validation of FibroIndex. Hepatology. 2007;46:280–1. author reply 1–2

    Article  PubMed  Google Scholar 

  73. European Association for Study of L, Asociacion Latinoamericana para el Estudio del H. EASL-ALEH Clinical Practice Guidelines: non-invasive tests for evaluation of liver disease severity and prognosis. J Hepatol. 2015;63:237–64.

    Article  Google Scholar 

  74. Sebastiani G, Halfon P, Castera L, et al. SAFE biopsy: a validated method for large-scale staging of liver fibrosis in chronic hepatitis C. Hepatology. 2009;49:1821–7.

    Article  PubMed  Google Scholar 

  75. Sebastiani G, Vario A, Guido M, Alberti A. Sequential algorithms combining non-invasive markers and biopsy for the assessment of liver fibrosis in chronic hepatitis B. World J Gastroenterol. 2007;13:525–31.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Bourliere M, Penaranda G, Renou C, et al. Validation and comparison of indexes for fibrosis and cirrhosis prediction in chronic hepatitis C patients: proposal for a pragmatic approach classification without liver biopsies. J Viral Hepat. 2006;13:659–70.

    Article  CAS  PubMed  Google Scholar 

  77. Boursier J, de Ledinghen V, Zarski JP, et al. Comparison of 8 diagnostic algorithms for liver fibrosis in hepatitis C: new algorithms are more precise and entirely non-invasive. Hepatology. 2012;55:58–67.

    Article  PubMed  Google Scholar 

  78. Bourliere M, Penaranda G, Ouzan D, et al. Optimized stepwise combination algorithms of non-invasive liver fibrosis scores including Hepascore in hepatitis C virus patients. Aliment Pharmacol Ther. 2008;28:458–67.

    Article  CAS  PubMed  Google Scholar 

  79. Sebastiani G, Halfon P, Castera L, et al. Comparison of three algorithms of non-invasive markers of fibrosis in chronic hepatitis C. Aliment Pharmacol Ther. 2012;35:92–104.

    Article  CAS  PubMed  Google Scholar 

  80. Boursier J, Cales P. Combination of fibrosis tests: sequential or synchronous? Hepatology. 2009;50:656–7. author reply 7

    Article  PubMed  Google Scholar 

  81. Castera L, Sebastiani G, Le Bail B, de Ledinghen V, Couzigou P, Alberti A. Prospective comparison of two algorithms combining non-invasive methods for staging liver fibrosis in chronic hepatitis C. J Hepatol. 2010;52:191–8.

    Article  PubMed  Google Scholar 

  82. Zaman A, Hapke R, Flora K, Rosen HR, Benner K. Factors predicting the presence of esophageal or gastric varices in patients with advanced liver disease. Am J Gastroenterol. 1999;94:3292–6.

    Article  CAS  PubMed  Google Scholar 

  83. Sebastiani G, Tempesta D, Fattovich G, et al. Prediction of oesophageal varices in hepatic cirrhosis by simple serum non-invasive markers: results of a multicenter, large-scale study. J Hepatol. 2010;53:630–8.

    Article  PubMed  Google Scholar 

  84. Berzigotti A, Gilabert R, Abraldes JG, et al. Noninvasive prediction of clinically significant portal hypertension and esophageal varices in patients with compensated liver cirrhosis. Am J Gastroenterol. 2008;103:1159–67.

    Article  CAS  PubMed  Google Scholar 

  85. Galal GM, Amin NF, Abdel Hafeez HA, El-Baz MA. Can serum fibrosis markers predict medium/large oesophageal varices in patients with liver cirrhosis? Arab J Gastroenterol. 2011;12:62–7.

    Article  PubMed  Google Scholar 

  86. Sandahl TD, McGrail R, Moller HJ, et al. The macrophage activation marker sCD163 combined with markers of the Enhanced Liver Fibrosis (ELF) score predicts clinically significant portal hypertension in patients with cirrhosis. Aliment Pharmacol Ther. 2016;43:1222–31.

    Article  CAS  PubMed  Google Scholar 

  87. Mamori S, Searashi Y, Matsushima M, et al. Serum type IV collagen level is predictive for esophageal varices in patients with severe alcoholic disease. World J Gastroenterol. 2008;14:2044–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Thabut D, Trabut JB, Massard J, et al. Non-invasive diagnosis of large oesophageal varices with FibroTest in patients with cirrhosis: a preliminary retrospective study. Liver Int. 2006;26:271–8.

    Article  PubMed  Google Scholar 

  89. Castera L, Le Bail B, Roudot-Thoraval F, et al. Early detection in routine clinical practice of cirrhosis and oesophageal varices in chronic hepatitis C: comparison of transient elastography (FibroScan) with standard laboratory tests and non-invasive scores. J Hepatol. 2009;50:59–68.

    Article  PubMed  Google Scholar 

  90. Yano M, Kumada H, Kage M, et al. The long-term pathological evolution of chronic hepatitis C. Hepatology. 1996;23:1334–40.

    Article  CAS  PubMed  Google Scholar 

  91. Ngo Y, Munteanu M, Messous D, et al. A prospective analysis of the prognostic value of biomarkers (FibroTest) in patients with chronic hepatitis C. Clin Chem. 2006;52:1887–96.

    Article  CAS  PubMed  Google Scholar 

  92. Nunes D, Fleming C, Offner G, et al. Noninvasive markers of liver fibrosis are highly predictive of liver-related death in a cohort of HCV-infected individuals with and without HIV infection. Am J Gastroenterol. 2010;105:1346–53.

    Article  PubMed  Google Scholar 

  93. Vergniol J, Foucher J, Terrebonne E, et al. Non-invasive tests for fibrosis and liver stiffness predict 5-year outcomes of patients with chronic hepatitis C. Gastroenterology. 2011;140:1970–9.

    Article  PubMed  Google Scholar 

  94. Poynard T, Vergniol J, Ngo Y, et al. Staging chronic hepatitis C in seven categories using fibrosis biomarker (FibroTest) and transient elastography (FibroScan). J Hepatol. 2014;61:994–1003.

    Article  PubMed  Google Scholar 

  95. Vergniol J, Boursier J, Coutzac C, et al. Evolution of noninvasive tests of liver fibrosis is associated with prognosis in patients with chronic hepatitis C. Hepatology. 2014;60:65–76.

    Article  PubMed  Google Scholar 

  96. Boursier J, Vergniol J, Guillet A, et al. Diagnostic accuracy and prognostic significance of blood fibrosis tests and liver stiffness measurement by FibroScan in non-alcoholic fatty liver disease. J Hepatol. 2016;65:570–8.

    Article  PubMed  Google Scholar 

  97. Singh S, Venkatesh SK, Loomba R, et al. Magnetic resonance elastography for staging liver fibrosis in non-alcoholic fatty liver disease: a diagnostic accuracy systematic review and individual participant data pooled analysis. Eur Radiol. 2016;26:1431–40.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Royal Victoria Hospital, McGill University Health Centre, Montreal, QC, Canada

    Thomas Pembroke & Giada Sebastiani

  2. School of Medicine, Cardiff University, Cardiff, UK

    Thomas Pembroke

Authors
  1. Thomas Pembroke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giada Sebastiani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giada Sebastiani .

Editor information

Editors and Affiliations

  1. Inselspital, University of Bern, UVCM, DMLL, Hepatology Inselspital, University of Bern, Berne, Switzerland

    Annalisa Berzigotti

  2. Hospital Clinic, Hepatic Hemodynamic Laboratory Hospital Clinic, Barcelona, Spain

    Jaime Bosch

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Pembroke, T., Sebastiani, G. (2018). Non-invasive Serum Markers of Fibrosis. In: Berzigotti, A., Bosch, J. (eds) Diagnostic Methods for Cirrhosis and Portal Hypertension. Springer, Cham. https://doi.org/10.1007/978-3-319-72628-1_5

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-72628-1_5

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-72627-4

  • Online ISBN: 978-3-319-72628-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation