While the introduction of the ELF test represents a major advance in the diagnostic armoury available for the clinical screening and management of CLD, further challenges remain. The ELF markers have been developed for a range of CLD. In specific diseases, other combinations of markers may perform better. So far, the development of algorithms such as ELF has relied on the testing of candidate markers. New discovery approaches such as metabonomics, proteomics and transcriptomics that make no assumptions about the relevance of specific molecules to disease processes may uncover new markers that complement or enhance the existing panels. Imaging of the liver using a variety of modalities, including ultrasound, elastography and magnetic resonance imaging, has advanced in parallel with minimally-invasive marker testing.30,31 The integration of these complementary modalities should further increase the diagnostic power available to clinicians. Determining the optimal combinations and suitability for specific CLD will be challenging.
The discovery of the ELF markers represents the dawn of a new era of early detection of treatable liver disease and the effective monitoring of CLD to evaluate the impact of interventions and the course of disease.
Disadvantages of Liver Biopsy
• Morbidity & mortality
• Sampling error
• Ordinal categorical variable to assess continuous biological process
• Costly & time consuming: requires hospital visit and expert
• Inter-observer variability: kappa scores 0.4-0.6
• Error rate: up to 25-35% of ≥1 stage
• Less experienced pathologists perform less well than “expert”
• Cannot perform repeat biopsy at short intervals to assess liver disease or effects of therapeutics due to the hazards
What is liver fibrosis?
Minimally-Invasive markers of liver fibrosis
Part of the article “Biomarkers of liver disease: the enhanced liver fibrosis test”
As published in CLI October 2007
William Rosenberg MD, D.Phil
Professor of Hepatology,
The Liver Group,
University of Southampton,
Julie Parkes MD
Public Health Science & Medical Statistics,
University of Southampton,
14. Rosenberg WM, Voelker M, Thiel R, Becka M, Burt A, Schuppan D et al. Serum markers detect the presence of liver fibrosis: a cohort study. Gastroenterology 2004; 127(6):1704-1713.
15. Parkes J, Bialek SR,Bell BP ,Terrault N, Zaman A, Sofair A, Guha IN, Cross R, Harris S, Roderick PJ, Rosenberg WMC. European Liver fibrosis markers accurately distinguish fibrosis severity in a cohort of patients with Chronic Hepatitis C; an external validation study. Hepatology 44[Suppl 1]. 2006.
16. Parkes J, Cross R, Harris S, Ryder S, Irving W, Zaitoun A. The Trent Hepatitis C Research Group, Rosenberg WMC. European liver fibrosis markers accurately distinguish fibrosis severity in Chronic Hepatitis C. Journal of Hepatology. 40 [Suppl 1]. 2005.
17. Guha IN, Aithal GP, Parkes J, Roderick PJ, Harris S, Cross R, Kaye P, Ryder SD, Rosenberg, WM. European liver fibrosis markers in Non Alcoholic Fatty Liver Disease (NAFLD); an external validation study. Hepatology 44 Suppl 1. 2006.
18. Parks J, Mayo M, Cross R, Harris S, Roderick PJ, Coombs B, Huet B. The PUMPS Investigators and W.M. Rosenberg . European liver fibrosis markers accurately distinguish fibrosis severity in primary biliary cirrhosis; an external validation study. Hepatology 44 Suppl 1. 2006.
19. Non-invasive markers of fibrosis in non-alcoholic fatty liver disease: validating the European Liver Fibrosis panel and exploring simple markers. Hepatology 2007 (in press).
20. Mayo M., Parkes J, Huet B, Combes B, Mills S, Markin R, et al. Serum fibrosis markers predict future clinical decompensation in primary biliary cirrhosis bettter than liver biopsy, bilirubin, or Mayo risk score. Hepatology 44 Suppl 1. 2006.
21. Guha IN, Parkes J, Roderick PR, Harris S, Rosenberg WM. Non-invasive markers associated with liver fibrosis in non-alcoholic fatty liver disease 2. GUT 2006; 55(11):1650-1660.
22. Parkes J, Guha IN, Roderick P, Rosenberg W. Performance of serum marker panels for liver fibrosis in chronic hepatitis C. Journal of Hepatology 2006; 44:462-474.
23. 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(9262):1069-1075.
24. Ratziu V, Massard J, Charlotte F, Messous D, Imbert-Bismut F, Bonyhay L et al. Diagnostic value of biochemical markers (Fibro Test-FibroSURE) for the prediction of liver fibrosis in patients with non-alcholic fatty liver disease. BMC Gastroenterology 2006; 6(6):1-13.
25. Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C.. Hepatology 2003; 38(2):518-526.
26. Forns X, Ampurdanes S, Llovet JM, Aponte J, Quinto L, Martinez-Bauer E et al. Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model.. Hepatology 2002; 36(4 Pt 1):986-992.
27. Patel K, Muir AJ, McHutchison JG. Validation of a simple predictive model for the identification of mild hepatic fibrosis in chronic hepatitis C patients.. Hepatology 2003; 37(5):1222-1223.
28. Hepascore: An accurate validated predictor of liver fibrosis in chronic hepatitis C infection. Clinical Chemistry 51 (10) 1-7.
29. Cales P, Oberti F, Michalak S, Hubert-Fouchard I, Rousselet MC, Konate A et al. A novel panel of blood markers to assess the degree of liver fibrosis 10. Hepatology 2005; 42(6):1373-1381.
30. Ganne-Carríe N, Ziol M, Ledinghen V, Douvin C, Marcellin P, Castera L et al. Accuracy of liver stiffness measurement for the diagnosis of cirrhosis in patients with chronic liver disease. Hepatology 2006; 44:1511-1517.
31. Foucher J,Chanteloup E, Vergniol J, Castera L,Le Bail B, Adhoute X, Bertet J, Couzigou P, de Ledinghen V. Diagnosis of cirrhosis by transient elastography (FibroScan): a prospective study. GUT 2006; 55(3):403-408.
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