US Gastroenterology & Hepatology Review, 2006;(2):51-54
Longer version of article from Reference Section:
The consensus conference statements recommend liver biopsy in the management of almost all patients with the most frequent chronic liver diseases: chronic hepatitis C (HCV) and B (HBV), non-alcoholic fatty liver disease (NAFLD), with its risk of non alcoholic steato-hepatitis (NASH), and alcoholic fatty liver disease (AFLD) with its risk of non alcoholic steatohepatitis (ASH),1–5 but also underline the necessity of developing reliable non-invasive tests.2,3 Numerous studies strongly suggest that due to the limitations and risks of biopsy,5–9 as well as the improvement of the diagnostic accuracy of biochemical markers,5,10–12 liver biopsy should no longer be considered mandatory.13
Diagnostic Values of Non-invasive Alternatives
Among the non-invasive alternatives to liver biopsy,5several studies have demonstrated the predictive value of two combinations of simple serum biochemical markers: FibroTest™ (or HCV-FibroSURE™ in the US) for the quantitative assessment of fibrosis and ActiTest™ (or HCV-FibroSURE in the US) for the quantitative assessment of necroinflammatory occurrences.10–12 Similar results have not been obtained with other diagnostic tests.10-18
Since September 2002 FibroSURE-FibroTest-ActiTests (FT-AT) have been used in several countries as an alternative to liver biopsy. Several systematic reviews5,10,15 and independent prospective studies19–23 have validated these panels of tests.
The diagnostic values of FT were similar for the four most frequent fibrotic liver diseases: HCV,10–12,14–15,19–30 HBV,21,31,32 NAFLD33 and AFLD19,21,34 (see Table 1 and Figure 1). The diagnostic values were similar between intermediate or extreme stages as assessed by area under the receiver operator characteristic (AUROC) between all stage combinations.10 It has been also demonstrated that biomarkers may provide a more accurate (quantitative and reproducible) picture of fibrogenic and necrotic events occurring within the liver than a low-quality liver biopsy. A prospective study observed that 18% of discordances were attributable to biopsy failure (mostly due to small length) and 2% to the failure of the tests.11 The prospective follow-up of these patients during five years has also demonstrated that the prognostic value of FibroSURE was greater than that of biopsy for predicting mortality and morbidity.12
Since June 2006 three new combinations of biomarkers have completed the spectrum of non-invasive liver biomarkers: SteatoTest™, for the diagnosis of steatosis (fatty liver),35 NashTest™ for the diagnosis of NASH, 36 and AshTest™ for the diagnosis of ASH.37 In the US, Nash-FibroSURE™ included FibroTest-SteatoTest and NashTest; Ash-FibroSURE™ included FibroTest- SteatoTest and AshTest.
References:
1. Bravo A A, Sheth S G and Chopra S,“Liver biopsy”, N Engl J Med (2001), 344; pp. 495–500.
2. Dienstag J, “The role of liver biopsy in chronic hepatitis C”, Hepatology (2002), 36; pp. S152–S160.
3. Gebo K A, Herlong H F,Torbenson M S, Jenckes M W, Chander G,“Role of liver biopsy in management of chronic hepatitis
C:A systematic review”, Hepatology (2002), 36: pp. S161–S172.
4. Afdhal N H, “Diagnosing fibrosis in hepatitis C: is the pendulum swinging from biopsy to blood tests?”, Hepatology
(2003), 37: pp. 972–974.
5. Sebastiani G, Alberti A, “Non invasive fibrosis biomarkers reduce but not substitute the need for liver biopsy”, World J
Gastroenterol. (2006); 12: pp. 3,682–3,694.
6. Regev A, Berho M, Jeffers L J, et al.,“Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV
infection”, Am J Gastroenterol (2002), 97: pp. 2,614–2,618.
7. Colloredo G, Guido M, Sonzogni A, Leandro G, “Impact of liver biopsy size on histological evaluation of chronic viral
hepatitis: the smaller the sample, the milder the disease”, J Hepatol (2003), 39: pp. 239–244.
8. Bedossa P, Dargère D, Paradis V, “Sampling variability of liver fibrosis in chronic hepatitis C”, Hepatology (2003), 38;
pp. 1,449–1,457.
9. Poynard T, Ratziu V, Bedossa P,“Appropriateness of liver biopsy”, Can J Gastroenterol (2000), 14: pp. 543–548.
10. Poynard T, Imbert-Bismut F, Munteanu M, et al.,“Overview of the diagnostic value of biochemical markers of liver fibrosis
(FibroTest, HCV-Fibrosure) and necrosis (ActiTest) in patients with chronic hepatitis C”, Comp Hepatol (2004), 3: p. 8.
11. Poynard T, Munteanu M, Imbert-Bismut F, et al.,“Prospective Analysis of Discordant Results between Biochemical Markers
and Biopsy in Patients with Chronic Hepatitis C”, Clin Chem (2004), 50: pp. 1,344–1,355.
12. 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(10): pp. 1887–1896. Epub 2006 Aug 24.
13. Poynard T, Ratziu V, Benhamou Y, et al., “Biomarkers as a first-line estimate of injury in chronic liver diseases: time for a
moratorium on liver biopsy?”, Gastroenterology. (2005); 128: pp. 1146–1148.
14. Imbert-Bismut F, Ratziu V, Laurence Pieroni L, et al.,“Biochemical markers of liver fibrosis in patients with hepatitis C virus
infection: a prospective study”, Lancet (2001), 357: pp. 1,069–1,075.
15. Poynard T, Imbert-Bismut F, Ratziu V, “Serum markers of liver fibrosis”, Hepatology Rev (2004), 1: pp. 25–33.
16. Myers R P, de Torres M, Imbert-Bismut F, et al., “Biochemical markers of fibrosis in patients with chronic hepatitis C: a
comparison with prothrombin time, platelet count and the age-platelet index”, Dig Dis Sci (2003), 48: pp. 146–153.
17. Thabut D, Simon M, Myers R P, et al., “Non-invasive prediction of fibrosis in patients with chronic hepatitis C”, (letter)
Hepatology (2003), 37: pp. 1,220–1,221.
18. Le Calvez S, Thabut D, Messous D, et al., “Fibrotest has higher Predictive values than APRI for Fibrosis Diagnosis in
Patients With Chronic Hepatitis C” (letter) Hepatology (2004), 39: pp. 862–863.
19. Callewaert N,Van Vlierberghe H,Van Hecke A, et al.,“Non-invasive diagnosis of liver cirrhosis using DNA sequencer-based
total serum protein glycomics”, Nature Med (2004), 10; pp. 1–6.
20. Castéra L,Vergniol J, Foucher J, et al.,“Prospective comparison of transient elastography, Fibrotest,APRI and liver biopsy for
the assessment of fibrosis in chronic hepatitis C”, Gastroenterology (2005); 128: pp. 343–350.
21. Cales P, Oberti F, Michalak S, et al., “A novel panel of blood markers to assess the degree of liver fibrosis”, Hepatology
(2005); 42: 1373–1381.
22. Halfon P, Bourliere M, Deydier R, et al., “Independent prospective multicenter validation of biochemical markers (Fibrotest-
Actitest) for the prediction of liver fibrosis and activity in patients with chronic hepatitis”, C Am J Gastro (2006); 101:
pp. 547–555.
23. 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: pp. 686–693.
24. Poynard T, Imbert-Bismut F, Ratziu V, et al.,“Biochemical markers of liver fibrosis in patients infected by Hepatitis C Virus:
Longitudinal validation in a randomized trial”, J.Viral Hepatitis (2002), 9: pp. 128–133.
25. Myers R P, Benhamou Y, Imbert-Bismut F, et al.,“Serum biochemical markers accurately predict liver fibrosis in HIV and
hepatitis C virus-coinfected patients”, AIDS (2003), 17: p. 1–5.
26. Rossi E,Adams L, Prins A, et al.,“Validation of the FibroTest biochemical markers score in assessing liver fibrosis in hepatitis
C patients”, Clin Chem (2003), 49: pp. 450–454.
27. Poynard T, Imbert-Bismut F, Ratziu V, et al.,“Fibrotest even better than liver biopsy?”, Clin Chem (21 March 2003),
electronic letter available at: http://www.clinchem.org/cgi/eletters/49/3/450
28. Varaut A, Fontaine H, Serpaggi J, et al., “Diagnostic accuracy of the fibrotest in hemodialysis and renal transplant patients
with chronic hepatitis C virus”, Transplantation (2005); 80: pp. 1550–1555.
29. Wilson L E, Torbenson M, Astemborski J, et al., “Progression of liver fibrosis among injection drug users with chronic hepatitis”, C Hepatology (2006); 43: pp. 788–795.
30. Sène D , Limal N, Djamila Messous D, et al., “Biological markers of liver fibrosis and activity as non-invasive alternatives
to liver biopsy in patients with chronic hepatitis C and associated mixed cryoglobulinemia vasculitis”, Clin Biochem (2006);
39: pp. 715–721.
31. Myers R P,Tainturier M H, Ratziu V, et al.,“Prediction of liver histological lesions with biochemical markers in patients with
chronic hepatitis B”, J Hepatol (2003), 39: pp. 222–230.
32. Poynard T, Zoulim F, Ratziu V, et al., “Longitudinal assessment of histology surrogate markers (Fibrotest-Actitest) during
lamivudine therapy in patients with chronic hepatitis B infection”, Am J Gast (2005); 100: pp. 1970–1980.
33. Ratziu V, Massard J, Charlotte F, Messous D, Imbert-Bismut F, Bonyhay L,Tahiri M, Munteanu M,Thabut D, Cadranel
JF, Le Bail B, De Ledinghen V, Poynard T, the LIDO Study Group and the CYTOL Study Group Diagnostic value of
biochemical markers (FibroTest-FibroSURE) for the prediction of liver fibrosis in patients with non-alcoholic fatty liver disease.
BMC Gastroenterology 2006, 6:6.
34. Naveau S, Raynard B, Ratziu V, et al.,“The diagnostic value of biomarkers for the prediction of liver fibrosis in patients with
chronic alcoholic liver disease”, Clin Gastroenterol Hepatol (2005); 3: pp. 167–174.
35. Poynard T, Ratziu V, Naveau S, et al., “The diagnostic value of biomarkers (SteatoTest) for the prediction of liver steatosis”,
Comp Hepatol (2005); 4: p. 10.
36. Poynard T, Ratziu V, Naveau S, et al.,“Diagnostic value of two new biomarkers (SteatoTest and NashTest) for the prediction
of steatosis and nonalcoholic steato-hepatitis (NASH)”, J Hepatol (2006); 44: p. 378S.
37. Thabut D, Naveau S, Charlotte F, et al.,“The diagnostic value of biomarkers (AshTest) for the prediction of alcoholic steatohepatitis
in patients with chronic alcoholic liver disease”, J Hepatol (2006); 44: pp. 1175–1185.
38. Poordad F F, “FIBROSpect II: a potential noninvasive test to assess hepatic fibrosis”, Expert Rev Mol Diagn (2004),
4: pp. 593–597.
39. Patel K, Gordon SC, Jacobson I, et al., “Evaluation of a panel of non-invasive serum markers to differentiate mild from
moderate-to-advanced liver fibrosis in chronic hepatitis C patients”, J Hepatol (2004); 41(6): pp. 935–942.
40. Halfon P, Imbert-Bismut F, Messous D, et al.,“A prospective assessment of the inter-laboratory variability of biochemical
markers of fibrosis (FibroTest) and activity (ActiTest) in patients with chronic liver disease”, Comp Hepatol (2002), 1: pp.
3–7.
41. Ferard G, Piton A, Messous D, et al., “Intermethod calibration of alanine aminotransferase (ALT) and gammaglutamyltransferase
(GGT) results: application to Fibrotest and Actitest scores”, Clin Chem Lab Med (2006); 44: pp.
400–6.
42. Bedossa P, Poynard T, “An algorithm for the grading of activity in chronic hepatitis C.The METAVIR Cooperative Study
Group”, Hepatology (1996), 24: pp. 289–293.
43. Imbert-Bismut F, Messous D, Thibaut V, et al.,“Intra-laboratory analytical variability of biochemical markers of fibrosis
(Fibrotest) and activity (Actitest) and reference ranges in healthy blood donors”, Clin Chem Lab Med (2004), 42: pp.
323–333.
44. Munteanu M, Messous D,Thabut D, et al., “Intra-individual fasting versus postprandial variation of biochemical markers of
liver fibrosis (Fibrotest) and activity (Actitest)”, Comp. Hepatol (2004), 3: p. 3.
45. Thabut D, Imbert-Bismut F, Cazals-Athem D, et al., “Diagnostic value of fibrosis biochemical markers (Fibrotest) for the
prediction of portal hypertension in liver disease”, Hepatology (2003), 38: p. 282A (abstract).
46. Poynard T, McHutchison J, Manns M, et al.,“Biochemical surrogate markers of liver fibrosis and activity in a randomized trial
of peginterferon alfa-2b and ribavirin”, Hepatology (2003), 38: pp. 481–492.
