Clinical Application of Non-invasive Diagnostic Tests for Liver Fibrosis

Jung Woo Shin; Neung Hwa Park

doi:10.4166/kjg.2016.68.1.4

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Shin and Park: Clinical Application of Non-invasive Diagnostic Tests for Liver Fibrosis

Review Article

Korean J Gastroenterol 2016;68(1):4-9.

Published online: 4 October 2016

DOI: https://doi.org/10.4166/kjg.2016.68.1.4

Clinical Application of Non-invasive Diagnostic Tests for Liver Fibrosis

Jung Woo Shin, Neung Hwa Park

Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea

Correspondence to: Neung Hwa Park, Department of Internal Medicine, Ulsan University Hospital, 877 Bangeojinsunhwan-doro, Dong-gu, Ulsan 44033, Korea. Tel: +82-52-250-7400, Fax: +82-52-251-8235, E-mail: nhpark@uuh.ulsan.kr

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The diagnostic assessment of liver fibrosis is an important step in the management of patients with chronic liver diseases. Liver biopsy is considered the gold standard to assess necroinflammation and fibrosis. However, recent technical advances have introduced numerous serum biomarkers and imaging tools using elastography as noninvasive alternatives to biopsy. Serum markers can be direct or indirect markers of the fibrosis process. The elastography-based studies include transient elastography, acoustic radiation force imaging, supersonic shear wave imaging and magnetic resonance elastography. As accumulation of clinical data shows that noninvasive tests provide prognostic information of clinical relevance, non-invasive diagnostic tools have been incorporated into clinical guidelines and practice. Here, the authors review noninvasive tests for the diagnosis of liver fibrosis.

Keywords: Diagnosis, Fibrosis, Liver

References

1. 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; 50:1344–1355.

2. The French METAVIR Cooperative Study Group. Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C. Hepatology. 1994; 20:15–20.

3. Asselah T, Marcellin P. Longterm results of treatment with nucleoside and nucleotide analogues (entecavir and tenofovir) for chronic hepatitis B. Clin Liver Dis. 2013; 17:445–450.

4. Chang TT, Liaw YF, Wu SS, et al. Longterm entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B. Hepatology. 2010; 52:886–893.

5. European Association for Study of Liver. EASL Clinical Practice Guidelines: management of hepatitis C virus infection. J Hepatol. 2014; 60:392–420.

6. 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 metaanalysis. Hepatology. 2011; 53:726–736.

7. Zhu X, Wang LC, Chen EQ, et al. Prospective evaluation of FibroScan for the diagnosis of hepatic fibrosis compared with liver biopsy/AST platelet ratio index and FIB-4 in patients with chronic HBV infection. Dig Dis Sci. 2011; 56:2742–2749.

8. 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; 46:32–36.

9. 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; 7:1104–1112.

10. Poynard T, Morra R, Halfon P, et al. Meta-analyses of FibroTest diagnostic value in chronic liver disease. BMC Gastroenterol. 2007; 7:40.

11. 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; 128:343–350.

12. Poynard T, Munteanu M, Deckmyn O, et al. Validation of liver fibrosis biomarker (FibroTest) for assessing liver fibrosis progression: proof of concept and first application in a large population. J Hepatol. 2012; 57:541–548.

13. Musso G, Gambino R, Cassader M, et al. Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med. 2011; 43:617–649.

14. McHutchison JG, Blatt LM, de Medina M, et al. Measurement of serum hyaluronic acid in patients with chronic hepatitis C and its relationship to liver histology. Consensus Interferon Study Group. J Gastroenterol Hepatol. 2000; 15:945–951.

15. Chou R, Wasson N. Blood tests to diagnose fibrosis or cirrhosis in patients with chronic hepatitis C virus infection. Ann Intern Med. 2013; 159:372.

16. Babbs C, Smith A, Hunt LP, et al. Type III procollagen peptide: a marker of disease activity and prognosis in primary biliary cirrhosis. Lancet. 1988; 1:1021–1024.

17. Lee MH, Cheong JY, Um SH, et al. Comparison of surrogate serum markers and transient elastography (Fibroscan) for assessing cirrhosis in patients with chronic viral hepatitis. Dig Dis Sci. 2010; 55:3552–3560.

18. Tanwar S, Trembling PM, Guha IN, et al. Validation of terminal peptide of procollagen III for the detection and assessment of nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease. Hepatology. 2013; 57:103–111.

19. Li J, Rosman AS, Leo MA, et al. Tissue inhibitor of metalloproteinase is increased in the serum of precirrhotic and cirrhotic alcoholic patients and can serve as a marker of fibrosis. Hepatology. 1994; 19:1418–1423.

20. Leroy V, Monier F, Bottari S, et al. 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.

21. Zhu CL, Li WT, Li Y, et al. Serum levels of tissue inhibitor of metalloproteinase-1 are correlated with liver fibrosis in patients with chronic hepatitis B. J Dig Dis. 2012; 13:558–563.

22. Saitou Y, Shiraki K, Yamanaka Y, et al. Noninvasive estimation of liver fibrosis and response to interferon therapy by a serum fibro-genesis marker, YKL-40, in patients with HCV-associated liver disease. World J Gastroenterol. 2005; 11:476–481.

23. Sul AR. Serum liver fibrosis test. J Korean Med Assoc. 2014; 57:704–709.

24. Degos F, Perez P, Roche B, et al. Diagnostic accuracy of FibroScan and comparison to liver fibrosis biomarkers in chronic viral hepatitis: a multicenter prospective study (the FIBROSTIC study). J Hepatol. 2010; 53:1013–1021.

25. Lupsor Platon M, Stefanescu H, Feier D, et al. Performance of unidimensional transient elastography in staging chronic hepatitis C. Results from a cohort of 1,202 biopsied patients from one single center. J Gastrointestin Liver Dis. 2013; 22:157–166.

26. Lupş or M, Badea R, Stefănescu H, et al. Analysis of histopathological changes that influence liver stiffness in chronic hepatitis C. Results from a cohort of 324 patients. J Gastrointestin Liver Dis. 2008; 17:155–163.

27. Zarski JP, Sturm N, Guechot J, et al. Comparison of nine blood tests and transient elastography for liver fibrosis in chronic hepatitis C: the ANRS HCEP-23 study. J Hepatol. 2012; 56:55–62.

28. Sporea I, Sirli R, Deleanu A, et al. Liver stiffness measurements in patients with HBV vs HCV chronic hepatitis: a comparative study. World J Gastroenterol. 2010; 16:4832–4837.

29. Goyal R, Mallick SR, Mahanta M, et al. Fibroscan can avoid liver biopsy in Indian patients with chronic hepatitis B. J Gastroenterol Hepatol. 2013; 28:1738–1745.

30. Kim BK, Kim DY, Han KH, et al. Risk assessment of esophageal variceal bleeding in B-viral liver cirrhosis by a liver stiffness measurement-based model. Am J Gastroenterol. 2011; 106:1654–1662. 1730.

31. Kim SU, Ahn SH, Park JY, et al. Prediction of postoperative hepatic insufficiency by liver stiffness measurement (FibroScan((R))) before curative resection of hepatocellular carcinoma: a pilot study. Hepatol Int. 2008; 2:471–477.

32. Kim SU, Lee JH, Kim DY, et al. Prediction of liver-related events using fibroscan in chronic hepatitis B patients showing advanced liver fibrosis. PLoS One. 2012; 7:e36676.

33. European Association for Study of Liver. Asociacion Latinoamer-icana para el Estudio del Higado. EASL-ALEH Clinical Practice Guidelines: non-invasive tests for evaluation of liver disease severity and prognosis. J Hepatol. 2015; 63:237–264.

34. AASLD/IDSA HCV Guidance Panel. Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology. 2015; 62:932–954.

35. Nierhoff J, Chávez Ortiz AA, Herrmann E, et al. The efficiency of acoustic radiation force impulse imaging for the staging of liver fibrosis: a metaanalysis. Eur Radiol. 2013; 23:3040–3053.

36. Bota S, Herkner H, Sporea I, et al. Meta-analysis: ARFI elastography versus transient elastography for the evaluation of liver fibrosis. Liver Int. 2013; 33:1138–1147.

37. Bavu E, Gennisson JL, Couade M, et al. Noninvasive in vivo liver fibrosis evaluation using supersonic shear imaging: a clinical study on 113 hepatitis C virus patients. Ultrasound Med Biol. 2011; 37:1361–1373.

38. Poynard T, Munteanu M, Luckina E, et al. Liver fibrosis evaluation using real-time shear wave elastography: applicability and diagnostic performance using methods without a gold standard. J Hepatol. 2013; 58:928–935.

39. Singh S, Venkatesh SK, Wang Z, et al. Diagnostic performance of magnetic resonance elastography in staging liver fibrosis: a systematic review and metaanalysis of individual participant data. Clin Gastroenterol Hepatol. 2015; 13:440–451.e6.

40. Huwart L, Sempoux C, Vicaut E, et al. Magnetic resonance elastography for the noninvasive staging of liver fibrosis. Gastroenterology. 2008; 135:32–40.

41. Bohte AE, de Niet A, Jansen L, et al. Non-invasive evaluation of liver fibrosis: a comparison of ultrasound-based transient elastography and MR elastography in patients with viral hepatitis B and C. Eur Radiol. 2014; 24:638–648.

Table 1.

Diagnostic Accuracy of Serum Makers

Test	Parameter	Prognosis	Sensitivity	Specificity	AUROC
Indirect test
APRI	AST, platelet count	Significant fibrosis	81	55	0.77
		Cirrhosis	77	75	0.84
FIB-4	Platelet count, AST, ALT, age	Significant fibrosis	64	68	0.74
		Cirrhosis	90	58	0.87
Fibrotest	Haptoglobin, α2-macroglobulin, apolipoprotein A1,	Significant fibrosis	92	38	0.79
	GGT, bilirubin	Cirrhosis	83	76	0.86
Direct test
P3NP	N-terminal pro-peptide of collagen type III	Significant fibrosis	74	75	0.72
		Cirrhosis	64	66	0.76
TIMP-1	Tissue inhibitor of metalloprotease-1	Significant fibrosis	66	72	0.71
		Cirrhosis	91	65	0.90
YKL-40	Chondrex	Significant fibrosis	78	81	0.81
		Cirrhosis	80	71	0.80

AUROC, area under the receiver operating characteristics curve; APRI, AST to platelet ratio index.

Table 2.

Diagnostic Performance of Transient Elastography in Patients with Hepatitis B and C

Authors	Etiology	F≥2 (%)	F4 (%)	Cut-offs (kPa)	AUROC
Lupş or et al.²⁶	HCV	65		7.4	0.86
			21	11.9	0.94
Degos et al.²⁴	HCV	62		5.2	0.75
			14	12.9	0.90
Zarski et al.²⁷	HCV	47		5.2	0.82
			14	12.9	0.93
Sporea et al.²⁸	HBV	76		7.0	0.65
			5	13.6	0.97
Degos et al.²⁴	HBV	42		5.2	0.78
			19	12.9	0.85
Goyal et al.²⁹	HBV	25		6.0	0.84
			6	11	0.93

AUROC, area under the receiver operating characteristics curve.

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