Skip to main content

Advertisement

SpringerLink
Log in

Noninvasive assessment of hepatic fibrosis in patients with chronic hepatitis C using serum Fourier transform infrared spectroscopy

  • Original Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Assessment of liver fibrosis is of paramount importance to guide the therapeutic strategy in patients with chronic hepatitis C (CHC). In this pilot study, we investigated the potential of serum Fourier transform infrared (FTIR) spectroscopy for differentiating CHC patients with extensive hepatic fibrosis from those without fibrosis. Twenty-three serum samples from CHC patients were selected according to the degree of hepatic fibrosis as evaluated by the FibroTest: 12 from patients with no hepatic fibrosis (F0) and 11 from patients with extensive fibrosis (F3–F4). The FTIR spectra (ten per sample) were acquired in the transmission mode and data homogeneity was tested by cluster analysis to exclude outliers. After selection of the most discriminant wavelengths using an ANOVA-based algorithm, the support vector machine (SVM) method was used as a supervised classification model to classify the spectra into two classes of hepatic fibrosis, F0 and F3–F4. Given the small number of samples, a leave-one-out cross-validation algorithm was used. When SVM was applied to all spectra (n = 230), the sensitivity and specificity of the classifier were 90.1% and 100%, respectively. When SVM was applied to the subset of 219 spectra, i.e., excluding the outliers, the sensitivity and specificity of the classifier were 95.2% and 100%, respectively. This pilot study strongly suggests that the serum from CHC patients exhibits infrared spectral characteristics, allowing patients with extensive fibrosis to be differentiated from those with no hepatic fibrosis.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. NIH (2002) NIH consensus statement on management of hepatitis C: 2002. NIH Consens State Sci Statements 19:1–46

    Google Scholar 

  2. Bedossa P, Dargere D, Paradis V (2003) Sampling variability of liver fibrosis in chronic hepatitis C. Hepatology 38:1449–1457

    Google Scholar 

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

    Article  Google Scholar 

  4. Cadranel JF, Rufat P, Degos F (2000) Practices of liver biopsy in France: results of a prospective nationwide survey. Hepatology 32:477–481

    Article  CAS  Google Scholar 

  5. Manning DS, Afdhal NH (2008) Diagnosis and quantitation of fibrosis. Gastroenterology 134:1670–1681

    Article  CAS  Google Scholar 

  6. Poynard T, Morra R, Ingiliz P, Imbert-Bismut F, Thabut D, Messous D, Munteanu M, Massard J, Benhamou Y, Ratziu V (2008) Biomarkers of liver fibrosis. Adv Clin Chem 46:131–160

    Article  CAS  Google Scholar 

  7. de Ledinghen V, Vergniol J (2008) Transient elastography (fibroscan). Gastroenterol Clin Biol 32:58–67

    Article  Google Scholar 

  8. Huwart L, Sempoux C, Vicaut E, Salameh N, Annet L, Danse E, Peeters F, ter Beek LC, Rahier J, Sinkus R, Horsmans Y, Van Beers BE (2008) Magnetic resonance elastography for the noninvasive staging of liver fibrosis. Gastroenterology 135:32–40

    Article  Google Scholar 

  9. Forns X (2008) Diagnosis of liver fibrosis in 2008. Gastroenterol Clin Biol 32:1–3

    Article  CAS  Google Scholar 

  10. Ly E, Piot O, Durlach A, Bernard P, Manfait M (2009) Differential diagnosis of cutaneous carcinomas by infrared spectral micro-imaging combined with pattern recognition. Analyst 134:1208–1214

    Article  CAS  Google Scholar 

  11. Murali Krishna C, Sockalingum GD, Vidyasagar MS, Manfait M, Fernanades DJ, Vadhiraja BM, Maheedhar K (2008) An overview on applications of optical spectroscopy in cervical cancers. J Cancer Res Ther 4:26–36

    Article  CAS  Google Scholar 

  12. Du JK, Shi JS, Sun XJ, Wang JS, Xu YZ, Wu JG, Zhang YF, Weng SF (2009) Fourier transform infrared spectroscopy of gallbladder carcinoma cell line. Hepatobiliary Pancreat Dis Int 8:75–78

    CAS  Google Scholar 

  13. Babrah J, Babrah J, McCarthy K, Lush RJ, Rye AD, Bessant C, Stone N (2009) Fourier transform infrared spectroscopic studies of T-cell lymphoma, B-cell lymphoid and myeloid leukaemia cell lines. Analyst 134:763–768

    Article  CAS  Google Scholar 

  14. Draux F, Jeannesson P, Gobinet C, Sulle-Suso J, Pijanka J, Sandt C, Dumas P, Manfait M, Sockalingum GD (2009) IR spectroscopy reveals effect of non-cytotoxic doses of antitumour drug on cancer cells. Anal Bioanal Chem 395:2293–2301

    Article  CAS  Google Scholar 

  15. Pijanka JK, Sockalingum GD, Kohler A, Yang Y, Draux F, Parkes P, Lam KP, Collins D, Dumas P, Sandt C, van Pittius D, Douce G, Manfait M, Untereiner V, Sulé-Suso J (2010) Synchrotron based FTIR spectra of stained single cells: towards a clinical application in pathology. Lab Invest 90:797–807

    Article  CAS  Google Scholar 

  16. Essendoubi M, Toubas D, Lepouse C, Leon A, Bourgeade F, Pinon JM, Manfait M, Sockalingum GD (2007) Epidemiological investigation and typing of Candida glabrata clinical isolates by FTIR spectroscopy. J Microbiol Meth 71:325–331

    Article  CAS  Google Scholar 

  17. Budinova G, Salva J, Volka K (1997) Application of molecular spectroscopy in the mid-infrared region to the determination of glucose and cholesterol in whole blood and blood plasma. Appl Spectrosc 51:631–1635

    Article  CAS  Google Scholar 

  18. Shaw RA, Kotowich S, Leroux M, Mantsch HH (1998) Multianalyte plasma analysis using mid-infrared spectroscopy. Ann Clin Biochem 35:624–632

    CAS  Google Scholar 

  19. Petibois C, Rigalleau V, Melin AM, Perromat A, Cazorla G, Gin H, Déléris G (1999) Determination of glucose in dried serum samples by Fourier-transform infrared spectroscopy. Clin Chem 45:1530–1535

    CAS  Google Scholar 

  20. Petibois C, Paiva M, Cazorla G, Déléris G (2002) Discriminant serum biochemical parameters in top class marathon performances. Jpn J Physiol 52:181–190

    Article  CAS  Google Scholar 

  21. Schmitt J, Beekes M, Brauer A, Udelhoven T, Lasch P, Naumann D (2002) Identification of scrapie infection from blood serum by Fourier transform infrared spectroscopy. Anal Chem 74:3865–3868

    Article  CAS  Google Scholar 

  22. Martin TC, Moecks J, Belooussov A, Cawthraw S, Dolenko B, Eiden M, von Frese J, Köhler W, Schmitt J, Somorjai R, Udelhoven S, Verzakov S, Petrich W (2004) Classification of signatures of bovine spongiform encephalopathy in serum using infrared spectroscopy. Analyst 129:897–901

    Article  CAS  Google Scholar 

  23. Staib A, Dolenko B, Fink DJ, Früh J, Nikulin AE, Otto M, Pessin-Minsley MS, Quarder O, Somorjai R, Thienel U, Werner G, Petrich W (2001) Disease pattern recognition testing for rheumatoid arthritis using infrared spectra of human serum. Clin Chem Acta 308:79–89

    Article  CAS  Google Scholar 

  24. Petrov MS, Gordetzov AS, Kukosh MV (2007) Early prediction of severity in acute pancreatitis using infrared spectroscopy of serum. Pancreatology 7:451–458

    Article  Google Scholar 

  25. Imbert-Bismut F, Ratziu V, Pieroni L, Charlotte F, Benhamou Y, Poynard T, MULTIVIRC Group (2001) Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study. Lancet 357:1069–1075

    Article  CAS  Google Scholar 

  26. Haute Autorité de Santé (2006) Non invasive methods for the evaluation of hepatic fibrosis/cirrhosis. Available from www.has-sante.fr

  27. Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, Lok AS (2003) A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology 38:518–526

    Article  Google Scholar 

  28. Forns X, Ampurdanès S, Llovet JM, Aponte J, Quintó L, Martínez-Bauer E, Bruguera M, Sánchez-Tapias JM, Rodés J (2002) Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model. Hepatology 36:986–992

    Google Scholar 

  29. Vallet-Pichard A, Mallet V, Nalpas B, Verkarre V, Nalpas A, Dhalluin-Venier V, Fontaine H, Pol S (2007) FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. Comparison with liver biopsy and FibroTest. Hepatology 46:32–36

    Article  CAS  Google Scholar 

  30. Udelhoven T, Novozhilov M, Schmitt J (2003) The NeuroDeveloperR: a tool for modular neural classification of spectroscopic data. Chemom Intell Lab Syst 66:219–226

    CAS  Google Scholar 

  31. Regev A, Berho M, Jeffers LJ, Milikowski C, Molina EG, Pyrsopoulos NT, Feng ZZ, Reddy KR, Schiff ER (2002) Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection. Am J Gastroenterol 97:2614–2618

    Article  Google Scholar 

  32. Knodell RG, Ishak KG, Black WC, Chen TS, Craig R, Kaplowitz N, Kiernan TW, Wollman J (1981) Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1:431–435

    Article  CAS  Google Scholar 

  33. Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, Denk H, Desmet V, Korb G, MacSween RN, Phillips MJ, Portmann BG, Poulsen H, Scheuer PJ, Schmid M, Thaler H (1995) Histological grading and staging of chronic hepatitis. J Hepatol 22:696–699

    Article  CAS  Google Scholar 

  34. Halfon P, Munteanu M, Poynard T (2008) FibroTest-ActiTest as a non-invasive marker of liver fibrosis. Gastroenterol Clin Biol 32:22–39

    Article  Google Scholar 

  35. Poynard T, Muntenau M, Morra R, Ngo Y, Imbert-Bismut F, Thabut D, Messous D, Massard J, Lebray P, Moussalli J, Benhamou Y, Ratziu V (2008) Methodological aspects of the interpretation of non-invasive biomarkers of liver fibrosis: a 2008 update. Gastroenterol Clin Biol 32(Suppl 1):8–21

    Article  CAS  Google Scholar 

  36. Poynard T, Munteanu M, Imbert-Bismut F, Charlotte F, Thabut D, Le Calvez S, Messous D, Thibault V, Benhamou Y, Moussalli J, Ratziu V (2004) Prospective analysis of discordant results between biochemical markers and biopsy in patients with chronic hepatitis C. Clin Chem 50:1344–1355

    Article  CAS  Google Scholar 

  37. Sebastiani G, Halfon P, Castera L, Pol S, Thomas DL, Mangia A, Di Marco V, Pirisi M, Voiculescu M, Guido M, Bourliere M, Noventa F, Alberti A (2009) SAFE biopsy: a validated method for large-scale staging of liver fibrosis in chronic hepatitis C. Hepatology 49:1821–1827

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Service d’Hépato-Gastroentérologie, Centre Hospitalo-Universitaire de Reims, Hôpital R Debré, 51092, Reims Cedex, France

    Elodie Scaglia & Gérard Thiéfin

  2. Equipe MéDIAN, Université de Reims Champagne-Ardenne, CNRS UMR 6237-MEDyC, UFR de Pharmacie, 51 rue Cognacq-Jay, 51096, Reims Cedex, France

    Ganesh D. Sockalingum, Cyril Gobinet, Michel Manfait & Gérard Thiéfin

  3. Synthon GmbH, Im Neuenheimer Feld 583, 69120, Heidelberg, Germany

    Juergen Schmitt

  4. Laboratoire de Biochimie, Centre Hospitalo-Universitaire de Reims, Hôpital R Debré, 51092, Reims Cedex, France

    Nathalie Schneider

Authors
  1. Elodie Scaglia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ganesh D. Sockalingum
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Juergen Schmitt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cyril Gobinet
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nathalie Schneider
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Michel Manfait
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gérard Thiéfin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gérard Thiéfin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Scaglia, E., Sockalingum, G.D., Schmitt, J. et al. Noninvasive assessment of hepatic fibrosis in patients with chronic hepatitis C using serum Fourier transform infrared spectroscopy. Anal Bioanal Chem 401, 2919–2925 (2011). https://doi.org/10.1007/s00216-011-5402-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-011-5402-8

Keywords

Search

Navigation