Ultrasonographic elastometry vs. blood tests for the diagnosis of cirrhosis: A Pyrrhic victory?
Authors: Paul Calès, Jérôme Boursier, Frédéric Oberti
Journal: Journal of Hepatology (2009)

We appreciated the paper by Castera et al., comparing ultrasonographic transient elastometry (TE) and blood tests for the non-invasive diagnosis of cirrhosis [[1]Castera L. Bail B.L. Roudot-Thoraval F. Bernard P.H. Foucher J. Merrouche W. 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: 59-68Abstract Full Text Full Text PDF PubMed Scopus (321) Google Scholar]. The authors should be commended for their use of the intention-to-diagnose principle according to STARD recommendations. However, this paper deserves several comments. Blood tests were not favoured for several reasons. First, common blood tests were used, but not the best performing tests according to direct comparisons performed in a large series [[2]Boursier J. Bacq Y. Halfon P. Leroy V. de Ledinghen V. de Muret A. et al.Improved diagnostic accuracy of blood tests for severe fibrosis and cirrhosis in chronic hepatitis C.Eur J Gastroenterol Hepatol. 2009; 21: 28-38Crossref PubMed Scopus (49) Google Scholar]. Second, the prevalence of cirrhosis was higher (23%) than in a reference population including about 33,000 liver biopsies (12%) [[3]Thein H.H. Yi Q. Dore G.J. Krahn M.D. Estimation of stage-specific fibrosis progression rates in chronic hepatitis C virus infection: a meta-analysis and meta-regression.Hepatology. 2008; 48: 418-431Crossref PubMed Scopus (667) Google Scholar]. Thus, the AUROC of TE was higher (0.96) than that measured in a recent meta-analysis (0.94) [[4]Friedrich-Rust M. Ong M.F. Martens S. Sarrazin C. Bojunga J. Zeuzem S. et al.Performance of transient elastography for the staging of liver fibrosis: a meta-analysis.Gastroenterology. 2008; 134: 960-974Abstract Full Text Full Text PDF PubMed Scopus (1252) Google Scholar], whereas the AUROC of Fibrotest was lower (0.82) than that observed in a meta-analysis (0.90) [[5]Shaheen A.A. Wan A.F. Myers R.P. FibroTest and FibroScan for the prediction of hepatitis C-related fibrosis: a systematic review of diagnostic test accuracy.Am J Gastroenterol. 2007; 102: 2589-2600Crossref PubMed Scopus (317) Google Scholar] and in a large series (0.88) [[2]Boursier J. Bacq Y. Halfon P. Leroy V. de Ledinghen V. de Muret A. et al.Improved diagnostic accuracy of blood tests for severe fibrosis and cirrhosis in chronic hepatitis C.Eur J Gastroenterol Hepatol. 2009; 21: 28-38Crossref PubMed Scopus (49) Google Scholar]. Third, blood tests are usually constructed to diagnose significant fibrosis (i.e. Metavir F ⩾ 2). This diagnostic target calls upon specific cut-offs and specific coefficients for the markers included in the regression score provided by binary logistic regression. When one of the best performing blood tests for significant fibrosis, like FibroMeter, is used for cirrhosis, its AUROC is 0.907 [[2]Boursier J. Bacq Y. Halfon P. Leroy V. de Ledinghen V. de Muret A. et al.Improved diagnostic accuracy of blood tests for severe fibrosis and cirrhosis in chronic hepatitis C.Eur J Gastroenterol Hepatol. 2009; 21: 28-38Crossref PubMed Scopus (49) Google Scholar]. This can be increased to 0.919 by specifically designing the test for cirrhosis (the same markers are included but with different coefficients than those used for significant fibrosis). This was responsible for a significant increase in the rate of correctly classified patients, from 90.9% to 93.0% (p = 0.005) [[2]Boursier J. Bacq Y. Halfon P. Leroy V. de Ledinghen V. de Muret A. et al.Improved diagnostic accuracy of blood tests for severe fibrosis and cirrhosis in chronic hepatitis C.Eur J Gastroenterol Hepatol. 2009; 21: 28-38Crossref PubMed Scopus (49) Google Scholar]. Based on personal data and those provided by Castera et al., the difference between the AUROC of TE – 0.96 (95% CI: 0.93–0.98) – and FibroMeter specific for cirrhosis – 0.92 (0.89–0.95) – is significant (p = 0.04). However, if we consider the TE AUROC provided by a meta-analysis – 0.94 (0.93–0.95) [[4]Friedrich-Rust M. Ong M.F. Martens S. Sarrazin C. Bojunga J. Zeuzem S. et al.Performance of transient elastography for the staging of liver fibrosis: a meta-analysis.Gastroenterology. 2008; 134: 960-974Abstract Full Text Full Text PDF PubMed Scopus (1252) Google Scholar] – the difference is not significant (p = 0.25). Moreover, the rate of misclassified patients by TE was 8% in the Castera paper vs 7.0% with FibroMeter specific for cirrhosis [[2]Boursier J. Bacq Y. Halfon P. Leroy V. de Ledinghen V. de Muret A. et al.Improved diagnostic accuracy of blood tests for severe fibrosis and cirrhosis in chronic hepatitis C.Eur J Gastroenterol Hepatol. 2009; 21: 28-38Crossref PubMed Scopus (49) Google Scholar]. The authors stated, “Overall, the percentage of correctly classified patients in whom liver biopsy could have been avoided was 90%”. However, the authors did not indicate how they calculated this figure. By using 95% predictive values, the rate of avoided liver biopsy was 91.9% with FibroMeter specific for cirrhosis [[6]Cales P. Boursier J. de Ledinghen V. Halfon P. Bacq Y. Leroy V. et al.Evaluation and improvement of a reliable diagnosis of cirrhosis by blood tests.Gastroenterol Clin Biol. 2008; 32: 1050-1060Crossref PubMed Scopus (13) Google Scholar]. The authors also stated, “These results suggest that, given the high accuracy of TE alone, combining TE with serum indexes does not increase diagnostic accuracy for cirrhosis”. We recently observed that the combination of a good performing blood test with TE could significantly decrease the rate of required liver biopsy, as determined by predictive values. Finally, by quoting a relatively old -1998- reference, the authors suggested that the “reproducibility of measurement of some parameters, such as, for instance AST levels or platelet count, is questionable”, whereas “TE has been shown to be a highly reproducible and operator-independent technique”. In fact, recent data have indicated excellent interlaboratory reproducibility for platelets and AST [[7]Cales P. Veillon P. Konate A. Mathieu E. Ternisien C. Chevailler A. et al.Reproducibility of blood tests of liver fibrosis in clinical practice.Clin Biochem. 2008; 41: 10-18Crossref PubMed Scopus (64) Google Scholar]. Other recent works have indicated that the interobserver reproducibility of TE is excellent for cirrhosis but not for the most frequent values of liver stiffness, and that operator expertise could influence certain characteristics of TE [[8]Boursier J. Konate A. Gorea G. Reaud S. Quemener E. Oberti F. et al.Reproducibility of liver stiffness measurement by ultrasonographic elastometry.Clin Gastroenterol Hepatol. 2008; 6: 1263-1269Abstract Full Text Full Text PDF PubMed Scopus (110) Google Scholar]. Therefore, the overall reproducibility is lower for TE than for blood tests. We conclude that the comparative study of Castera et al. is rather a Pyrrhic victory. TE is an excellent diagnostic tool for cirrhosis, but blood tests used as comparator should be adequately quoted. We think that TE combined with a blood test is a well-adapted strategy in hepatology units, whereas a blood test, combining two diagnostic targets – significant fibrosis and cirrhosis – is convenient for other medical actors. This strategy has been practised in our area since April 2004.