Prediction of liver fibrosis progression by non-invasive tests in chronic hepatitis C: The impact of validation
Authors: Giada Sebastiani, Peter Ghali, Phil Wong, Marc Deschenes
Journal: Journal of Hepatology (2012)

13C-Aminopyrine breath test accurately predicts long-term outcome of chronic hepatitis CJournal of HepatologyVol. 56Issue 4PreviewAlthough numerous non-invasive tests are currently available to explore liver function and disease activity in patients with HCV-related chronic diseases, none of these indicate the likelihood of disease progression in the individual patient. We aimed at assessing the prognostic ability of 13C2-aminopyrine breath test (13C-ABT) in the prediction of liver fibrosis progression in patients with HCV chronic hepatitis who prospectively entered a long-term follow-up. Full-Text PDF Reply to: “Prediction of liver fibrosis progression by non-invasive tests in chronic hepatitis C: The impact of validation”Journal of HepatologyVol. 58Issue 4PreviewWe read with interest the comment by Sebastiani et al. on our article on the ability of 13C2-aminopyrine breath test (13C-ABT) to predict the progression of liver fibrosis in patients with hepatitis C virus (HCV)-related chronic hepatitis C [1]. They remarked on the existence of laboratory and instrumental tools [2] other than 13C-ABT, largely validated and even suggested by current guidelines [3], in the prediction of severity of HCV-related liver diseases. Full-Text PDF Open Access We appreciated the article by Rocco et al. about the prognostic ability of 13C2-aminopyrine breath test (13C-ABT) to predict liver fibrosis progression in patients with chronic hepatitis C [[1]Rocco A. de Nucci G. Valente G. Compare D. D’Arienzo A. Cimino L. et al.13C-aminopyrine breath test accurately predicts long-term outcome of chronic hepatitis C.J Hepatol. 2012; 56: 782-787Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar]. The identification of patients with hepatitis C at higher risk of liver fibrosis progression is clinically relevant in order to preferentially focus healthcare resources and antiviral treatment, and to target interventions aimed at preventing end-stage liver complications. The authors conducted one of the few studies evaluating the prognostic ability of a non-invasive method for liver fibrosis by using paired liver biopsies as reference standard with a long-term follow-up. Importantly, they found that 13C-ABT accurately predicts the risk of liver fibrosis progression. We believe that this article deserves several comments. Rocco et al. refers to image techniques for the non-invasive assessment of liver fibrosis, such as transient elastography, as limited by costs, availability and accuracy. However, transient elastography is a widespread tool for the assessment of liver fibrosis and its excellent accuracy for the identification of cirrhosis has been well established by many studies [[2]Sebastiani G. Alberti A. How far is noninvasive assessment of liver fibrosis from replacing liver biopsy in hepatitis C?.J Viral Hepat. 2012; 19: 18-32Crossref PubMed Scopus (37) Google Scholar]. Transient elastography has also proven to predict 5-year clinical outcomes in chronic hepatitis C [[3]Vergniol J. Foucher J. Terrebonne E. Bernard P.H. Le Bail B. Merrouche W. et al.Non-invasive tests for fibrosis and liver stiffness predict 5-year outcomes of patients with chronic hepatitis C.Gastroenterology. 2011; 140: 1970-1979Abstract Full Text Full Text PDF PubMed Scopus (333) Google Scholar]. With respect to serum biomarkers for liver fibrosis, the authors state that they are not yet widely applied in clinical practice and they are not recommended by guidelines. However, serum biomarkers, including AST-to-Platelet Ratio index (APRI) and Fibrotest-Fibrosure®, have shown good performance in chronic hepatitis C. Moreover, they are able to predict long-term clinical outcomes in patients with chronic hepatitis C [3Vergniol J. Foucher J. Terrebonne E. Bernard P.H. Le Bail B. Merrouche W. et al.Non-invasive tests for fibrosis and liver stiffness predict 5-year outcomes of patients with chronic hepatitis C.Gastroenterology. 2011; 140: 1970-1979Abstract Full Text Full Text PDF PubMed Scopus (333) Google Scholar, 4Poynard T. Ngo Y. Perazzo H. Munteanu M. Lebray P. Moussalli J. et al.Prognostic value of liver fibrosis biomarkers: a meta-analysis.Gastroenterol Hepatol. 2011; 7: 445-454PubMed Google Scholar]. APRI is an excellent first line screening test since it has virtually no cost and global availability. A recent meta-analysis indicates that APRI should be regarded as a first-line screening test for liver fibrosis in hepatitis C in countries with limited healthcare resources, and that more expensive tests should demonstrate a clear advantage in terms of performance [[5]Lin Z.H. Xin Y.N. Dong Q.J. Wang Q. Jiang X.J. Zhan S.H. et al.Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis.Hepatology. 2011; 53: 726-736Crossref PubMed Scopus (706) Google Scholar]. Guidelines from the European Association for the Study of the Liver (EASL) have actually recommended the use of serum biomarkers for the diagnosis of significant liver fibrosis in chronic hepatitis C [[6]Craxi A. EASL clinical practice guidelines: management of hepatitis C virus infection.J Hepatol. 2011; 55: 245-264Abstract Full Text Full Text PDF PubMed Scopus (1150) Google Scholar]. Finally, Rocco et al. did not mention three issues that are important when dealing with non-invasive methods for the diagnosis of liver fibrosis: (1) the cost of 13C-ABT as compared to the other non-invasive methods; (2) the relatively small amount of validation studies on 13C-ABT as compared to the other tests (see Table 1); (3) the fact that 13C-ABT is time-consuming (>2 h) and thus unpractical in the busy clinical setting, as compared to transient elastography (<5 min), APRI and Fibrotest-Fibrosure®.Table 1Main validation features of 13C-ABT, APRI, Fibrotest-Fibrosure and transient elastography. Open table in a new tab Considering that both transient elastography and serum biomarkers have been extensively validated, have proven to predict clinical outcomes, and have been recommended by guidelines, we believe that further studies are needed in order to validate 13C-ABT, and to demonstrate a clear advantage in terms of cost and easy accessibility in clinical practice, as compared to more widespread non-invasive tools. We conclude that identification of non-invasive tests able to predict progression of liver fibrosis is of paramount importance in clinical practice. The choice of the non-invasive method should rely on its validation, cost, local availability and guidelines. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.