Reply to: “Prediction of liver fibrosis progression by non-invasive tests in chronic hepatitis C: The impact of validation”
Authors: Alba Rocco, Debora Compare, Gerardo Nardone
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 Prediction of liver fibrosis progression by non-invasive tests in chronic hepatitis C: The impact of validationJournal of HepatologyVol. 58Issue 4PreviewWe 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]. 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. Full-Text PDF Open Access We 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]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]. They remarked on the existence of laboratory and instrumental tools [[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] other than 13C-ABT, largely validated and even suggested by current guidelines [[3]European Association for the Study of the Liver 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], in the prediction of severity of HCV-related liver diseases. Liver fibrosis, as evaluated on biopsy samples, is of crucial importance for the diagnosis of severity of liver diseases and is still the best prognosis predictor in patients with HCV-related chronic hepatitis [[4]Poynard T. Bedossa P. Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C: the OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups.Lancet. 1997; 349: 825-832Abstract Full Text Full Text PDF PubMed Scopus (2800) Google Scholar]. The quest for non-invasive procedures able to accurately stage liver fibrosis and to predict outcome has led to various laboratory tests and imaging techniques. However, the rate and speed of fibrosis progression are highly variable, ranging from slow to rapid progression, probably in relation to host characteristics, external factors, co-infections and co-morbidities [[4]Poynard T. Bedossa P. Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C: the OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups.Lancet. 1997; 349: 825-832Abstract Full Text Full Text PDF PubMed Scopus (2800) Google Scholar]. It is noteworthy that one of the major limitations of the invasive and non-invasive methods currently available to stage liver fibrosis is that none can predict the likelihood of disease progression at an early stage of the disease. Transient elastography and serum markers have a high accuracy in the diagnosis of liver fibrosis for which they are recommended by current guidelines [[3]European Association for the Study of the Liver 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]. However, they have been proven to predict the outcome of HCV-related chronic disease only in terms of liver-related complications and survival [5Vergniol J. Foucher J. Terrebonne E. Bernard P.H. le Bail B. Merrouche W. et al.Noninvasive 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, 6Poynard T. Ngo Y. Perazzo H. Munteanu M. Lebray P. Moussalli J. et al.Prognostic value of liver fibrosis biomarkers: a meta-analysis.Gastroenterol Hepatol (N Y). 2011; 7: 445-454PubMed Google Scholar, 7Lin 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]. In contrast, thanks to the experimental design of our study, which included only HCV-infected patients naïve to therapy, in absence of liver cirrhosis and other causes of liver disease, who underwent paired biopsies in a long-term follow-up (mean period 7 years), we were able to demonstrate that the 13C-ABT predicts the likelihood of disease progression at an early stage of the disease. Thus, a comparison between the 13C-ABT and the other tests mentioned by Sebastiani et al. in terms of diagnostic performance and health costs is not feasible. Given the rapidly changing therapeutic landscape of HCV-related chronic diseases, it might become critical to identify who should be treated now and who might best wait for treatment. Thus, in the near future, the early identification of the subgroup of subjects at higher risk of liver fibrosis progression could be decisive in allocating healthcare resources and selecting antiviral treatment. In conclusion, with the premise that further studies would be advisable to further validate 13C-ABT, we believe that this test can be a useful complementary tool to evaluate the outcome of patients chronically infected with HCV. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.