- Email: [email protected]
Reply to: “Prediction of liver fibrosis progression by non-invasive tests in chronic hepatitis C: The impact of validation”
Letters to the Editor References
[6] Craxi A. EASL clinical practice guidelines: management of hepatitis C virus infection. J Hepatol 2011;55:245–264.
[1] Rocco A, de Nucci G, Valente G, Compare D, D’Arienzo A, Cimino L, et al. 13Caminopyrine breath test accurately predicts long-term outcome of chronic hepatitis C. J Hepatol 2012;56:782–787. [2] Sebastiani G, Alberti A. How far is noninvasive assessment of liver fibrosis from replacing liver biopsy in hepatitis C? J Viral Hepat 2012;19:18–32. [3] Vergniol J, Foucher J, Terrebonne E, Bernard PH, 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;140:1970–1979. [4] Poynard 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;7:445–454. [5] Lin ZH, Xin YN, Dong QJ, Wang Q, Jiang XJ, Zhan SH, 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;53:726–736.
⇑
Giada Sebastiani Peter Ghali Phil Wong Marc Deschenes Division of Gastroenterology, Royal Victoria Hospital, McGill University Health Centre, Montreal, QC, Canada ⇑Corresponding author. Tel.: +1 5148431421 E-mail address: [email protected]
Reply to: ‘‘Prediction of liver fibrosis progression by non-invasive tests in chronic hepatitis C: The impact of validation’’ To the Editor: 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]. 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. 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]. 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]. 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]. However, they have been proven to predict the outcome of HCV-related chronic disease only in terms of liver-related complications and survival [5-7]. 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 HCVrelated 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 832
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.
Conflict of interest The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. References [1] Rocco A, de Nucci G, Valente G, Compare D, D’Arienzo A, Cimino L, et al. 13 C-aminopyrine breath test accurately predicts long-term outcome of chronic hepatitis C. J Hepatol 2012;56:782–787. [2] Sebastiani G, Alberti A. How far is noninvasive assessment of liver fibrosis from replacing liver biopsy in hepatitis C? J Viral Hepat 2012;19:18–32. [3] European Association for the Study of the Liver. EASL clinical practice guidelines: management of hepatitis C virus infection. J Hepatol 2011;55:245–264. [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;349:825–832. [5] Vergniol J, Foucher J, Terrebonne E, Bernard PH, 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;140:1970–1979. [6] Poynard 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;7:445–454. [7] Lin ZH, Xin YN, Dong QJ, Wang Q, Jiang XJ, Zhan SH, 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;53:726–736.
Alba Rocco Debora Compare ⇑ Gerardo Nardone Department of Clinical and Experimental Medicine, Gastroenterology, University Federico II of Naples, Italy ⇑Corresponding author. Tel./fax: +39 0817464293 E-mail address: [email protected]
Journal of Hepatology 2013 vol. 58 j 831–843
[6] Craxi A. EASL clinical practice guidelines: management of hepatitis C virus infection. J Hepatol 2011;55:245–264.
[1] Rocco A, de Nucci G, Valente G, Compare D, D’Arienzo A, Cimino L, et al. 13Caminopyrine breath test accurately predicts long-term outcome of chronic hepatitis C. J Hepatol 2012;56:782–787. [2] Sebastiani G, Alberti A. How far is noninvasive assessment of liver fibrosis from replacing liver biopsy in hepatitis C? J Viral Hepat 2012;19:18–32. [3] Vergniol J, Foucher J, Terrebonne E, Bernard PH, 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;140:1970–1979. [4] Poynard 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;7:445–454. [5] Lin ZH, Xin YN, Dong QJ, Wang Q, Jiang XJ, Zhan SH, 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;53:726–736.
⇑
Giada Sebastiani Peter Ghali Phil Wong Marc Deschenes Division of Gastroenterology, Royal Victoria Hospital, McGill University Health Centre, Montreal, QC, Canada ⇑Corresponding author. Tel.: +1 5148431421 E-mail address: [email protected]
Reply to: ‘‘Prediction of liver fibrosis progression by non-invasive tests in chronic hepatitis C: The impact of validation’’ To the Editor: 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]. 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. 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]. 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]. 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]. However, they have been proven to predict the outcome of HCV-related chronic disease only in terms of liver-related complications and survival [5-7]. 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 HCVrelated 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 832
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.
Conflict of interest The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. References [1] Rocco A, de Nucci G, Valente G, Compare D, D’Arienzo A, Cimino L, et al. 13 C-aminopyrine breath test accurately predicts long-term outcome of chronic hepatitis C. J Hepatol 2012;56:782–787. [2] Sebastiani G, Alberti A. How far is noninvasive assessment of liver fibrosis from replacing liver biopsy in hepatitis C? J Viral Hepat 2012;19:18–32. [3] European Association for the Study of the Liver. EASL clinical practice guidelines: management of hepatitis C virus infection. J Hepatol 2011;55:245–264. [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;349:825–832. [5] Vergniol J, Foucher J, Terrebonne E, Bernard PH, 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;140:1970–1979. [6] Poynard 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;7:445–454. [7] Lin ZH, Xin YN, Dong QJ, Wang Q, Jiang XJ, Zhan SH, 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;53:726–736.
Alba Rocco Debora Compare ⇑ Gerardo Nardone Department of Clinical and Experimental Medicine, Gastroenterology, University Federico II of Naples, Italy ⇑Corresponding author. Tel./fax: +39 0817464293 E-mail address: [email protected]
Journal of Hepatology 2013 vol. 58 j 831–843