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• W2015248972 abstract "We acknowledge the excellent publication by Rosenberg et al1Rosenberg W.M. Voelker M. Thiel R. Becka M. Burt A. Schuppan D. Hubscher S. Roskams T. Pinzani M. Arthur M.J. European Liver Fibrosis GroupSerum markers detect the presence of liver fibrosis a cohort study.Gastroenterology. 2004; 127: 1704-1713Abstract Full Text Full Text PDF PubMed Scopus (848) Google Scholar and share their belief that thoroughly validated, noninvasive serum markers should replace liver biopsy in the first line exploration of liver diseases. However, as the literature on this topic is quickly expanding, it is important that some inaccuracies be corrected as these may impact on the overall discussion of pros and cons of noninvasive vs invasive procedures.2Bissell M.D. Assessing fibrosis without a liver biopsy are we there yet?.Gastroenterology. 2004; 127: 1847-1849Abstract Full Text Full Text PDF PubMed Scopus (35) Google ScholarFirst, validation of a serum marker is a multistep process that should go far beyond the initial step of cross-sectional assessment: longitudinal validation vs. serial liver biopsies is essential in promoting the use of serum markers for follow-up of untreated patients or evaluating the impact of treatment on liver injury.3Poynard T. Imbert-Bismut F. Munteanu M. Messous D. Myers R.P. Thabut D. Ratziu V. Mercadier A. Benhamou Y. Hainque B. Overview of the diagnostic value of biochemical markers of liver fibrosis (FibroTest, HCV-Fibrosure) and necrosis (ActiTest) in patients with chronic hepatitis C.Comp Hepatol. 2004; 3: 8Crossref PubMed Scopus (312) Google Scholar A prospective analysis of the prevalence, causes, and risk factors of discordant results between serum markers and liver biopsy should be performed.4Poynard T. Munteanu M. Imbert-Bismut F. Charlotte F. Thabut D. Le Calvez S. Messous D. Thibault V. Benhamou Y. Moussalli J. Ratziu V. Prospective analysis of discordant results between biochemical markers and biopsy in patients with chronic hepatitis C.Clin Chem. 2004; 50: 1344-1355Crossref PubMed Scopus (278) Google Scholar The definition of pre-analytical and analytical procedures intended to minimize intra and inter-laboratory variability of the results is mandatory for reproducing the test outside the referral center.3Poynard T. Imbert-Bismut F. Munteanu M. Messous D. Myers R.P. Thabut D. Ratziu V. Mercadier A. Benhamou Y. Hainque B. Overview of the diagnostic value of biochemical markers of liver fibrosis (FibroTest, HCV-Fibrosure) and necrosis (ActiTest) in patients with chronic hepatitis C.Comp Hepatol. 2004; 3: 8Crossref PubMed Scopus (312) Google Scholar To the best of our knowledge, with the notable exception of FibroTest, these steps of validation have not been performed for any of the other available serum markers including the one of Rosenberg et al.Second, the usefulness of a serum fibrosis marker would be considerable if it were able to quantify fibrosis in a wide range of frequent liver diseases. Importantly, Rosenberg et al demonstrated the usefulness of their algorithm in 61 patients with hepatitis B (CHB), 61 with alcoholic liver disease (ALD), and in 81 patients with NAFLD. While this is a first step, larger numbers are necessary for a confident validation. The diagnostic value of FibroTest was reported on in 209,5Myers R.P. Tainturier M.H. Ratziu V. Piton A. Thibault V. Imbert-Bismut F. Messous D. Charlotte F. Di Martino V. Benhamou Y. Poynard T. Prediction of liver histological lesions with biochemical markers in patients with chronic hepatitis B.J Hepatol. 2003; 39: 222-230Abstract Full Text Full Text PDF PubMed Scopus (295) Google Scholar 221,6Naveau S. Raynard B. Ratziu V. Abella A. Imbert-Bismut F. Messous D. Beuzen F. Capron F. Thabut D. Munteanu M. Chaput J.C. Poynard T. Biomarkers for the prediction of liver fibrosis in patients with chronic alcoholic liver disease.Clin Gastroenterol Hepatol. 2005; 3: 167-174Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar, 7Callewaert N. Van Vlierberghe H. Van Hecke A. Laroy W. Delanghe J. Contreras R. Noninvasive diagnosis of liver cirrhosis using DNA sequencer-based total serum protein glycomics.Nat Med. 2004; 10: 1-6Crossref Scopus (373) Google Scholar and 130 patients,8Ratziu V. Le Calvez S. Imbert-Bismut F. Messous D. Charlotte F. Bonyhay L. Munteanu M. Poynard T. Diagnostic value of biochemical markers (Fibrotest) for the prediction of liver fibrosis in patients with non-alcoholic fatty liver disease.Hepatology. 2003; 38: 729AGoogle Scholar respectively, which suggests that it is indeed a universal marker of liver fibrosis.Third, a major advantage of a biochemical marker over liver biopsy is its ability to provide a quantification of liver fibrosis on a continuous scale instead of the semiquantitative assessment of histological staging systems. While correctly emphasizing the ability of their test to perform so, Rosenberg et al incorrectly stated that this is not the case for FibroTest, which “fails to determine the severity of fibrosis in approximately 50% of patients.” Sixteen publications (references in 3) and one meta-analysis have demonstrated that FibroTest provides a truly continuous and quantitative assessment of liver fibrosis in 100% of patients without indeterminate cases.3Poynard T. Imbert-Bismut F. Munteanu M. Messous D. Myers R.P. Thabut D. Ratziu V. Mercadier A. Benhamou Y. Hainque B. Overview of the diagnostic value of biochemical markers of liver fibrosis (FibroTest, HCV-Fibrosure) and necrosis (ActiTest) in patients with chronic hepatitis C.Comp Hepatol. 2004; 3: 8Crossref PubMed Scopus (312) Google Scholar We observed prospectively 18% of discordances due to biopsy failure versus 2% due to Fibrotest failure.4Poynard T. Munteanu M. Imbert-Bismut F. Charlotte F. Thabut D. Le Calvez S. Messous D. Thibault V. Benhamou Y. Moussalli J. Ratziu V. Prospective analysis of discordant results between biochemical markers and biopsy in patients with chronic hepatitis C.Clin Chem. 2004; 50: 1344-1355Crossref PubMed Scopus (278) Google Scholar Moreover, ActiTest is the only marker of necroinflammatory activity available thus far.3Poynard T. Imbert-Bismut F. Munteanu M. Messous D. Myers R.P. Thabut D. Ratziu V. Mercadier A. Benhamou Y. Hainque B. Overview of the diagnostic value of biochemical markers of liver fibrosis (FibroTest, HCV-Fibrosure) and necrosis (ActiTest) in patients with chronic hepatitis C.Comp Hepatol. 2004; 3: 8Crossref PubMed Scopus (312) Google ScholarFinally, for any given fibrosis marker, independent validation is paramount. FibroTest is the only marker that has, till now, been independently validated, although the extent of this validation is, again, incorrectly stated by Rosenberg et al. Indeed, numerous studies are now available confirming the excellent diagnostic value of FibroTest in several multicentric studies,3Poynard T. Imbert-Bismut F. Munteanu M. Messous D. Myers R.P. Thabut D. Ratziu V. Mercadier A. Benhamou Y. Hainque B. Overview of the diagnostic value of biochemical markers of liver fibrosis (FibroTest, HCV-Fibrosure) and necrosis (ActiTest) in patients with chronic hepatitis C.Comp Hepatol. 2004; 3: 8Crossref PubMed Scopus (312) Google Scholar, 9Halfon P. Bourliere M. Deydier R. Botta-Fridlund D. Portal I. Renou C. Bertrand J.J. Tran A. Rosenthal A. Rotily M. Sattonet A. Ouzan D. Independent prospective multicenter validation of biochemical markers (Fibrotest-Actitest) for the prediction of liver fibrosis and activity in patients with chronic hepatitis C.Hepatology. 2003; 38 (abstr).: 188ACrossref Google Scholar and when compared to biopsy and glycomic markers7Callewaert N. Van Vlierberghe H. Van Hecke A. Laroy W. Delanghe J. Contreras R. Noninvasive diagnosis of liver cirrhosis using DNA sequencer-based total serum protein glycomics.Nat Med. 2004; 10: 1-6Crossref Scopus (373) Google Scholar or biopsy and elastography.10Castéra L. Vergniol J. Foucher J. Le Bail B. Chanteloup E. Haaser M. Darriet M. Couzigou P. de Lédinghen V. Prospective comparison of transient elastography, fibrotest, apri and liver biopsy for the assessment of fibrosis in chronic hepatitis C.Gastroenterology. 2005; 128: 343-350Abstract Full Text Full Text PDF PubMed Scopus (2023) Google Scholar For meaningful comparisons, analytical recommendations should however be respected.11Poynard T, Imbert-Bismut F, Ratziu V, Myers RP, Di Martino V, Thabut D, Moussalli J, Benhamou Y. Fibrotest even better than liver biopsy? Clin Chem 2003. Electronic letter http://www.clinchem.org/cgi/eletters/49/3/450. Response: (21 March 2003).Google Scholar The statement in the discussion that we used neural network only in our first validation of FibroTest is not correct as we used also logistic regression,12Imbert-Bismut F. Ratziu V. Pieroni L. Charlotte F. Benhamou Y. Poynard T. Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study.Lancet. 2001; 357: 1069-1075Abstract Full Text Full Text PDF PubMed Scopus (1267) Google Scholar with an error in the quoted reference 20.This brings us to the core of the matter, which is, given the accumulation of data in favor of non-invasive serum markers and their diagnostic value and risk/benefit profile, why haven’t we already abandoned the 50-year old dogma of first-line investigation by liver biopsy in diseases such as CHC, CHB, ALD, and NAFLD? In an accompanying editorial, Bissell concludes that “we are getting closer” but does not recommend crossing the Rubicon.2Bissell M.D. Assessing fibrosis without a liver biopsy are we there yet?.Gastroenterology. 2004; 127: 1847-1849Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar Others consider that “many questions must be answered before we can abandon liver biopsy.”13Afdhal N.H. Biopsy or biomarkers is there a gold standard for diagnosis of liver fibrosis?.Clin Chem. 2004; 50: 1299-1300Crossref PubMed Scopus (47) Google Scholar But this ignores the fact that there comes a point where any attempt to answer these questions while using liver biopsy as the method of reference will fail. It will fail because of the intrinsic limitations of liver biopsy: significant sampling error, inability to be performed in large cohorts or to be repeated for the sake of clinical investigations only. Therefore, there is a reasonable chance that we will never get the answers to these many questions.13Afdhal N.H. Biopsy or biomarkers is there a gold standard for diagnosis of liver fibrosis?.Clin Chem. 2004; 50: 1299-1300Crossref PubMed Scopus (47) Google Scholar Is that a reason then to halt what both patients and many physicians outside the hepatological community consider to be a progress in clinical care?In fact many people are already on the other bank of the river. Not surprisingly, the first ones were the inventors of the biomarkers and physicians afraid of severe adverse events of liver biopsy, followed by leaders in HIV-HCV coinfection.14Soriano V. Martin-Carbonero L. Garcia-Samaniego J. Treatment of chronic hepatitis C virus infection we must target the virus or liver fibrosis?.AIDS. 2003; 17: 751-753Crossref PubMed Scopus (34) Google Scholar The French Association for the Study of Liver Disease already stated in 2003 that FibroTest can be used as an alternative to liver biopsy in patients with chronic hepatitis C.15AFEF. Marqueurs de fibrose. http://www.meditis.net/pagepro.asp (15 Octobre 2003).Google Scholar Many patients have also abandoned liver biopsy, as 61,500 people in 12 countries between September 2002 and December 2004 preferred the use of FibroTest-Fibrosure. In France, the number of FibroTests performed in 2004 for CHC was three times higher (25,000) than the usual number of liver biopsies performed for this indication (n = 8000). This is expected to considerably increase access to treatment in patients who need it, which is the ultimate goal we should be pursuing. Many government authorities have also accepted the reimbursement of health care costs of chronic liver diseases without the classical 15 mm liver biopsy sample report.Due to the dramatically insufficient risk-benefit ratio of biopsy (coefficient variation 40%, 0.3% severe adverse events and 3/10,000 mortality) it is surprising that many leaders and associations in the field of hepatology still recommend liver biopsy as the first line investigation for millions of people exposed to the risk of fibrosis. Based on current evidence, a wise recommendation would be a moratorium on liver biopsy as a first line procedure while awaiting studies demonstrating its cost-utility versus biomarkers. Biopsy should not be abandoned. Biopsy as a second line estimate of liver injury should still be indicated for intricate diseases or clinicobiological discordances. We acknowledge the excellent publication by Rosenberg et al1Rosenberg W.M. Voelker M. Thiel R. Becka M. Burt A. Schuppan D. Hubscher S. Roskams T. Pinzani M. Arthur M.J. European Liver Fibrosis GroupSerum markers detect the presence of liver fibrosis a cohort study.Gastroenterology. 2004; 127: 1704-1713Abstract Full Text Full Text PDF PubMed Scopus (848) Google Scholar and share their belief that thoroughly validated, noninvasive serum markers should replace liver biopsy in the first line exploration of liver diseases. However, as the literature on this topic is quickly expanding, it is important that some inaccuracies be corrected as these may impact on the overall discussion of pros and cons of noninvasive vs invasive procedures.2Bissell M.D. Assessing fibrosis without a liver biopsy are we there yet?.Gastroenterology. 2004; 127: 1847-1849Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar First, validation of a serum marker is a multistep process that should go far beyond the initial step of cross-sectional assessment: longitudinal validation vs. serial liver biopsies is essential in promoting the use of serum markers for follow-up of untreated patients or evaluating the impact of treatment on liver injury.3Poynard T. Imbert-Bismut F. Munteanu M. Messous D. Myers R.P. Thabut D. Ratziu V. Mercadier A. Benhamou Y. Hainque B. Overview of the diagnostic value of biochemical markers of liver fibrosis (FibroTest, HCV-Fibrosure) and necrosis (ActiTest) in patients with chronic hepatitis C.Comp Hepatol. 2004; 3: 8Crossref PubMed Scopus (312) Google Scholar A prospective analysis of the prevalence, causes, and risk factors of discordant results between serum markers and liver biopsy should be performed.4Poynard T. Munteanu M. Imbert-Bismut F. Charlotte F. Thabut D. Le Calvez S. Messous D. Thibault V. Benhamou Y. Moussalli J. Ratziu V. Prospective analysis of discordant results between biochemical markers and biopsy in patients with chronic hepatitis C.Clin Chem. 2004; 50: 1344-1355Crossref PubMed Scopus (278) Google Scholar The definition of pre-analytical and analytical procedures intended to minimize intra and inter-laboratory variability of the results is mandatory for reproducing the test outside the referral center.3Poynard T. Imbert-Bismut F. Munteanu M. Messous D. Myers R.P. Thabut D. Ratziu V. Mercadier A. Benhamou Y. Hainque B. Overview of the diagnostic value of biochemical markers of liver fibrosis (FibroTest, HCV-Fibrosure) and necrosis (ActiTest) in patients with chronic hepatitis C.Comp Hepatol. 2004; 3: 8Crossref PubMed Scopus (312) Google Scholar To the best of our knowledge, with the notable exception of FibroTest, these steps of validation have not been performed for any of the other available serum markers including the one of Rosenberg et al. Second, the usefulness of a serum fibrosis marker would be considerable if it were able to quantify fibrosis in a wide range of frequent liver diseases. Importantly, Rosenberg et al demonstrated the usefulness of their algorithm in 61 patients with hepatitis B (CHB), 61 with alcoholic liver disease (ALD), and in 81 patients with NAFLD. While this is a first step, larger numbers are necessary for a confident validation. The diagnostic value of FibroTest was reported on in 209,5Myers R.P. Tainturier M.H. Ratziu V. Piton A. Thibault V. Imbert-Bismut F. Messous D. Charlotte F. Di Martino V. Benhamou Y. Poynard T. Prediction of liver histological lesions with biochemical markers in patients with chronic hepatitis B.J Hepatol. 2003; 39: 222-230Abstract Full Text Full Text PDF PubMed Scopus (295) Google Scholar 221,6Naveau S. Raynard B. Ratziu V. Abella A. Imbert-Bismut F. Messous D. Beuzen F. Capron F. Thabut D. Munteanu M. Chaput J.C. Poynard T. Biomarkers for the prediction of liver fibrosis in patients with chronic alcoholic liver disease.Clin Gastroenterol Hepatol. 2005; 3: 167-174Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar, 7Callewaert N. Van Vlierberghe H. Van Hecke A. Laroy W. Delanghe J. Contreras R. Noninvasive diagnosis of liver cirrhosis using DNA sequencer-based total serum protein glycomics.Nat Med. 2004; 10: 1-6Crossref Scopus (373) Google Scholar and 130 patients,8Ratziu V. Le Calvez S. Imbert-Bismut F. Messous D. Charlotte F. Bonyhay L. Munteanu M. Poynard T. Diagnostic value of biochemical markers (Fibrotest) for the prediction of liver fibrosis in patients with non-alcoholic fatty liver disease.Hepatology. 2003; 38: 729AGoogle Scholar respectively, which suggests that it is indeed a universal marker of liver fibrosis. Third, a major advantage of a biochemical marker over liver biopsy is its ability to provide a quantification of liver fibrosis on a continuous scale instead of the semiquantitative assessment of histological staging systems. While correctly emphasizing the ability of their test to perform so, Rosenberg et al incorrectly stated that this is not the case for FibroTest, which “fails to determine the severity of fibrosis in approximately 50% of patients.” Sixteen publications (references in 3) and one meta-analysis have demonstrated that FibroTest provides a truly continuous and quantitative assessment of liver fibrosis in 100% of patients without indeterminate cases.3Poynard T. Imbert-Bismut F. Munteanu M. Messous D. Myers R.P. Thabut D. Ratziu V. Mercadier A. Benhamou Y. Hainque B. Overview of the diagnostic value of biochemical markers of liver fibrosis (FibroTest, HCV-Fibrosure) and necrosis (ActiTest) in patients with chronic hepatitis C.Comp Hepatol. 2004; 3: 8Crossref PubMed Scopus (312) Google Scholar We observed prospectively 18% of discordances due to biopsy failure versus 2% due to Fibrotest failure.4Poynard T. Munteanu M. Imbert-Bismut F. Charlotte F. Thabut D. Le Calvez S. Messous D. Thibault V. Benhamou Y. Moussalli J. Ratziu V. Prospective analysis of discordant results between biochemical markers and biopsy in patients with chronic hepatitis C.Clin Chem. 2004; 50: 1344-1355Crossref PubMed Scopus (278) Google Scholar Moreover, ActiTest is the only marker of necroinflammatory activity available thus far.3Poynard T. Imbert-Bismut F. Munteanu M. Messous D. Myers R.P. Thabut D. Ratziu V. Mercadier A. Benhamou Y. Hainque B. Overview of the diagnostic value of biochemical markers of liver fibrosis (FibroTest, HCV-Fibrosure) and necrosis (ActiTest) in patients with chronic hepatitis C.Comp Hepatol. 2004; 3: 8Crossref PubMed Scopus (312) Google Scholar Finally, for any given fibrosis marker, independent validation is paramount. FibroTest is the only marker that has, till now, been independently validated, although the extent of this validation is, again, incorrectly stated by Rosenberg et al. Indeed, numerous studies are now available confirming the excellent diagnostic value of FibroTest in several multicentric studies,3Poynard T. Imbert-Bismut F. Munteanu M. Messous D. Myers R.P. Thabut D. Ratziu V. Mercadier A. Benhamou Y. Hainque B. Overview of the diagnostic value of biochemical markers of liver fibrosis (FibroTest, HCV-Fibrosure) and necrosis (ActiTest) in patients with chronic hepatitis C.Comp Hepatol. 2004; 3: 8Crossref PubMed Scopus (312) Google Scholar, 9Halfon P. Bourliere M. Deydier R. Botta-Fridlund D. Portal I. Renou C. Bertrand J.J. Tran A. Rosenthal A. Rotily M. Sattonet A. Ouzan D. Independent prospective multicenter validation of biochemical markers (Fibrotest-Actitest) for the prediction of liver fibrosis and activity in patients with chronic hepatitis C.Hepatology. 2003; 38 (abstr).: 188ACrossref Google Scholar and when compared to biopsy and glycomic markers7Callewaert N. Van Vlierberghe H. Van Hecke A. Laroy W. Delanghe J. Contreras R. Noninvasive diagnosis of liver cirrhosis using DNA sequencer-based total serum protein glycomics.Nat Med. 2004; 10: 1-6Crossref Scopus (373) Google Scholar or biopsy and elastography.10Castéra L. Vergniol J. Foucher J. Le Bail B. Chanteloup E. Haaser M. Darriet M. Couzigou P. de Lédinghen V. Prospective comparison of transient elastography, fibrotest, apri and liver biopsy for the assessment of fibrosis in chronic hepatitis C.Gastroenterology. 2005; 128: 343-350Abstract Full Text Full Text PDF PubMed Scopus (2023) Google Scholar For meaningful comparisons, analytical recommendations should however be respected.11Poynard T, Imbert-Bismut F, Ratziu V, Myers RP, Di Martino V, Thabut D, Moussalli J, Benhamou Y. Fibrotest even better than liver biopsy? Clin Chem 2003. Electronic letter http://www.clinchem.org/cgi/eletters/49/3/450. Response: (21 March 2003).Google Scholar The statement in the discussion that we used neural network only in our first validation of FibroTest is not correct as we used also logistic regression,12Imbert-Bismut F. Ratziu V. Pieroni L. Charlotte F. Benhamou Y. Poynard T. Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study.Lancet. 2001; 357: 1069-1075Abstract Full Text Full Text PDF PubMed Scopus (1267) Google Scholar with an error in the quoted reference 20. This brings us to the core of the matter, which is, given the accumulation of data in favor of non-invasive serum markers and their diagnostic value and risk/benefit profile, why haven’t we already abandoned the 50-year old dogma of first-line investigation by liver biopsy in diseases such as CHC, CHB, ALD, and NAFLD? In an accompanying editorial, Bissell concludes that “we are getting closer” but does not recommend crossing the Rubicon.2Bissell M.D. Assessing fibrosis without a liver biopsy are we there yet?.Gastroenterology. 2004; 127: 1847-1849Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar Others consider that “many questions must be answered before we can abandon liver biopsy.”13Afdhal N.H. Biopsy or biomarkers is there a gold standard for diagnosis of liver fibrosis?.Clin Chem. 2004; 50: 1299-1300Crossref PubMed Scopus (47) Google Scholar But this ignores the fact that there comes a point where any attempt to answer these questions while using liver biopsy as the method of reference will fail. It will fail because of the intrinsic limitations of liver biopsy: significant sampling error, inability to be performed in large cohorts or to be repeated for the sake of clinical investigations only. Therefore, there is a reasonable chance that we will never get the answers to these many questions.13Afdhal N.H. Biopsy or biomarkers is there a gold standard for diagnosis of liver fibrosis?.Clin Chem. 2004; 50: 1299-1300Crossref PubMed Scopus (47) Google Scholar Is that a reason then to halt what both patients and many physicians outside the hepatological community consider to be a progress in clinical care? In fact many people are already on the other bank of the river. Not surprisingly, the first ones were the inventors of the biomarkers and physicians afraid of severe adverse events of liver biopsy, followed by leaders in HIV-HCV coinfection.14Soriano V. Martin-Carbonero L. Garcia-Samaniego J. Treatment of chronic hepatitis C virus infection we must target the virus or liver fibrosis?.AIDS. 2003; 17: 751-753Crossref PubMed Scopus (34) Google Scholar The French Association for the Study of Liver Disease already stated in 2003 that FibroTest can be used as an alternative to liver biopsy in patients with chronic hepatitis C.15AFEF. Marqueurs de fibrose. http://www.meditis.net/pagepro.asp (15 Octobre 2003).Google Scholar Many patients have also abandoned liver biopsy, as 61,500 people in 12 countries between September 2002 and December 2004 preferred the use of FibroTest-Fibrosure. In France, the number of FibroTests performed in 2004 for CHC was three times higher (25,000) than the usual number of liver biopsies performed for this indication (n = 8000). This is expected to considerably increase access to treatment in patients who need it, which is the ultimate goal we should be pursuing. Many government authorities have also accepted the reimbursement of health care costs of chronic liver diseases without the classical 15 mm liver biopsy sample report. Due to the dramatically insufficient risk-benefit ratio of biopsy (coefficient variation 40%, 0.3% severe adverse events and 3/10,000 mortality) it is surprising that many leaders and associations in the field of hepatology still recommend liver biopsy as the first line investigation for millions of people exposed to the risk of fibrosis. Based on current evidence, a wise recommendation would be a moratorium on liver biopsy as a first line procedure while awaiting studies demonstrating its cost-utility versus biomarkers. Biopsy should not be abandoned. Biopsy as a second line estimate of liver injury should still be indicated for intricate diseases or clinicobiological discordances. ReplyGastroenterologyVol. 128Issue 4PreviewWhile we are flattered by the compliment made by Poynard et al, they have misquoted us. We did not state that “non-invasive markers should replace liver biopsy in the first line exploration of liver diseases.” In fact, we took considerable care to avoid making such a claim as we do not think it would be justified by the results of ours, or others’ studies so far. Full-Text PDF" @default.
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