Reply to: Correspondence on “EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 update”

Abstract

An elevated FIB-4 score predicts liver cancer development: A longitudinal analysis from 29,999 patients with NAFLDJournal of HepatologyVol. 76Issue 1PreviewJust recently, the EASL updated their “Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis”, emphasizing the high predictive value and clinical relevance of simple non-invasive tests (NITs), such as the fibrosis-4 (FIB-4) score (calculated on the basis of age, AST/ALT levels and platelet count1) to rule out advanced fibrosis and stratify the risk of liver-related outcomes in patients with non-alcoholic fatty liver disease (NAFLD).2 A higher FiB-4 score should trigger referral to a specialized hepatologist and justify initiation of further hepatological and metabolic work-up as well as potentially therapeutic interventions and regular surveillance. Full-Text PDF EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 updateJournal of HepatologyVol. 75Issue 3PreviewNon-invasive tests are increasingly being used to improve the diagnosis and prognostication of chronic liver diseases across aetiologies. Herein, we provide the latest update to the EASL Clinical Practice Guidelines on the use of non-invasive tests for the evaluation of liver disease severity and prognosis, focusing on the topics for which relevant evidence has been published in the last 5 years. Full-Text PDF Poor performance of FIB-4 in elderly individuals at risk for chronic liver disease – implications for the clinical utility of the EASL NIT guidelineJournal of HepatologyVol. 76Issue 1PreviewWith the identification of novel risk factors for chronic liver disease, the number of patients potentially eligible for referral for hepatologist consultation has expanded rapidly. Hence, non-invasive tools for risk stratification and identification of patients at highest risk are essential. We, therefore, read with great interest the 2021 update of the “EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis”.1 Through the synthesis of available evidence and expert opinion, an algorithm was constructed to aid practitioners in identifying patients at highest risk of significant liver disease. Full-Text PDF Risk stratification of decompensation using liver stiffness and platelet counts in compensated advanced chronic liver disease (CHESS2102)Journal of HepatologyVol. 76Issue 1PreviewThe latest EASL guidelines on non-invasive tests for the evaluation of liver disease severity and prognosis proposed an algorithm for risk stratification in compensated chronic liver disease (CLD) using non-invasive tools.1 Patients with liver stiffness measurement (LSM) <20 kPa and platelet counts (PLT) >150 ×109/L are very unlikely to have varices needing treatment, while those not meeting this criteria are at an increased risk of clinical decompensation.1 LSM is the most validated non-invasive tool for risk stratification in CLD and a cut-off >20-25 kPa could be used to identify patients with clinically significant portal hypertension,2,3 which is closely associated with decompensation in patients with CLD. Full-Text PDF We thank Loosen et al.,[1]Loosen S.H. Kostev K. Keitel K. Tacke F. Roderburg C. Luedde T. An elevated FIB-4 score predicts liver cancer development: a longitudinal analysis from 29,999 NAFLD patients.J Hepatol. 2022; 76: 247-248Abstract Full Text Full Text PDF Scopus (10) Google Scholar van Kleef et al.[2]van Kleef L.A. Sonneveld M.J. de Man R.A. deKnegt R.J. Poor performance of FIB-4 in elderly individuals at risk for chronic liver disease – implications for the clinical utility of the EASL NIT guideline.J Hepatol. 2022; 76: 245-246Abstract Full Text Full Text PDF Scopus (5) Google Scholar and Liu et al.[3]Liu Y. Liu C. Li J. Kim T.H. Enomoto H. Qi X. Risk stratification of decompensation using liver stiffness and platelet counts in 2 compensated advanced chronic liver disease.J Hepatol. 2022; 76: 248-250Abstract Full Text Full Text PDF Scopus (2) Google Scholar for their interest in our work.[4]European Association for the Study of the Liver. et al.European Association for the Study of the Liver- CPG PanelEASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 update.J Hepatol. 2021 Sep; 75: 659-689Abstract Full Text Full Text PDF PubMed Scopus (195) Google Scholar The observation of Loosen et al. that fibrosis-4 (FIB-4) ≥1.3 is associated with an over 12-fold increase in the risk of hepatocellular carcinoma in a large cohort of 29,999 patients with non-alcoholic fatty liver disease (NAFLD) in Germany followed-up between 2005 and 2019 is very important, and confirms previous observations in the Asian population with NAFLD.[5]Kim G.A. Lee H.C. Choe J. Kim M.J. Lee M.J. Chang H.S. et al.Association between non-alcoholic fatty liver disease and cancer incidence rate.J Hepatol. 2018; 68: 140-146Abstract Full Text Full Text PDF Scopus (129) Google Scholar This data underlines that patients with FIB-4 >1.3 should be referred for further evaluation and surveillance, as suggested by our CPGs.On the other hand, van Kleef et al. suggest that FIB-4 is not a reliable first-line test for liver fibrosis assessment in patients ≥65 years old participating in the Rotterdam study, taking liver stiffness measurement (LSM) using vibration controlled transient elastography (VCTE) as a reference standard. In their study, FIB-4 had poor discriminative performance (AUROC 0.635) and missed 40/159 (25.2%) individuals above the age of 65 with LSM ≥8 kPa. The Rotterdam study is a large cohort sampled from a general, unselected population, with available data on liver biochemistry, metabolic syndrome, alcohol consumption, and LSM, and included 3,891 participants of whom 6.0% had LSM ≥8 kPa. However, the study has several drawbacks that we would like to underline. First, and most important, LSM is better at ruling-out rather than ruling-in advanced liver fibrosis, and an LSM ≥8 kPa does not necessarily imply the presence of advanced fibrosis, especially in a random population sample. LSM has suboptimal specificity and positive predictive value (PPV), even more in a context of low prevalence of advanced fibrosis (please see our considerations on the dependency of sensitivity, specificity, PPV and negative predictive value on the prevalence of a given endpoint of interest in the general population in our CPGs[4]European Association for the Study of the Liver. et al.European Association for the Study of the Liver- CPG PanelEASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 update.J Hepatol. 2021 Sep; 75: 659-689Abstract Full Text Full Text PDF PubMed Scopus (195) Google Scholar). Several patients with FIB-4 <1.30 and LSM ≥8.0 kPa would likely not have advanced fibrosis, which leads to an underestimation of the sensitivity of FIB-4 for advanced fibrosis in this work. Indicatively, the specificity of the 8 kPa cut-off for advanced fibrosis in patients with alcohol-related liver disease or NAFLD was 64% in a large multicenter cohort.[6]Papatheodoridi M. Hiriart J.B. Lupsor-Platon M. Bronte F. Boursier J. Elshaarawy O. et al.Refining the Baveno VI elastography criteria for the definition of compensated advanced chronic liver disease.J Hepatol. 2021 May; 74: 1109-1116Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar Since it is not possible to assess the number of patients with advanced fibrosis who would have been missed using FIB-4 in the Rotterdam study (no liver biopsy available), robust endpoints such as the development of liver-related events should be used instead. Longitudinal studies performed in the general population, similar to the Rotterdam cohort, have shown that the prognosis of patients with FIB-4 <1.30 is excellent and, even more, that repeating FIB-4 can refine the prognosis during follow-up.[7]Hagström H. Talbäck M. Andreasson A. Walldius G. Hammar N. Ability of noninvasive scoring systems to identify individuals in the population at risk for severe liver disease.Gastroenterology. 2020; 158: 200-214Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar,[8]Hagström H. Talbäck M. Andreasson A. Walldius G. Hammar N. Repeated FIB-4 measurements can help identify individuals at risk of severe liver disease.J Hepatol. 2020; 73: 1023-1029Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar The letter by Loosen et al.[1]Loosen S.H. Kostev K. Keitel K. Tacke F. Roderburg C. Luedde T. An elevated FIB-4 score predicts liver cancer development: a longitudinal analysis from 29,999 NAFLD patients.J Hepatol. 2022; 76: 247-248Abstract Full Text Full Text PDF Scopus (10) Google Scholar further adds to this body of evidence supporting favorable outcomes in patients with FIB-4 <1.30. Second, performing a FIB-4 examination is indicated in any patient who has risk factors for advanced fibrosis in the context of NAFLD or alcohol-related liver disease rather than in unselected populations. Finally, performing FIB-4 in individuals ≥65 years old is somehow an artificial exercise – many patients would not benefit because of comorbidities and competing risks of mortality.Irrespective of these considerations, in an ideal world, patients with risk factors for chronic liver disease should be evaluated using the best available non-invasive methods for liver fibrosis assessment. We acknowledge that FIB-4 is limited by false negatives and false positives. Future referral pathways and screening programs will have to evolve, for instance taking advantage of the increased availability of point- and 2D-shear wave ultrasound elastography embedded in most high-end ultrasound devices, or of the broader availability of patented serum tests of fibrosis with high accuracy. Until then, we maintain that FIB-4 is the recommended first-line test in current referral pathways due to a good balance between simplicity, availability, price, and a diagnostic accuracy that beats individual routine blood tests and doctor’s clinical acumen alone.[9]Lindvig K.P. Hansen T.L. Madsen B.S. Kjaergaard M. Møller L. Detlefsen S. et al.Diagnostic accuracy of routine liver function tests to identify patients with significant and advanced alcohol-related liver fibrosis.Scand J Gastroenterol. 2021; 56: 1088-1095Crossref PubMed Scopus (4) Google ScholarFinally, beyond diagnostic accuracy and rate of referral, the clinical benefit and utility of algorithms for liver fibrosis screening in patients aged over 65 should ultimately be demonstrated through cost effectiveness studies.Regarding the findings of the retrospective international study reported in the letter of Liu et al.[3]Liu Y. Liu C. Li J. Kim T.H. Enomoto H. Qi X. Risk stratification of decompensation using liver stiffness and platelet counts in 2 compensated advanced chronic liver disease.J Hepatol. 2022; 76: 248-250Abstract Full Text Full Text PDF Scopus (2) Google Scholar in 661 patients with compensated advanced chronic liver disease (cACLD) mostly due to HBV or HCV, the risk of clinical decompensation was found to be low in patients meeting the Baveno VI criteria vs. patients not meeting these criteria; among patients outside the Baveno VI criteria, those with LSM ≥25 kPa had the highest risk of decompensation. These results are in agreement with a large body of evidence showing that LSM holds a strong prognostic value for clinical events in patients with cACLD,[4]European Association for the Study of the Liver. et al.European Association for the Study of the Liver- CPG PanelEASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 update.J Hepatol. 2021 Sep; 75: 659-689Abstract Full Text Full Text PDF PubMed Scopus (195) Google Scholar and also with the current knowledge regarding non-invasive assessment of portal hypertension. Clinically significant portal hypertension (CSPH) is a major driver of clinical decompensation in compensated patients. The Baveno VI criteria include two independent parameters associated with portal hypertension, namely LSM and platelet count. Both parameters are continuous variables, and previous models have nicely shown that the risk of having CSPH increases as LSM increases and platelet count decreases.[10]Abraldes J.G. Bureau C. Stefanescu H. Augustin S. Ney M. Blasco H. et al.Noninvasive tools and risk of clinically significant portal hypertension and varices in compensated cirrhosis: the "Anticipate" study.Hepatology. 2016 Dec; 64: 2173-2184Crossref PubMed Scopus (161) Google Scholar,[11]Pons M. Augustin S. Scheiner B. Guillaume M. Rosselli M. Rodrigues S.G. et al.Noninvasive diagnosis of portal hypertension in patients with compensated advanced chronic liver disease.Am J Gastroenterol. 2021 Apr; 116: 723-732Crossref PubMed Scopus (33) Google Scholar Previous research has also shown that patients with LSM <20 kPa and normal platelet count (>150 G/L) have a low risk of CSPH (very low if LSM is <15 kPa and platelet count is normal).[10]Abraldes J.G. Bureau C. Stefanescu H. Augustin S. Ney M. Blasco H. et al.Noninvasive tools and risk of clinically significant portal hypertension and varices in compensated cirrhosis: the "Anticipate" study.Hepatology. 2016 Dec; 64: 2173-2184Crossref PubMed Scopus (161) Google Scholar,[11]Pons M. Augustin S. Scheiner B. Guillaume M. Rosselli M. Rodrigues S.G. et al.Noninvasive diagnosis of portal hypertension in patients with compensated advanced chronic liver disease.Am J Gastroenterol. 2021 Apr; 116: 723-732Crossref PubMed Scopus (33) Google Scholar On the other hand, 25 kPa is a specific cut-off to rule-in CSPH.[10]Abraldes J.G. Bureau C. Stefanescu H. Augustin S. Ney M. Blasco H. et al.Noninvasive tools and risk of clinically significant portal hypertension and varices in compensated cirrhosis: the "Anticipate" study.Hepatology. 2016 Dec; 64: 2173-2184Crossref PubMed Scopus (161) Google Scholar Patients in between have an intermediate risk of CSPH. The 3 risk categories for clinical decompensation proposed in the letter by Liu et al.[3]Liu Y. Liu C. Li J. Kim T.H. Enomoto H. Qi X. Risk stratification of decompensation using liver stiffness and platelet counts in 2 compensated advanced chronic liver disease.J Hepatol. 2022; 76: 248-250Abstract Full Text Full Text PDF Scopus (2) Google Scholar mirror this concept, and further add to the body of evidence regarding the prognostic value of non-invasive tests in patients with cACLD. We thank Loosen et al.,[1]Loosen S.H. Kostev K. Keitel K. Tacke F. Roderburg C. Luedde T. An elevated FIB-4 score predicts liver cancer development: a longitudinal analysis from 29,999 NAFLD patients.J Hepatol. 2022; 76: 247-248Abstract Full Text Full Text PDF Scopus (10) Google Scholar van Kleef et al.[2]van Kleef L.A. Sonneveld M.J. de Man R.A. deKnegt R.J. Poor performance of FIB-4 in elderly individuals at risk for chronic liver disease – implications for the clinical utility of the EASL NIT guideline.J Hepatol. 2022; 76: 245-246Abstract Full Text Full Text PDF Scopus (5) Google Scholar and Liu et al.[3]Liu Y. Liu C. Li J. Kim T.H. Enomoto H. Qi X. Risk stratification of decompensation using liver stiffness and platelet counts in 2 compensated advanced chronic liver disease.J Hepatol. 2022; 76: 248-250Abstract Full Text Full Text PDF Scopus (2) Google Scholar for their interest in our work.[4]European Association for the Study of the Liver. et al.European Association for the Study of the Liver- CPG PanelEASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 update.J Hepatol. 2021 Sep; 75: 659-689Abstract Full Text Full Text PDF PubMed Scopus (195) Google Scholar The observation of Loosen et al. that fibrosis-4 (FIB-4) ≥1.3 is associated with an over 12-fold increase in the risk of hepatocellular carcinoma in a large cohort of 29,999 patients with non-alcoholic fatty liver disease (NAFLD) in Germany followed-up between 2005 and 2019 is very important, and confirms previous observations in the Asian population with NAFLD.[5]Kim G.A. Lee H.C. Choe J. Kim M.J. Lee M.J. Chang H.S. et al.Association between non-alcoholic fatty liver disease and cancer incidence rate.J Hepatol. 2018; 68: 140-146Abstract Full Text Full Text PDF Scopus (129) Google Scholar This data underlines that patients with FIB-4 >1.3 should be referred for further evaluation and surveillance, as suggested by our CPGs. On the other hand, van Kleef et al. suggest that FIB-4 is not a reliable first-line test for liver fibrosis assessment in patients ≥65 years old participating in the Rotterdam study, taking liver stiffness measurement (LSM) using vibration controlled transient elastography (VCTE) as a reference standard. In their study, FIB-4 had poor discriminative performance (AUROC 0.635) and missed 40/159 (25.2%) individuals above the age of 65 with LSM ≥8 kPa. The Rotterdam study is a large cohort sampled from a general, unselected population, with available data on liver biochemistry, metabolic syndrome, alcohol consumption, and LSM, and included 3,891 participants of whom 6.0% had LSM ≥8 kPa. However, the study has several drawbacks that we would like to underline. First, and most important, LSM is better at ruling-out rather than ruling-in advanced liver fibrosis, and an LSM ≥8 kPa does not necessarily imply the presence of advanced fibrosis, especially in a random population sample. LSM has suboptimal specificity and positive predictive value (PPV), even more in a context of low prevalence of advanced fibrosis (please see our considerations on the dependency of sensitivity, specificity, PPV and negative predictive value on the prevalence of a given endpoint of interest in the general population in our CPGs[4]European Association for the Study of the Liver. et al.European Association for the Study of the Liver- CPG PanelEASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 update.J Hepatol. 2021 Sep; 75: 659-689Abstract Full Text Full Text PDF PubMed Scopus (195) Google Scholar). Several patients with FIB-4 <1.30 and LSM ≥8.0 kPa would likely not have advanced fibrosis, which leads to an underestimation of the sensitivity of FIB-4 for advanced fibrosis in this work. Indicatively, the specificity of the 8 kPa cut-off for advanced fibrosis in patients with alcohol-related liver disease or NAFLD was 64% in a large multicenter cohort.[6]Papatheodoridi M. Hiriart J.B. Lupsor-Platon M. Bronte F. Boursier J. Elshaarawy O. et al.Refining the Baveno VI elastography criteria for the definition of compensated advanced chronic liver disease.J Hepatol. 2021 May; 74: 1109-1116Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar Since it is not possible to assess the number of patients with advanced fibrosis who would have been missed using FIB-4 in the Rotterdam study (no liver biopsy available), robust endpoints such as the development of liver-related events should be used instead. Longitudinal studies performed in the general population, similar to the Rotterdam cohort, have shown that the prognosis of patients with FIB-4 <1.30 is excellent and, even more, that repeating FIB-4 can refine the prognosis during follow-up.[7]Hagström H. Talbäck M. Andreasson A. Walldius G. Hammar N. Ability of noninvasive scoring systems to identify individuals in the population at risk for severe liver disease.Gastroenterology. 2020; 158: 200-214Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar,[8]Hagström H. Talbäck M. Andreasson A. Walldius G. Hammar N. Repeated FIB-4 measurements can help identify individuals at risk of severe liver disease.J Hepatol. 2020; 73: 1023-1029Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar The letter by Loosen et al.[1]Loosen S.H. Kostev K. Keitel K. Tacke F. Roderburg C. Luedde T. An elevated FIB-4 score predicts liver cancer development: a longitudinal analysis from 29,999 NAFLD patients.J Hepatol. 2022; 76: 247-248Abstract Full Text Full Text PDF Scopus (10) Google Scholar further adds to this body of evidence supporting favorable outcomes in patients with FIB-4 <1.30. Second, performing a FIB-4 examination is indicated in any patient who has risk factors for advanced fibrosis in the context of NAFLD or alcohol-related liver disease rather than in unselected populations. Finally, performing FIB-4 in individuals ≥65 years old is somehow an artificial exercise – many patients would not benefit because of comorbidities and competing risks of mortality. Irrespective of these considerations, in an ideal world, patients with risk factors for chronic liver disease should be evaluated using the best available non-invasive methods for liver fibrosis assessment. We acknowledge that FIB-4 is limited by false negatives and false positives. Future referral pathways and screening programs will have to evolve, for instance taking advantage of the increased availability of point- and 2D-shear wave ultrasound elastography embedded in most high-end ultrasound devices, or of the broader availability of patented serum tests of fibrosis with high accuracy. Until then, we maintain that FIB-4 is the recommended first-line test in current referral pathways due to a good balance between simplicity, availability, price, and a diagnostic accuracy that beats individual routine blood tests and doctor’s clinical acumen alone.[9]Lindvig K.P. Hansen T.L. Madsen B.S. Kjaergaard M. Møller L. Detlefsen S. et al.Diagnostic accuracy of routine liver function tests to identify patients with significant and advanced alcohol-related liver fibrosis.Scand J Gastroenterol. 2021; 56: 1088-1095Crossref PubMed Scopus (4) Google Scholar Finally, beyond diagnostic accuracy and rate of referral, the clinical benefit and utility of algorithms for liver fibrosis screening in patients aged over 65 should ultimately be demonstrated through cost effectiveness studies. Regarding the findings of the retrospective international study reported in the letter of Liu et al.[3]Liu Y. Liu C. Li J. Kim T.H. Enomoto H. Qi X. Risk stratification of decompensation using liver stiffness and platelet counts in 2 compensated advanced chronic liver disease.J Hepatol. 2022; 76: 248-250Abstract Full Text Full Text PDF Scopus (2) Google Scholar in 661 patients with compensated advanced chronic liver disease (cACLD) mostly due to HBV or HCV, the risk of clinical decompensation was found to be low in patients meeting the Baveno VI criteria vs. patients not meeting these criteria; among patients outside the Baveno VI criteria, those with LSM ≥25 kPa had the highest risk of decompensation. These results are in agreement with a large body of evidence showing that LSM holds a strong prognostic value for clinical events in patients with cACLD,[4]European Association for the Study of the Liver. et al.European Association for the Study of the Liver- CPG PanelEASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 update.J Hepatol. 2021 Sep; 75: 659-689Abstract Full Text Full Text PDF PubMed Scopus (195) Google Scholar and also with the current knowledge regarding non-invasive assessment of portal hypertension. Clinically significant portal hypertension (CSPH) is a major driver of clinical decompensation in compensated patients. The Baveno VI criteria include two independent parameters associated with portal hypertension, namely LSM and platelet count. Both parameters are continuous variables, and previous models have nicely shown that the risk of having CSPH increases as LSM increases and platelet count decreases.[10]Abraldes J.G. Bureau C. Stefanescu H. Augustin S. Ney M. Blasco H. et al.Noninvasive tools and risk of clinically significant portal hypertension and varices in compensated cirrhosis: the "Anticipate" study.Hepatology. 2016 Dec; 64: 2173-2184Crossref PubMed Scopus (161) Google Scholar,[11]Pons M. Augustin S. Scheiner B. Guillaume M. Rosselli M. Rodrigues S.G. et al.Noninvasive diagnosis of portal hypertension in patients with compensated advanced chronic liver disease.Am J Gastroenterol. 2021 Apr; 116: 723-732Crossref PubMed Scopus (33) Google Scholar Previous research has also shown that patients with LSM <20 kPa and normal platelet count (>150 G/L) have a low risk of CSPH (very low if LSM is <15 kPa and platelet count is normal).[10]Abraldes J.G. Bureau C. Stefanescu H. Augustin S. Ney M. Blasco H. et al.Noninvasive tools and risk of clinically significant portal hypertension and varices in compensated cirrhosis: the "Anticipate" study.Hepatology. 2016 Dec; 64: 2173-2184Crossref PubMed Scopus (161) Google Scholar,[11]Pons M. Augustin S. Scheiner B. Guillaume M. Rosselli M. Rodrigues S.G. et al.Noninvasive diagnosis of portal hypertension in patients with compensated advanced chronic liver disease.Am J Gastroenterol. 2021 Apr; 116: 723-732Crossref PubMed Scopus (33) Google Scholar On the other hand, 25 kPa is a specific cut-off to rule-in CSPH.[10]Abraldes J.G. Bureau C. Stefanescu H. Augustin S. Ney M. Blasco H. et al.Noninvasive tools and risk of clinically significant portal hypertension and varices in compensated cirrhosis: the "Anticipate" study.Hepatology. 2016 Dec; 64: 2173-2184Crossref PubMed Scopus (161) Google Scholar Patients in between have an intermediate risk of CSPH. The 3 risk categories for clinical decompensation proposed in the letter by Liu et al.[3]Liu Y. Liu C. Li J. Kim T.H. Enomoto H. Qi X. Risk stratification of decompensation using liver stiffness and platelet counts in 2 compensated advanced chronic liver disease.J Hepatol. 2022; 76: 248-250Abstract Full Text Full Text PDF Scopus (2) Google Scholar mirror this concept, and further add to the body of evidence regarding the prognostic value of non-invasive tests in patients with cACLD. Please refer to the accompanying ICMJE disclosure forms for further details. Supplementary dataThe following is the supplementary data to this article: Download .pdf (.16 MB) Help with pdf files Multimedia component 1 The following is the supplementary data to this article: Download .pdf (.16 MB) Help with pdf files Multimedia component 1