{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T01:07:06Z","timestamp":1783040826320,"version":"3.54.6"},"reference-count":107,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T00:00:00Z","timestamp":1627430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Non-invasive indexes of liver fibrosis based on blood examinations have been developed for decades, partially replacing liver biopsy examinations. Recently, the concept of liver cirrhosis was revised and converted to \u201ccompensated advanced chronic liver diseases\u201d since the Baveno VI consensus statement in 2015. The term \u201ccompensated advanced chronic liver diseases\u201d was established based on the premise that serum biomarkers were not able to differentiate cirrhosis from severe fibrosis. The difficulty to histologically distinguish cirrhosis from severe fibrosis had been pointed out in 1977, when the definition and nomenclatures of cirrhosis had been determined by the World Health Organization. That was decades before serum biomarkers available at present were investigated. Though we are accustomed to differentiating the fibrosis stage as stage 1, 2, 3 (severe fibrosis), and 4 (cirrhosis), differentiation of cirrhosis from severe fibrosis is difficult even by histopathological examination. The current review will provide readers a framework to revise how to apply serum biomarkers on liver fibrosis staging in an era of the concept of \u201ccompensated advanced chronic liver disease\u201d.<\/jats:p>","DOI":"10.3390\/jcm10153340","type":"journal-article","created":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T11:12:52Z","timestamp":1627470772000},"page":"3340","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Serum Biomarkers of Liver Fibrosis Staging in the Era of the Concept \u201cCompensated Advanced Chronic Liver Disease\u201d"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9390-7565","authenticated-orcid":false,"given":"Koji","family":"Fujita","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita District, Kagawa 761-0793, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Masaki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita District, Kagawa 761-0793, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.jhep.2015.05.022","article-title":"Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension","volume":"63","author":"Faculty","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11567","DOI":"10.3748\/wjg.v21.i41.11567","article-title":"Non-invasive diagnosis of liver fibrosis and cirrhosis","volume":"21","author":"Lurie","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.jhep.2005.10.013","article-title":"Natural history and prognostic indicators of survival in cirrhosis: A systematic review of 118 studies","volume":"44","author":"Pagliaro","year":"2006","journal-title":"J. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1016\/S0140-6736(14)60121-5","article-title":"Liver cirrhosis","volume":"383","author":"Tsochatzis","year":"2014","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1002\/hep.22742","article-title":"Diseases AAftSoL. liver biopsy","volume":"49","author":"Rockey","year":"2009","journal-title":"Hepatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1053\/j.gastro.2004.08.052","article-title":"Serum markers detect the presence of liver fibrosis: A cohort study","volume":"127","author":"Rosenberg","year":"2004","journal-title":"Gastroenterology"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (2015). EASL-ALEH Clinical practice guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis. J. Hepatol., 63, 237\u2013264.","DOI":"10.1016\/j.jhep.2015.04.006"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"The French METAVIR Cooperative Study Group (1994). Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C. Hepatology, 20, 15\u201320.","DOI":"10.1002\/hep.1840200104"},{"key":"ref_9","first-page":"521","article-title":"The morphology of cirrhosis: Definition, nomenclature, and classification","volume":"55","author":"Anthony","year":"1977","journal-title":"Bull. World Health Organ."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1136\/jcp.31.5.395","article-title":"The morphology of cirrhosis. Recommendations on definition, nomenclature, and classification by a working group sponsored by the World Health Organization","volume":"31","author":"Anthony","year":"1978","journal-title":"J. Clin. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1136\/gut.2010.214650","article-title":"Biopsy and non-invasive methods for the diagnosis of liver fibrosis: Does it take two to tango?","volume":"59","author":"Castera","year":"2010","journal-title":"Gut"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.1056\/NEJMra1610570","article-title":"Use of liver imaging and biopsy in clinical practice","volume":"377","author":"Tapper","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1136\/bmj.1.1330.1210","article-title":"Clinical lecture on cirrhosis of the liver","volume":"1","author":"Saundby","year":"1886","journal-title":"Br. Med. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.bpg.2011.02.009","article-title":"Liver cirrhosis","volume":"25","author":"Pinzani","year":"2011","journal-title":"Best. Pract. Res. Clin. Gastroenterol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1056\/NEJM200102153440706","article-title":"Liver biopsy","volume":"344","author":"Bravo","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2614","DOI":"10.1111\/j.1572-0241.2002.06038.x","article-title":"Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection","volume":"97","author":"Regev","year":"2002","journal-title":"Am. J. Gastroenterol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1111\/j.1572-0241.2002.05507.x","article-title":"Diagnosis of chronic liver disease: Reproducibility and validation of liver biopsy","volume":"97","author":"Persico","year":"2002","journal-title":"Am. J. Gastroenterol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1016\/j.hep.2003.09.022","article-title":"Sampling variability of liver fibrosis in chronic hepatitis C","volume":"38","author":"Bedossa","year":"2003","journal-title":"Hepatology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/S0140-6736(86)90883-4","article-title":"Sampling variability and its influence on the diagnostic yield of percutaneous needle biopsy of the liver","volume":"327","author":"Maharaj","year":"1986","journal-title":"Lancet"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1002\/hep.20535","article-title":"Sources of variability in histological scoring of chronic viral hepatitis","volume":"41","author":"Rousselet","year":"2005","journal-title":"Hepatology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.cgh.2010.03.025","article-title":"Complication rate of percutaneous liver biopsies among persons with advanced chronic liver disease in the HALT-C trial","volume":"8","author":"Seeff","year":"2010","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1046\/j.1365-2893.1997.00141.x","article-title":"CLINIVIR cooperative study groups Age and platelet count: A simple index for predicting the presence of histological lesions in patients with antibodies to hepatitis C virus","volume":"4","author":"Poynard","year":"1997","journal-title":"J. Viral Hepat."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1002\/hep.1840190629","article-title":"Classification of chronic hepatitis: Diagnosis, grading and staging","volume":"19","author":"Desmet","year":"1994","journal-title":"Hepatology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1053\/j.gastro.2008.03.003","article-title":"Mechanisms of hepatic fibrogenesis","volume":"134","author":"Friedman","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_25","first-page":"1445","article-title":"Now there are many (stages) where before there was one: In search of a pathophysiological classification of cirrhosis","volume":"51","author":"Friedman","year":"2009","journal-title":"Hepatology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nrgastro.2017.38","article-title":"Mechanisms of hepatic stellate cell activation","volume":"14","author":"Tsuchida","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1002\/hep.21178","article-title":"Development of a simple noninvasive index to predict significant fibrosis in patients with HIV\/HCV coinfection","volume":"43","author":"Sterling","year":"2006","journal-title":"Hepatology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1053\/jhep.2003.50346","article-title":"A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C","volume":"38","author":"Wai","year":"2003","journal-title":"Hepatology"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Fujita, K., Kuroda, N., Morishita, A., Oura, K., Tadokoro, T., Nomura, T., Yoneyama, H., Arai, T., Himoto, T., and Watanabe, S. (2018). Fibrosis staging using direct serum biomarkers is influenced by hepatitis activity grading in Hepatitis C virus infection. J. Clin. Med., 7.","DOI":"10.3390\/jcm7090267"},{"key":"ref_30","first-page":"138","article-title":"Assessment of liver fibrosis before and after antiviral therapy by different serum marker panels in patients with chronic hepatitis C","volume":"33","author":"Gonzalez","year":"2010","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1111\/j.1478-3231.2009.02192.x","article-title":"Validation of FIB-4 and comparison with other simple noninvasive indices for predicting liver fibrosis and cirrhosis in hepatitis B virus-infected patients","volume":"30","author":"Kim","year":"2010","journal-title":"Liver Int."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1002\/hep.29302","article-title":"Comparison of laboratory tests, ultrasound, or magnetic resonance elastography to detect fibrosis in patients with nonalcoholic fatty liver disease: A meta-analysis","volume":"66","author":"Xiao","year":"2017","journal-title":"Hepatology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/jcla.21572","article-title":"Noninvasive diagnosis of liver fibrosis and cirrhosis in chronic sepatitis C patients","volume":"27","author":"Attallah","year":"2013","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1111\/jvh.12563","article-title":"The gamma-glutamyl transpeptidase-to-platelet ratio predicts liver fibrosis and cirrhosis in HBeAg-positive chronic HBV infection patients with high HBV DNA and normal or mildly elevated alanine transaminase levels in China","volume":"23","author":"Li","year":"2016","journal-title":"J. Viral. Hepat."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1111\/j.1572-0241.2006.00411.x","article-title":"Independent prospective multicenter validation of biochemical markers (Fibrotest-Actitest) for the prediction of liver fibrosis and activity in patients with chronic hepatitis C: The fibropaca Study","volume":"101","author":"Halfon","year":"2006","journal-title":"Am. J. Gastroenterol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.jhep.2016.04.023","article-title":"Diagnostic accuracy and prognostic significance of blood fibrosis tests and liver stiffness measurement by FibroScan in non-alcoholic fatty liver disease","volume":"65","author":"Boursier","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"10582","DOI":"10.1038\/s41598-020-67471-y","article-title":"Wisteria floribunda agglutinin-positive Mac-2-binding protein as a diagnostic biomarker in liver cirrhosis: An updated meta-analysis","volume":"10","author":"Feng","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1111\/jvh.12161","article-title":"Performance of enhanced liver fibrosis test and comparison with transient elastography in the identification of liver fibrosis in patients with chronic hepatitis B infection","volume":"21","author":"Trembling","year":"2013","journal-title":"J. Viral Hepat."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1002\/hep.30842","article-title":"Noninvasive tests accurately identify advanced fibrosis due to NASH: Baseline data from the STELLAR trials","volume":"70","author":"Anstee","year":"2019","journal-title":"Hepatology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1002\/hep.21835","article-title":"Diagnostic accuracy of the aspartate aminotransferase-to-platelet ratio index for the prediction of hepatitis C\u2013related fibrosis: A systematic review","volume":"46","author":"Shaheen","year":"2007","journal-title":"Hepatology"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Jin, W., Lin, Z., Xin, Y., Jiang, X., Dong, Q., and Xuan, S. (2012). Diagnostic accuracy of the aspartate aminotransferase-to-platelet ratio index for the prediction of hepatitis B-related fibrosis: A leading meta-analysis. BMC Gastroenterol., 12.","DOI":"10.1186\/1471-230X-12-14"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2589","DOI":"10.1111\/j.1572-0241.2007.01466.x","article-title":"FibroTest and FibroScan for the prediction of hepatitis C-related fibrosis: A systematic review of diagnostic test accuracy","volume":"102","author":"Shaheen","year":"2007","journal-title":"Am. J. Gastroenterol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1038\/ajg.2014.21","article-title":"FibroTest\/Fibrosure for significant liver fibrosis and cirrhosis in chronic hepatitis B: A meta-analysis","volume":"109","author":"Salkic","year":"2014","journal-title":"Am. J. Gastroenterol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.addr.2017.05.007","article-title":"Hepatic stellate cells as key target in liver fibrosis","volume":"121","author":"Higashi","year":"2017","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1002\/hep.27296","article-title":"Cost-effectiveness of noninvasive liver fibrosis tests for treatment decisions in patients with chronic hepatitis C","volume":"60","author":"Tsochatzis","year":"2014","journal-title":"Hepatology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1002\/hep.22085","article-title":"The predictive value of FIB-4 versus FibroTest, APRI, FibroIndex and Forns index to noninvasively estimate fibrosis in hepatitis C and nonhepatitis C liver diseases","volume":"47","author":"Adler","year":"2008","journal-title":"Hepatology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/hep.21669","article-title":"FIB-4: An inexpensive and accurate marker of fibrosis in HCV infection. comparison with liver biopsy and fibrotest","volume":"46","author":"Mallet","year":"2007","journal-title":"Hepatology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1111\/apt.14619","article-title":"Fibrosis-4 index predicts cirrhosis risk and liver-related mortality in 2075 patients with chronic HBV infection","volume":"47","author":"Tseng","year":"2018","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1016\/j.dld.2017.05.002","article-title":"AST to Platelet Ratio Index and fibrosis 4 calculator scores for non-invasive assessment of hepatic fibrosis in patients with non-alcoholic fatty liver disease","volume":"49","author":"Peleg","year":"2017","journal-title":"Dig. Liver Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1038\/ajg.2016.453","article-title":"Age as a Confounding Factor for the Accurate Non-Invasive Diagnosis of Advanced NAFLD Fibrosis","volume":"112","author":"McPherson","year":"2017","journal-title":"Am. J. Gastroenterol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1136\/gutjnl-2014-306842","article-title":"Pathobiology of liver fibrosis: A translational success story","volume":"64","author":"Lee","year":"2015","journal-title":"Gut"},{"key":"ref_52","first-page":"117","article-title":"Real life experiences in HCV management in 2018","volume":"17","author":"Andreoni","year":"2018","journal-title":"Expert Rev. Anti Infect. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1001\/jama.2018.3795","article-title":"Chronic hepatitis B infection: A Review","volume":"319","author":"Tang","year":"2018","journal-title":"JAMA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2742","DOI":"10.1007\/s10620-011-1659-1","article-title":"Prospective evaluation of FibroScan for the diagnosis of hepatic fibrosis compared with liver biopsy\/AST Platelet ratio index and FIB-4 in patients with chronic HBV infection","volume":"56","author":"Zhu","year":"2011","journal-title":"Dig. Dis. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1016\/S0140-6736(00)04258-6","article-title":"Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: A prospective study","volume":"357","author":"Ratziu","year":"2001","journal-title":"Lancet"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1002\/hep.22576","article-title":"Diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with alcoholic liver disease","volume":"49","author":"Naveau","year":"2008","journal-title":"Hepatology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1002\/hep.27305","article-title":"Elevated serum levels of Wisteria floribunda agglutinin-positive human Mac-2 binding protein predict the development of hepatocellular carcinoma in hepatitis C patients","volume":"60","author":"Yamasaki","year":"2014","journal-title":"Hepatology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1080\/14789450.2018.1419066","article-title":"Wisteria floribunda agglutinin positive glycobiomarkers: A unique lectin as a serum biomarker probe in various diseases","volume":"15","author":"Narimatsu","year":"2017","journal-title":"Expert Rev. Proteom."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1007\/s00535-014-0946-y","article-title":"Gotoh, M.; Narimatsu, H.; Korenaga, M.; Mizokami, M.; et al. A novel serum marker, glycosylated Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA(+)-M2BP), for assessing liver fibrosis","volume":"50","author":"Toshima","year":"2015","journal-title":"J. Gastroenterol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1038\/srep01065","article-title":"A serum \u201csweet-doughnut\u201d protein facilitates fibrosis evaluation and therapy assessment in patients with viral hepatitis","volume":"3","author":"Kuno","year":"2013","journal-title":"Sci. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1111\/apt.13431","article-title":"Serum WFA+-M2BP is a non-invasive liver fibrosis marker that can predict the efficacy of direct-acting anti-viral-based triple therapy for chronic hepatitis C","volume":"43","author":"Ura","year":"2015","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1053\/j.gastro.2008.09.013","article-title":"Performance of ELF Serum Markers in Predicting Fibrosis Stage in Pediatric Non-Alcoholic Fatty Liver Disease","volume":"136","author":"Nobili","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.addr.2017.07.014","article-title":"The good and the bad collagens of fibrosis\u2014Their role in signaling and organ function","volume":"121","author":"Karsdal","year":"2017","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1038\/nrm3904","article-title":"Remodelling the extracellular matrix in development and disease","volume":"15","author":"Bonnans","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1002\/ar.23567","article-title":"Basement Membrane Type IV Collagen and Laminin: An Overview of Their Biology and Value as Fibrosis Biomarkers of Liver Disease","volume":"300","author":"Mak","year":"2017","journal-title":"Anat. Rec. Adv. Integr. Anat. Evol. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0174-173X(82)80031-9","article-title":"The Extracellular Matrix of the Liver","volume":"2","author":"Rojkind","year":"1982","journal-title":"Collagen Relat. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"513","DOI":"10.3109\/00365529209000114","article-title":"Significance of serum type-IV collagen levels in various liver diseases. Measurement with a one-step sandwich enzyme immunoassay using monoclonal antibodies with specificity for pepsin-solubilized type-IV collagen","volume":"27","author":"Ueno","year":"1992","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0001-706X(02)00136-5","article-title":"Serum hyaluronic acid as a comprehensive marker to assess severity of liver disease in schistosomiasis","volume":"84","author":"Martins","year":"2002","journal-title":"Acta. Trop."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.patbio.2014.05.019","article-title":"Hyaluronan, a truly \u201cyouthful\u201d polysaccharide. Its medical applications","volume":"63","author":"Robert","year":"2015","journal-title":"Pathol. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1111\/j.1440-1746.1998.tb00608.x","article-title":"Effects of eating on plasma hyaluronan in patients with cirrhosis: Its mechanism and influence on clinical interpretation","volume":"13","author":"Wong","year":"1998","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.clinbiochem.2015.07.019","article-title":"Hyaluronic acid as a non-invasive biomarker of liver fibrosis","volume":"49","author":"Neuman","year":"2016","journal-title":"Clin. Biochem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.plipres.2007.02.001","article-title":"Regulation and biological activities of the autotaxin-LPA axis","volume":"46","author":"Moolenaar","year":"2007","journal-title":"Prog. Lipid Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.canlet.2009.04.029","article-title":"Rapid clearance of the circulating metastatic factor autotaxin by the scavenger receptors of liver sinusoidal endothelial cells","volume":"284","author":"Jansen","year":"2009","journal-title":"Cancer Lett."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1097\/01.mcg.0000225642.90898.0e","article-title":"Both plasma lysophosphatidic acid and serum autotaxin levels are increased in chronic hepatitis C","volume":"41","author":"Watanabe","year":"2007","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1016\/j.cca.2011.03.014","article-title":"Autotaxin as a novel serum marker of liver fibrosis","volume":"412","author":"Nakagawa","year":"2011","journal-title":"Clin. Chim. Acta"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"8159","DOI":"10.1038\/s41598-018-26531-0","article-title":"Serum Autotaxin Is a Useful Disease Progression Marker in Patients with Primary Biliary Cholangitis","volume":"8","author":"Joshita","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/S0140-6736(89)90578-3","article-title":"Something new in liver cirrhosis epidemiology","volume":"334","author":"Melato","year":"1989","journal-title":"Lancet"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1136\/bmj.1.5589.427","article-title":"Cirrhosis of the liver","volume":"1","author":"Read","year":"1968","journal-title":"Br. Med. J."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1053\/gast.2002.33023","article-title":"Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C","volume":"122","author":"Poynard","year":"2002","journal-title":"Gastroenterology"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1053\/gast.2003.50013","article-title":"Histological outcome during long-term lamivudine therapy","volume":"124","author":"Dienstag","year":"2003","journal-title":"Gastroenterology"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.jhep.2004.01.009","article-title":"Decreased fibrosis during corticosteroid therapy of autoimmune hepatitis","volume":"40","author":"Czaja","year":"2004","journal-title":"J. Hepatol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1002\/hep.21260","article-title":"Reversibility of hepatic fibrosis in treated genetic hemochromatosis: A study of 36 cases","volume":"44","author":"Falize","year":"2006","journal-title":"Hepatology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1309\/AJCP2T2OHTAPBTMP","article-title":"Beyond \u201ccirrhosis\u201d: A proposal from the International Liver Pathology Study Group","volume":"137","author":"Hytiroglou","year":"2012","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1016\/S0168-8278(05)80448-9","article-title":"The natural history of varices","volume":"17","author":"Burroughs","year":"1993","journal-title":"J. Hepatol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1016\/0016-5085(90)91168-6","article-title":"Hemodynamic events in a prospective randomized trial of propranolol versus placebo in the prevention of a first variceal hemorrhage","volume":"99","author":"Groszmann","year":"1990","journal-title":"Gastroenterology"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.jhep.2005.07.036","article-title":"Histological-hemodynamic correlation in cirrhosis\u2014A histological classification of the severity of cirrhosis","volume":"44","author":"Nagula","year":"2006","journal-title":"J. Hepatol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1111\/his.12070","article-title":"Cirrhosis histology and Laennec staging system correlate with high portal pressure","volume":"62","author":"Rastogi","year":"2013","journal-title":"Histopathology"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1002\/lt.20857","article-title":"Transient elastography for diagnosis of advanced fibrosis and portal hypertension in patients with hepatitis C recurrence after liver transplantation","volume":"12","author":"Navasa","year":"2006","journal-title":"Liver Transplant."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1002\/hep.21665","article-title":"Liver stiffness measurement predicts severe portal hypertension in patients with HCV-related cirrhosis","volume":"45","author":"Vizzutti","year":"2007","journal-title":"Hepatology"},{"key":"ref_90","first-page":"256","article-title":"Definitions, methodology and therapeutic strategies in portal hypertension. A Consensus Development Workshop, Baveno, Lake Maggiore, Italy, April 5 and 6, 1990","volume":"15","author":"Pascal","year":"1992","journal-title":"J. Hepatol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/S0168-8278(96)80127-9","article-title":"Developing consensus in portal hypertension","volume":"25","year":"1996","journal-title":"J. Hepatol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1016\/S0168-8278(00)80320-7","article-title":"Updating consensus in portal hypertension: Report of the Baveno III Consensus Workshop on definitions, methodology and therapeutic strategies in portal hypertension","volume":"33","year":"2000","journal-title":"J. Hepatol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.jhep.2005.05.009","article-title":"Evolving consensus in portal hypertension. Report of the Baveno IV consensus workshop on methodology of diagnosis and therapy in portal hypertension","volume":"43","year":"2005","journal-title":"J. Hepatol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/j.jhep.2010.06.004","article-title":"Revising consensus in portal hypertension: Report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension","volume":"53","author":"Faculty","year":"2010","journal-title":"J. Hepatol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/0168-8278(95)80226-6","article-title":"Histological grading and staging of chronic hepatitis","volume":"22","author":"Ishak","year":"1995","journal-title":"J. Hepatol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jhep.2008.10.014","article-title":"Liver biopsy: The best, not the gold standard","volume":"50","author":"Bedossa","year":"2009","journal-title":"J. Hepatol."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Poynard, T., Morra, R., Halfon, P., Castera, L., Ratziu, V., Imbert-Bismut, F., Naveau, S., Thabut, D., Lebrec, D., and Zoulim, F. (2007). Meta-analyses of FibroTest diagnostic value in chronic liver disease. BMC Gastroenterol., 7.","DOI":"10.1186\/1471-230X-7-40"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Berzigotti, A., Tsochatzis, E., Boursier, J., Castera, L., Cazzagon, N., Friedrich-Rust, M., Petta, S., and Thiele, M. (2021). Easl Clinical Practice Guidelines (Cpgs) on non-invasive tests for evaluation of liver disease severity and prognosis\u20142020 Update. J. Hepatol., in press.","DOI":"10.1016\/j.jhep.2021.05.025"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/cld.555","article-title":"Biomarkers of liver fibrosis","volume":"7","author":"Morling","year":"2016","journal-title":"Clin. Liver Dis."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.jhep.2008.07.039","article-title":"Exceeding the limits of liver histology markers","volume":"50","author":"Mehta","year":"2009","journal-title":"J. Hepatol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1053\/j.gastro.2018.08.063","article-title":"Burden and cost of gastrointestinal, liver, and pancreatic diseases in the United States: Update 2018","volume":"156","author":"Peery","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/j.jhep.2018.05.011","article-title":"Burden of liver disease in Europe: Epidemiology and analysis of risk factors to identify prevention policies","volume":"69","author":"Pimpin","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1016\/j.transproceed.2019.01.193","article-title":"Effectiveness of noninvasive fibrosis markers for the prediction of hepatocellular carcinoma in chronic hepatitis B and chronic hepatitis B+D induced cirrhosis","volume":"51","author":"Sahin","year":"2019","journal-title":"Transplant. Proc."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1055\/s-2007-1007122","article-title":"Prognosis of hepatocellular carcinoma: The BCLC staging classification","volume":"19","author":"Llovet","year":"1999","journal-title":"Semin. Liver Dis."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1200\/JCO.2014.57.9151","article-title":"Assessment of liver function in patients with hepatocellular carcinoma: A new evidence-based approach\u2014The ALBI grade","volume":"33","author":"Johnson","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1053\/he.2000.5852","article-title":"A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts","volume":"31","author":"Malinchoc","year":"2000","journal-title":"Hepatology"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/j.jhep.2008.02.008","article-title":"Non-invasive evaluation of liver fibrosis using transient elastography","volume":"48","author":"Castera","year":"2008","journal-title":"J. Hepatol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/15\/3340\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:36:20Z","timestamp":1760164580000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/15\/3340"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,28]]},"references-count":107,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["jcm10153340"],"URL":"https:\/\/doi.org\/10.3390\/jcm10153340","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,28]]}}}