Open Access Review

Liver fibrosis from viral hepatitis: advances in non-invasive diagnosis

by Jincheng Wang a orcid Jinyu Sun a orcid Tao Qin a Xiaohan Ren a Jin Zhang b orcid  and  Xiaojie Lu a,*
Department of General Surgery, Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University,Nanjing, Jiangsu, China
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, 39216, USA
Author to whom correspondence should be addressed.
CI  2023, 16; 2(1), 16;
Received: 22 March 2023 / Accepted: 22 May 2023 / Published Online: 14 June 2023


The stages of liver fibrosis can reflect the severity of chronic viral hepatitis and the probability of liver cancer. Biopsy is still regarded as the reference for staging fibrosis, but the invasive method is not suitable for first-line screening. In recent years, noninvasive methods for detecting virus-driven liver fibrosis have been developed rapidly, which mainly include biological (serum biomarkers indexes) and physical (imaging assessment of liver stiffness) strategies. In this review, we introduce these noninvasive methods, enumerate their diagnosis performances and discuss the role of ferroptosis. At last, we propose directions for future researches.

Copyright: © 2023 by Wang, Sun, Qin, Ren, Zhang and Lu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (Creative Commons Attribution 4.0 International License). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Show Figures


the Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang Province (YXJR202002,toJ.W)

Share and Cite

ACS Style
Wang, J.; Sun, J.; Qin, T.; Ren, X.; Zhang, J.; Lu, X. Liver fibrosis from viral hepatitis: advances in non-invasive diagnosis. Cancer Insight, 2023, 2, 16.
AMA Style
Wang J, Sun J, Qin T, Ren X, Zhang J, Lu X. Liver fibrosis from viral hepatitis: advances in non-invasive diagnosis. Cancer Insight; 2023, 2(1):16.
Chicago/Turabian Style
Wang, Jincheng; Sun, Jinyu; Qin, Tao; Ren, Xiaohan; Zhang, Jin; Lu, Xiaojie 2023. "Liver fibrosis from viral hepatitis: advances in non-invasive diagnosis" Cancer Insight 2, no.1:16.
APA style
Wang, J., Sun, J., Qin, T., Ren, X., Zhang, J., & Lu, X. (2023). Liver fibrosis from viral hepatitis: advances in non-invasive diagnosis. Cancer Insight, 2(1), 16.

Article Metrics

Article Access Statistics


  1. TrepoC,ChanHL,LokA:HepatitisBvirusinfection.Lancet2014,384(9959):2053-2063.
  2. ShepardCW,FinelliL,AlterMJ:GlobalepidemiologyofhepatitisCvirusinfection.LancetInfectDis2005, 5(9):558-567.
  3. YouH,WangX,MaL,ZhangF,ZhangH,WangY,PanX,ZhengK,KongF,TangR:Insightsintotheimpactof hepatitisBvirusonhepaticstellatecellactivation.CellCommunSignal2023,21(1):70.
  4. RockeyDC,FriedmanSL:FibrosisRegressionAfterEradicationofHepatitisCVirus:From BenchtoBedside. Gastroenterology2021,160(5):1502-1520e1501.
  5. El-Serag HB:Epidemiology of viralhepatitis and hepatocellular carcinoma.Gastroenterology 2012, 142(6):1264-1273e1261.
  6. TsochatzisEA,BoschJ,BurroughsAK:Livercirrhosis.Lancet2014,383(9930):1749-1761.
  7. LeeYA,WallaceMC,FriedmanSL:Pathobiologyofliverfibrosis:atranslationalsuccessstory.Gut2015, 64(5):830-841.
  8. FriedmanSL:Mechanismsofhepaticfibrogenesis.Gastroenterology2008,134(6):1655-1669.
  9. CosconeaS,FontaineH,MeritetJF,CorougeM,SogniP,Vallet-PichardA,MalletV,LegendreC,PolS:Benefits associatedwithantiviraltreatmentinkidneyallograftrecipientswithchronichepatitisBvirusinfection.J Hepatol2012,57(1):55-60.
  10. BravoAA,ShethSG,ChopraS:Liverbiopsy.NEnglJMed2001,344(7):495-500.
  11. RockeyDC,CaldwellSH,GoodmanZD,NelsonRC,SmithAD:Liverbiopsy.Hepatology2009,49(3):1017-1044.
  12. TheodossiA,SkeneAM,PortmannB,Knill-JonesRP,PatrickRS,TateRA,KealeyW,JarvisKJ,O'BrianDJ,WilliamsR: Observervariationinassessmentofliverbiopsiesincludinganalysisbykappastatistics.Gastroenterology 1980,79(2):232-241.
  13. Standish RA,CholongitasE,Dhillon A,BurroughsAK,Dhillon AP:An appraisalofthe histopathological assessmentofliverfibrosis.Gut2006,55(4):569-578.
  14. CasteraL,NegreI,SamiiK,BuffetC:Painexperiencedduringpercutaneousliverbiopsy.Hepatology1999, 30(6):1529-1530.
  15. Moehler M, Sanwald B, Kanzler S, Wanitschke R, Galle PR, Helmreich-Becker I: Hemobilia after minilaparoscopicliverbiopsy:ararecomplication.Endoscopy2000,32(9):S60.
  16. LoIudiceT,BuhacI,BalintJ:Septicemiaasacomplicationofpercutaneousliverbiopsy.Gastroenterology1977, 72(5Pt1):949-951.
  17. KwonTK,JeonSH,ParkHW,JungWJ,HwangJY,ParkKS,ChoKB,HwangJS,AhnSH,ParkSK:[A caseof intraluminalgallbladder hematoma after percutaneous liver biopsy].Taehan Kan Hakhoe Chi2002, 8(4):486-489.
  18. Kuo V, Mubarak A: An unusual complication of a transjugular liver biopsy .Gastroenterology 2014, 146 (3):620-873.
  19. Bedossa P, Poynard T: An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group .Hepatology 1996, 24 (2):289-293.
  20. European Association for Study of L, Asociacion Latinoamericana para el Estudio del H: EASL-ALEH Clinical Practice Guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis .JHepatol 2015, 63 (1):237-264.
  21. Gangadharan B, Antrobus R, Dwek RA, Zitzmann N: Novel serum biomarker candidates for liver fibrosis in hepatitis Cpatients .Clin Chem 2007, 53 (10):1792-1799.
  22. Fontana RJ, Dienstag JL, Bonkovsky HL, Sterling RK, Naishadham D, Goodman ZD, Lok AS, Wright EC, Su GL, Group H-CT: Serum fibrosis markers are associated with liver disease progression in non-responder patients with chronic hepatitis C.Gut 2010, 59 (10):1401-1409.
  23. Malik R, Schuppan D: Serum fibrosis markers to predict clinical and histological progression in hepatitis C non-responders .Gut 2010, 59 (10):1312-1313.
  24. Imbert-Bismut F,Ratziu V,Pieroni L,Charlotte F,Benhamou Y,Poynard T,Group M: Biochemical markers of liver fibrosis in patients with hepatitis Cvirus infection: aprospective study .Lancet 2001, 357 (9262):1069-1075.
  25. Forns X, Ampurdanes S,Llovet JM, Aponte J,Quinto L, Martinez-Bauer E, Bruguera M, Sanchez-Tapias JM, Rodes J: Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model . Hepatology 2002, 36 (4 Pt 1):986-992.
  26. Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, Lok AS: A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C.Hepatology 2003, 38 (2):518-526.
  27. Patel K, Gordon SC, Jacobson I,Hezode C, Oh E, Smith KM, Pawlotsky JM, McHutchison JG: Evaluation of apanel of non-invasive serum markers to differentiate mild from moderate-to-advanced liver fibrosis in chronic hepatitis Cpatients .JHepatol 2004, 41 (6):935-942.
  28. Rosenberg WM, Voelker M, Thiel R, Becka M, Burt A, Schuppan D, Hubscher S,Roskams T,Pinzani M, Arthur MJ et al:Serum markers detect the presence of liver fibrosis: a cohort study .Gastroenterology 2004, 127 (6):1704-1713.
  29. Sud A, Hui JM, Farrell GC, Bandara P,Kench JG, Fung C, Lin R, Samarasinghe D, Liddle C, McCaughan GW et al: Improved prediction of fibrosis in chronic hepatitis Cusing measures of insulin resistance in aprobability index .Hepatology 2004, 39 (5):1239-1247.
  30. Adams LA, Bulsara M, Rossi E, DeBoer B, Speers D, George J,Kench J,Farrell G, McCaughan GW, Jeffrey GP: Hepascore: an accurate validated predictor of liver fibrosis in chronic hepatitis Cinfection .Clin Chem 2005, 51 (10):1867-1873.
  31. Cales P,Oberti F,Michalak S,Hubert-Fouchard I,Rousselet MC, Konate A, Gallois Y,Ternisien C, Chevailler A, Lunel F:Anovel panel of blood markers to assess the degree of liver fibrosis .Hepatology 2005, 42 (6):1373-1381.
  32. Lok AS, Ghany MG, Goodman ZD, Wright EC, Everson GT, Sterling RK, Everhart JE, Lindsay KL, Bonkovsky HL, Di Bisceglie AM et al:Predicting cirrhosis in patients with hepatitis Cbased on standard laboratory tests: results of the HALT-C cohort .Hepatology 2005, 42 (2):282-292.
  33. Islam S, Antonsson L, Westin J,Lagging M: Cirrhosis in hepatitis Cvirus-infected patients can be excluded using an index of standard biochemical serum markers .Scand JGastroenterol 2005, 40 (7):867-872.
  34. Fontana RJ, Kleiner DE, Bilonick R, Terrault N, Afdhal N, Belle SH, Jeffers LJ, Ramcharran D, Ghany MG, Hoofnagle JH et al:Modeling hepatic fibrosis in African American and Caucasian American patients with chronic hepatitis Cvirus infection .Hepatology 2006, 44 (4):925-935.
  35. Koda M, Matunaga Y, Kawakami M, Kishimoto Y, Suou T, Murawaki Y: FibroIndex, a practical index for predicting significant fibrosis in patients with chronic hepatitis C.Hepatology 2007, 45 (2):297-306.
  36. Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J,M SS, Torriani FJ, Dieterich DT, Thomas DL et al: Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection .Hepatology 2006, 43 (6):1317-1325.
  37. Leroy V, Monier F, Bottari S, Trocme C, Sturm N, Hilleret MN, Morel F, Zarski JP: Circulating matrix metalloproteinases 1, 2, 9and their inhibitors TIMP-1 and TIMP-2 as serum markers of liver fibrosis in patients with chronic hepatitis C: comparison with PIIINP and hyaluronic acid .Am JGastroenterol 2004, 99 (2):271-279.
  38. Fontana RJ, Goodman ZD, Dienstag JL, Bonkovsky HL, Naishadham D, Sterling RK, Su GL, Ghosh M, Wright EC, Group H-CT: Relationship of serum fibrosis markers with liver fibrosis stage and collagen content in patients with advanced chronic hepatitis C.Hepatology 2008, 47 (3):789-798.
  39. Shiha G, Seif S,Eldesoky A, Elbasiony M, Soliman R, Metwally A, Zalata K, Mikhail N: Asimple bedside blood test (Fibrofast; FIB-5) issuperior to FIB-4 index for the differentiation between non-significant and significant fibrosis in patients with chronic hepatitis C.Hepatol Int 2017, 11 (3):286-291.
  40. Hui AY, Chan HL, Wong VW, Liew CT, Chim AM, Chan FK, Sung JJ: Identification of chronic hepatitis Bpatients without significant liver fibrosis by a simple noninvasive predictive model .Am JGastroenterol 2005, 100 (3):616-623.
  41. Zeng MD, Lu LG, Mao YM, Qiu DK, Li JQ, Wan MB, Chen CW, Wang JY, Cai X, Gao CF et al:Prediction of significant fibrosis in HBeAg-positive patients with chronic hepatitis B by anoninvasive model .Hepatology 2005, 42 (6):1437-1445.
  42. Cao Z, Li Z, Wang H, Liu Y,Xu Y,Mo R, Ren P,Chen L, Lu J,Li Het al:Algorithm of Golgi protein 73 and liver stiffness accurately diagnoses significant fibrosis in chronic HBV infection . Liver Int 2017, 37 (11):1612-1621.
  43. Bracht T, Molleken C, Ahrens M, Poschmann G, Schlosser A, Eisenacher M, Stuhler K, Meyer HE, Schmiegel WH, Holmskov U et al:Evaluation of the biomarker candidate MFAP4 for non-invasive assessment of hepatic fibrosis in hepatitis Cpatients .JTransl Med 2016, 14 (1):201.
  44. Shirabe K, Bekki Y, Gantumur D, Araki K, Ishii N, Kuno A, Narimatsu H, Mizokami M: Mac-2 binding protein glycan isomer (M2BPGi) is anew serum biomarker for assessing liver fibrosis: more than abiomarker of liver fibrosis .JGastroenterol 2018, 53 (7):819-826.
  45. Zou X, Zhu MY, Yu DM, Li W, Zhang DH, Lu FJ, Gong QM, Liu F,Jiang JH, Zheng MH et al:Serum WFA(+) -M2BP levels for evaluation of early stages of liver fibrosis in patients with chronic hepatitis Bvirus infection . Liver Int 2017, 37 (1):35-44.
  46. Varchetta S,Mele D, Lombardi A, Oliviero B, Mantovani S,Tinelli C,Spreafico M, Prati D, Ludovisi S,Ferraioli Get al: Lack of Siglec-7 expression identifies a dysfunctional natural killer cell subset associated with liver inflammation and fibrosis in chronic HCV infection .Gut 2016, 65 (12):1998-2006.
  47. Staufer K, Dengler M, Huber H, Marculescu R, Stauber R, Lackner C, Dienes HP, Kivaranovic D, Schachner C, Zeitlinger M et al:The non-invasive serum biomarker soluble Axl accurately detects advanced liver fibrosis and cirrhosis .Cell Death Dis 2017, 8(10):e3135.
  48. Pereira TA, Syn WK, Pereira FE, Lambertucci JR, Secor WE, Diehl AM: Serum osteopontin is abiomarker of severe fibrosis and portal hypertension in human and murine schistosomiasis mansoni .Int JParasitol 2016, 46 (13-14):829-832.
  49. Vagu C, Sultana C,Ruta S:Serum iron markers in patients with chronic hepatitis Cinfection .Hepat Mon 2013, 13 (10):e13136.
  50. Miranda AS, Simoes ESAC: Serum levels of angiotensin converting enzyme as abiomarker of liver fibrosis . World JGastroenterol 2017, 23 (48):8439-8442.
  51. Poynard T,de Ledinghen V,Zarski JP, Stanciu C, Munteanu M, Vergniol J,France J,Trifan A, Moussalli J,Lebray Pet al:FibroTest and Fibroscan performances revisited in patients with chronic hepatitis C. Impact of the spectrum effect and the applicability rate .Clin Res Hepatol Gastroenterol 2011, 35 (11):720-730.
  52. Poynard T,Munteanu M, Deckmyn O, Ngo Y,Drane F,Messous D, Castille JM, Housset C, Ratziu V,Imbert-Bismut F: Applicability and precautions of use of liver injury biomarker FibroTest. Areappraisal at 7years of age . BMC Gastroenterol 2011, 11 :39.
  53. Leroy V,Halfon P,Bacq Y,Boursier J,Rousselet MC, Bourliere M, de Muret A, Sturm N, Hunault G, Penaranda Get al: Diagnostic accuracy, reproducibility and robustness of fibrosis blood tests in chronic hepatitis C: a meta-analysis with individual data .Clin Biochem 2008, 41 (16-17):1368-1376.
  54. Cales P,Veillon P,Konate A, Mathieu E, Ternisien C, Chevailler A, Godon A, Gallois Y,Joubaud F,Hubert-Fouchard I et al:Reproducibility of blood tests of liver fibrosis in clinical practice .Clin Biochem 2008, 41 (1-2):10-18.
  55. Sebastiani G, Ghali P, Wong P, Klein MB, Deschenes M, Myers RP: Physicians' practices for diagnosing liver fibrosis in chronic liver diseases: a nationwide, Canadian survey .Can JGastroenterol Hepatol 2014, 28 (1):23-30.
  56. Park G, Katelaris P,Jones DB, Ngu M, Le Couteur D: Caution before embracing serum markers of liver fibrosis in clinical practice .Gastroenterology 2005, 128 (4):1145-1146; author reply 1146.
  57. Poynard T,Munteanu M, Imbert-Bismut F,Charlotte F,Thabut D, Le Calvez S,Messous D, Thibault V,Benhamou Y, Moussalli Jet al:Prospective analysis of discordant results between biochemical markers and biopsy in patients with chronic hepatitis C.Clin Chem 2004, 50 (8):1344-1355.
  58. Sandrin L, Fourquet B, Hasquenoph JM, Yon S, Fournier C, Mal F,Christidis C, Ziol M, Poulet B, Kazemi Fet al: Transient elastography: anew noninvasive method for assessment of hepatic fibrosis .Ultrasound Med Biol 2003, 29 (12):1705-1713.
  59. Castera L, Vergniol J,Foucher J,Le Bail B, Chanteloup E, Haaser M, Darriet M, Couzigou P, De Ledinghen V: Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C.Gastroenterology 2005, 128 (2):343-350.
  60. Colombo S,Belloli L,Zaccanelli M, Badia E, Jamoletti C,Buonocore M, Del Poggio P: Normal liver stiffness and its determinants in healthy blood donors .Dig Liver Dis 2011, 43 (3):231-236.
  61. Kim SU, Choi GH, Han WK, Kim BK, Park JY, Kim DY, Choi JS, Yang SC, Choi EH, Ahn SH et al:What are 'true normal' liver stiffness values using FibroScan?: aprospective study in healthy living liver and kidney donors in South Korea .Liver Int 2010, 30 (2):268-274.
  62. Tsai E, Lee TP: Diagnosis and Evaluation of Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis, Including Noninvasive Biomarkers and Transient Elastography .Clin Liver Dis 2018, 22 (1):73-92.
  63. Della-Guardia B, Evangelista AS, Felga GE, Marins LV, Salvalaggio PR, Almeida MD: Diagnostic Accuracy of Transient Elastography for Detecting Liver Fibrosis After Liver Trannsplantation: ASpecific Cut-Off Value Is Really Needed? Dig Dis Sci 2017, 62 (1):264-272.
  64. Lucidarme D, Foucher J,Le Bail B, Vergniol J,Castera L,Duburque C,Forzy G, Filoche B, Couzigou P,de Ledinghen V: Factors of accuracy of transient elastography (fibroscan) for the diagnosis of liver fibrosis in chronic hepatitis C.Hepatology 2009, 49 (4):1083-1089.
  65. Juarez-Hernandez E, Uribe-Ramos MH, Ramos-Ostos MH, Lopez-Ramirez AY, Ornelas-Arroyo S,Romero-Flores JL, Mendez-Sanchez N, Uribe M, Chavez-Tapia NC: Factors Associated with the Quality of Transient Elastography . Dig Dis Sci 2015, 60 (7):2177-2182.
  66. Fraquelli M, Rigamonti C, Casazza G, Conte D, Donato MF, Ronchi G, Colombo M: Reproducibility of transient
  67. Perazzo H, Fernandes FF, Gomes A, Terra C, Perez RM, Figueiredo FA: Interobserver variability in transient elastography analysis of patients with chronic hepatitis C.Liver Int 2015, 35 (5):1533-1539.
  68. Carrion JA, Puigvehi M, Coll S,Garcia-Retortillo M, Canete N, Fernandez R, Marquez C, Gimenez MD, Garcia M, Bory Fet al:Applicability and accuracy improvement of transient elastography using the M and XL probes by experienced operators .JViral Hepat 2015, 22 (3):297-306.
  69. Castera L, Foucher J,Bernard PH, Carvalho F,Allaix D, Merrouche W, Couzigou P,de Ledinghen V: Pitfalls of liver stiffness measurement: a 5-year prospective study of 13,369 examinations . Hepatology 2010, 51 (3):828-835.
  70. Myers RP, Pomier-Layrargues G, Kirsch R, Pollett A, Duarte-Rojo A, Wong D, Beaton M, Levstik M, Crotty P, Elkashab M: Feasibility and diagnostic performance of the FibroScan XL probe for liver stiffness measurement in overweight and obese patients .Hepatology 2012, 55 (1):199-208.
  71. Puigvehi M, Broquetas T, Coll S, Garcia-Retortillo M, Canete N, Fernandez R, Gimeno J, Sanchez J, Bory F, Pedro-Botet Jet al:Impact of anthropometric features on the applicability and accuracy of FibroScan((R)) (M and XL) in overweight/obese patients .JGastroenterol Hepatol 2017, 32 (10):1746-1753.
  72. Friedrich-Rust M, Zeuzem S: Reproducibility and limitations of transient elastography .Liver Int 2009, 29 (5):619-620.
  73. Castera L,Pinzani M: Biopsy and non-invasive methods for the diagnosis of liver fibrosis: does ittake two to tango? Gut 2010, 59 (7):861-866.
  74. Wong VW, Vergniol J,Wong GL, Foucher J,Chan HL, Le Bail B, Choi PC, Kowo M, Chan AW, Merrouche W et al: Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease . Hepatology 2010, 51 (2):454-462.
  75. Macaluso FS, Maida M, Camma C,Cabibbo G, Cabibi D, Alduino R, Di Marco V,Craxi A, Petta S:Steatosis affects the performance of liver stiffness measurement for fibrosis assessment in patients with genotype 1chronic hepatitis C.JHepatol 2014, 61 (3):523-529.
  76. Yoshioka K, Hashimoto S,Kawabe N: Measurement of liver stiffness as anon-invasive method for diagnosis of non-alcoholic fatty liver disease .Hepatol Res 2015, 45 (2):142-151.
  77. Joo SK, Kim W, Kim D, Kim JH, Oh S,Lee KL, Chang MS, Jung YJ, So YH, Lee MS et al:Steatosis severity affects the diagnostic performances of noninvasive fibrosis tests in nonalcoholic fatty liver disease .Liver Int 2018, 38 (2):331-341.
  78. Berzigotti A, Castera L: Update on ultrasound imaging of liver fibrosis .JHepatol 2013, 59 (1):180-182.
  79. Tan CH, Venkatesh SK: Magnetic Resonance Elastography and Other Magnetic Resonance Imaging Techniques in Chronic Liver Disease: Current Status and Future Directions .Gut Liver 2016, 10 (5):672-686.
  80. Nightingale K, Soo MS, Nightingale R, Trahey G: Acoustic radiation force impulse imaging: in vivo demonstration of clinical feasibility .Ultrasound Med Biol 2002, 28 (2):227-235.
  81. Berna-Serna JD, Sanchez-Jimenez R, Velazquez-Marin F, Sainz de Baranda P, Guzman-Aroca F, Fernandez-Hernandez C, Domenech-Abellan E, Abellan-Rivero D, Ruiz-Merino G, Madrid-Conesa Jet al:Acoustic radiation force impulse imaging for detection of liver fibrosis in overweight and obese children .Acta Radiol 2018, 59 (2):247-253.
  82. Muller M, Gennisson JL, Deffieux T, Tanter M, Fink M: Quantitative viscoelasticity mapping of human liver using supersonic shear imaging: preliminary in vivo feasibility study .Ultrasound Med Biol 2009, 35 (2):219-229.
  83. Beland MD, Brown SF, Machan JT, Taliano RJ, Promrat K, Cronan JJ: Apilot study estimating liver fibrosis with
  84. Deffieux T,Gennisson JL, Bousquet L,Corouge M, Cosconea S,Amroun D, Tripon S,Terris B, Mallet V,Sogni Pet al: Investigating liver stiffness and viscosity for fibrosis, steatosis and activity staging using shear wave elastography .JHepatol 2015, 62 (2):317-324.
  85. Muthupillai R, Lomas DJ, Rossman PJ, Greenleaf JF, Manduca A, Ehman RL: Magnetic resonance elastography by direct visualization of propagating acoustic strain waves .Science 1995, 269 (5232):1854-1857.
  86. Talwalkar JA, Yin M, Fidler JL, Sanderson SO, Kamath PS, Ehman RL: Magnetic resonance imaging of hepatic fibrosis: emerging clinical applications .Hepatology 2008, 47 (1):332-342.
  87. Huwart L, Sempoux C, Vicaut E, Salameh N, Annet L, Danse E, Peeters F, ter Beek LC, Rahier J,Sinkus Ret al: Magnetic resonance elastography for the noninvasive staging of liver fibrosis .Gastroenterology 2008, 135 (1):32-40.
  88. Asbach P,Klatt D, Schlosser B, Biermer M, Muche M, Rieger A, Loddenkemper C, Somasundaram R, Berg T,Hamm Bet al:Viscoelasticity-based staging of hepatic fibrosis with multifrequency MR elastography .Radiology 2010, 257 (1):80-86.
  89. Carrion JA, Navasa M, Forns X: MR elastography to assess liver fibrosis .Radiology 2008, 247 (2):591; author reply 591-592.
  90. Venkatesh SK, Yin M, Ehman RL: Magnetic resonance elastography of liver: technique, analysis, and clinical applications .JMagn Reson Imaging 2013, 37 (3):544-555.
  91. Huber A, Ebner L, Montani M, Semmo N, Roy Choudhury K, Heverhagen J,Christe A: Computed tomography findings in liver fibrosis and cirrhosis .Swiss Med Wkly 2014, 144 :w13923.
  92. Liu P, Li P, He W, Zhao LQ: Liver and spleen volume variations in patients with hepatic fibrosis .World J Gastroenterol 2009, 15 (26):3298-3302.
  93. Goshima S,Kanematsu M, Watanabe H, Kondo H, Kawada H, Moriyama N, Bae KT: Gd-EOB-DTPA-enhanced MR imaging: prediction of hepatic fibrosis stages using liver contrast enhancement index and liver-to-spleen volumetric ratio .JMagn Reson Imaging 2012, 36 (5):1148-1153.
  94. Ronot M, Asselah T, Paradis V, Michoux N, Dorvillius M, Baron G, Marcellin P, Van Beers BE, Vilgrain V: Liver fibrosis in chronic hepatitis Cvirus infection: differentiating minimal from intermediate fibrosis with perfusion CT .Radiology 2010, 256 (1):135-142.
  95. Motosugi U, Ichikawa T,Sou H, Morisaka H, Sano K, Araki T: Multi-organ perfusion CT in the abdomen using a 320-detector row CT scanner: preliminary results of perfusion changes in the liver, spleen, and pancreas of cirrhotic patients .Eur JRadiol 2012, 81 (10):2533-2537.
  96. Wang JC, Fu R, Tao XW, Mao YF, Wang F,Zhang ZC, Yu WW, Chen J,He J,Sun BC: Aradiomics-based model on non-contrast CT for predicting cirrhosis: make the most of image data .Biomark Res 2020, 8:47.
  97. Wang J,Tang S, Mao Y,Wu J,Xu S, Yue Q, Chen J,He J,Yin Y: Radiomics analysis of contrast-enhanced CT for staging liver fibrosis: an update for image biomarker .Hepatol Int 2022, 16 (3):627-639.
  98. Chou R, Wasson N: Blood tests to diagnose fibrosis or cirrhosis in patients with chronic hepatitis Cvirus infection: asystematic review .Ann Intern Med 2013, 158 (11):807-820.
  99. Salkic NN, Jovanovic P,Hauser G, Brcic M: FibroTest/Fibrosure for significant liver fibrosis and cirrhosis in chronic hepatitis B: ameta-analysis .Am JGastroenterol 2014, 109 (6):796-809.
  100. Lin ZH, Xin YN, Dong QJ, Wang Q, Jiang XJ, Zhan SH, Sun Y, Xuan SY: Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis .Hepatology 2011, 53 (3):726-736.
  101. Xiao G, Yang J,Yan L: Comparison of diagnostic accuracy of aspartate aminotransferase to platelet ratio
  102. Tanwar S, Trembling PM, Hogan BJ, Parkes J,Harris S, Grant P, Nastouli E, Ocker M, Wehr K, Herold Cet al: Biomarkers of Hepatic Fibrosis in Chronic Hepatitis C: AComparison of 10 Biomarkers Using 2Different Assays for Hyaluronic Acid .JClin Gastroenterol 2017, 51 (3):268-277.
  103. Lupsor M, Badea R, Stefanescu H, Grigorescu M, Sparchez Z, Serban A, Branda H, Iancu S, Maniu A: Analysis of histopathological changes that influence liver stiffness in chronic hepatitis C. Results from acohort of 324 patients .JGastrointestin Liver Dis 2008, 17 (2):155-163.
  104. Kirk GD, Astemborski J,Mehta SH, Spoler C, Fisher C, Allen D, Higgins Y,Moore RD, Afdhal N, Torbenson M et al: Assessment of liver fibrosis by transient elastography in persons with hepatitis C virus infection or HIV-hepatitis Cvirus coinfection .Clin Infect Dis 2009, 48 (7):963-972.
  105. Degos F, Perez P, Roche B, Mahmoudi A, Asselineau J,Voitot H, Bedossa P, group Fs: Diagnostic accuracy of FibroScan and comparison to liver fibrosis biomarkers in chronic viral hepatitis: a multicenter prospective study (the FIBROSTIC study) .JHepatol 2010, 53 (6):1013-1021.
  106. Cardoso AC, Carvalho-Filho RJ, Stern C, Dipumpo A, Giuily N, Ripault MP, Asselah T,Boyer N, Lada O, Castelnau Cet al:Direct comparison of diagnostic performance of transient elastography in patients with chronic hepatitis Band chronic hepatitis C.Liver Int 2012, 32 (4):612-621.
  107. Zarski JP, Sturm N, Guechot J,Paris A, Zafrani ES, Asselah T,Boisson RC, Bosson JL, Guyader D, Renversez JC et al: Comparison of nine blood tests and transient elastography for liver fibrosis in chronic hepatitis C: the ANRS HCEP-23 study .JHepatol 2012, 56 (1):55-62.
  108. Seo YS, Kim MY, Kim SU, Hyun BS, Jang JY, Lee JW, Lee JI, Suh SJ, Park SY, Park H et al:Accuracy of transient elastography in assessing liver fibrosis in chronic viral hepatitis: Amulticentre, retrospective study .Liver Int 2015, 35 (10):2246-2255.
  109. Elsharkawy A, Alboraie M, Fouad R, Asem N, Abdo M, Elmakhzangy H, Mehrez M, Khattab H, Esmat G: Establishing ultrasound based transient elastography cutoffs for different stages of hepatic fibrosis and cirrhosis in Egyptian chronic hepatitis Cpatients .Arab JGastroenterol 2017, 18 (4):210-215.
  110. Foucher J,Chanteloup E, Vergniol J,Castera L, Le Bail B, Adhoute X, Bertet J,Couzigou P, de Ledinghen V: Diagnosis of cirrhosis by transient elastography (FibroScan): aprospective study .Gut 2006, 55 (3):403-408.
  111. Coco B, Oliveri F,Maina AM, Ciccorossi P,Sacco R, Colombatto P,Bonino F,Brunetto MR: Transient elastography: anew surrogate marker of liver fibrosis influenced by major changes of transaminases .JViral Hepat 2007, 14 (5):360-369.
  112. Oliveri F,Coco B, Ciccorossi P,Colombatto P,Romagnoli V,Cherubini B, Bonino F,Brunetto MR: Liver stiffness in the hepatitis B virus carrier: a non-invasive marker of liver disease influenced by the pattern of transaminases .World JGastroenterol 2008, 14 (40):6154-6162.
  113. Goyal R, Mallick SR, Mahanta M, Kedia S, Shalimar, Dhingra R, Sharma H, Das P, Datta Gupta S, Panda Set al: Fibroscan can avoid liver biopsy in Indian patients with chronic hepatitis B.JGastroenterol Hepatol 2013, 28 (11):1738-1745.
  114. Zeng J,Zheng J,Huang Z, Chen S,Liu J,Wu T,Zheng R, Lu M: Comparison of 2-D Shear Wave Elastography and Transient Elastography for Assessing Liver Fibrosis in Chronic Hepatitis B.Ultrasound Med Biol 2017, 43 (8):1563-1570.
  115. Friedrich-Rust M, Ong MF, Martens S, Sarrazin C, Bojunga J,Zeuzem S, Herrmann E: Performance of transient elastography for the staging of liver fibrosis: ameta-analysis .Gastroenterology 2008, 134 (4):960-974.
  116. Tsochatzis EA, Gurusamy KS, Ntaoula S, Cholongitas E, Davidson BR, Burroughs AK: Elastography for the diagnosis of severity of fibrosis in chronic liver disease: ameta-analysis of diagnostic accuracy .JHepatol
  117. Stebbing J,Farouk L, Panos G, Anderson M, Jiao LR, Mandalia S,Bower M, Gazzard B, Nelson M: Ameta-analysis of transient elastography for the detection of hepatic fibrosis .JClin Gastroenterol 2010, 44 (3):214-219.
  118. Geng XX, Huang RG, Lin JM, Jiang N, Yang XX: Transient elastography in clinical detection of liver cirrhosis: A systematic review and meta-analysis .Saudi JGastroenterol 2016, 22 (4):294-303.
  119. Cassinotto C, Lapuyade B, Mouries A, Hiriart JB, Vergniol J,Gaye D, Castain C, Le Bail B, Chermak F,Foucher Jet al: Non-invasive assessment of liver fibrosis with impulse elastography: comparison of Supersonic Shear Imaging with ARFI and FibroScan(R) .JHepatol 2014, 61 (3):550-557.
  120. Wu T,Wang P,Zhang T, Zheng J,Li S, Zeng J,Kudo M, Zheng R: Comparison of Two-Dimensional Shear Wave Elastography and Real-Time Tissue Elastography for Assessing Liver Fibrosis in Chronic Hepatitis B.Dig Dis 2016, 34 (6):640-649.
  121. Friedrich-Rust M, Nierhoff J,Lupsor M, Sporea I,Fierbinteanu-Braticevici C, Strobel D, Takahashi H, Yoneda M, Suda T, Zeuzem Set al:Performance of Acoustic Radiation Force Impulse imaging for the staging of liver fibrosis: apooled meta-analysis .JViral Hepat 2012, 19 (2):e212-219.
  122. Hu X, Qiu L,Liu D, Qian L: Acoustic Radiation Force Impulse (ARFI) Elastography for noninvasive evaluation of hepatic fibrosis in chronic hepatitis B and C patients: asystematic review and meta-analysis .Med Ultrason 2017, 19 (1):23-31.
  123. Herrmann E, de Ledinghen V,Cassinotto C,Chu WC, Leung VY, Ferraioli G, Filice C,Castera L,Vilgrain V,Ronot M et al:Assessment of biopsy-proven liver fibrosis by two-dimensional shear wave elastography: An individual patient data-based meta-analysis .Hepatology 2018, 67 (1):260-272.
  124. Bota S, Sporea I,Sirli R, Popescu A, Gradinaru-Tascau O: How useful are ARFI elastography cut-off values proposed by meta-analysis for predicting the significant fibrosis and compensated liver cirrhosis? Med Ultrason 2015, 17 (2):200-205.
  125. Zhang D, Chen M, Wang R, Liu Y, Zhang D, Liu L, Zhou G: Comparison of acoustic radiation force impulse imaging and transient elastography for non-invasive assessment of liver fibrosis in patients with chronic hepatitis B.Ultrasound Med Biol 2015, 41 (1):7-14.
  126. Venkatesh SK, Wang G, Lim SG, Wee A: Magnetic resonance elastography for the detection and staging of liver fibrosis in chronic hepatitis B.Eur Radiol 2014, 24 (1):70-78.
  127. Ichikawa S, Motosugi U, Morisaka H, Sano K, Ichikawa T, Tatsumi A, Enomoto N, Matsuda M, Fujii H, Onishi H: Comparison of the diagnostic accuracies of magnetic resonance elastography and transient elastography for hepatic fibrosis .Magn Reson Imaging 2015, 33 (1):26-30.
  128. Shi Y,Xia F,Li QJ, Li JH, Yu B, Li Y,An H, Glaser KJ, Tao S,Ehman RL et al:Magnetic Resonance Elastography for the Evaluation of Liver Fibrosis in Chronic Hepatitis Band Cby Using Both Gradient-Recalled Echo and Spin-Echo Echo Planar Imaging: AProspective Study .Am JGastroenterol 2016, 111 (6):823-833.
  129. Hennedige TP, Wang G, Leung FP, Alsaif HS, Teo LL, Lim SG, Wee A, Venkatesh SK: Magnetic Resonance Elastography and Diffusion Weighted Imaging in the Evaluation of Hepatic Fibrosis in Chronic Hepatitis B. Gut Liver 2017, 11 (3):401-408.
  130. Su LN, Guo SL, Li BX, Yang P: Diagnostic value of magnetic resonance elastography for detecting and staging of hepatic fibrosis: ameta-analysis .Clin Radiol 2014, 69 (12):e545-552.
  131. Singh S, Venkatesh SK, Wang Z, Miller FH, Motosugi U, Low RN, Hassanein T,Asbach P,Godfrey EM, Yin M et al: Diagnostic performance of magnetic resonance elastography in staging liver fibrosis: asystematic review and meta-analysis of individual participant data .Clin Gastroenterol Hepatol 2015, 13 (3):440-451 e446.
  132. Bohte AE, de Niet A, Jansen L, Bipat S,Nederveen AJ, Verheij J,Terpstra V,Sinkus R, van Nieuwkerk KM, de Knegt RJ et al:Non-invasive evaluation of liver fibrosis: acomparison of ultrasound-based transient elastography
  133. Guo Y, Parthasarathy S, Goyal P, McCarthy RJ, Larson AC, Miller FH: Magnetic resonance elastography and acoustic radiation force impulse for staging hepatic fibrosis: a meta-analysis .Abdom Imaging 2015, 40 (4):818-834.
  134. Yasaka K, Akai H, Kunimatsu A, Abe O, Kiryu S:Deep learning for staging liver fibrosis on CT: apilot study .Eur Radiol 2018, 28 (11):4578-4585.
  135. Schuppan D, Pinzani M: Anti-fibrotic therapy: lost in translation? JHepatol 2012, 56 Suppl 1:S66-74.
  136. Deng R, Cui X, Dong Y,Tang Y,Tao X, Wang S,Wang J,Chen L: Construction of circRNA-Based ceRNA Network to Reveal the Role of circRNAs in the Progression and Prognosis of Hepatocellular Carcinoma .Front Genet 2021, 12 :626764.
  137. Trepo E, Potthoff A, Pradat P,Bakshi R, Young B, Lagier R, Moreno C, Verset L, Cross R, Degre Det al:Role of a cirrhosis risk score for the early prediction of fibrosis progression in hepatitis Cpatients with minimal liver disease .JHepatol 2011, 55 (1):38-44.
  138. Huang L,Liu J,Zhang XO, Sibley K, Najjar SM, Lee MM, Wu Q: Inhibition of protein arginine methyltransferase 5enhances hepatic mitochondrial biogenesis .JBiol Chem 2018, 293 (28):10884-10894.
  139. JiD, Chen GF, Wang JC, Cao LH, Lu F,Mu XX, Zhang XY, Lu XJ: Identification of TAF1, HNF4A, and CALM2 as potential therapeutic target genes for liver fibrosis .JCell Physiol 2019, 234 (6):9045-9051.
  140. Ji D, Chen GF, Wang JC, Ji SH, Wu XW, Lu XJ, Chen JL, Li JT: Hsa_circ_0070963 inhibits liver fibrosis via regulation of miR-223-3p and LEMD3 .Aging (Albany NY) 2020, 12 (2):1643-1655.
  141. Cheung KJ, Libbrecht L, Tilleman K, Deforce D, Colle I, Van Vlierberghe H: Galectin-3-binding protein: a serological and histological assessment in accordance with hepatitis C-related liver fibrosis .Eur J Gastroenterol Hepatol 2010, 22 (9):1066-1073.
  142. Lu Y, Liu J,Lin C, Wang H, Jiang Y, Wang J,Yang P, He F: Peroxiredoxin 2: apotential biomarker for early diagnosis of hepatitis B virus related liver fibrosis identified by proteomic analysis of the plasma .BMC Gastroenterol 2010, 10 :115.
  143. Hannivoort RA, Hernandez-Gea V, Friedman SL: Genomics and proteomics in liver fibrosis and cirrhosis . Fibrogenesis Tissue Repair 2012, 5(1):1.
  144. Szabo G, Bala S:MicroRNAs in liver disease .Nat Rev Gastroenterol Hepatol 2013, 10 (9):542-552.
  145. Hyun J,Jung Y: MicroRNAs in liver fibrosis: Focusing on the interaction with hedgehog signaling .World J Gastroenterol 2016, 22 (29):6652-6662.
  146. Jin BX, Zhang YH, Jin WJ, Sun XY, Qiao GF, Wei YY, Sun LB, Zhang WH, Li N: MicroRNA panels as disease biomarkers distinguishing hepatitis B virus infection caused hepatitis and liver cirrhosis .Sci Rep 2015, 5:15026.
  147. Omran D, Zayed RA, Nabeel MM, Mobarak L, Zakaria Z, Farid A, Hassany M, Saif S, Mostafa M, Saad OK et al: Evaluating Diagnostic Accuracy of Noninvasive Tests in Assessment of Significant Liver Fibrosis in Chronic Hepatitis CEgyptian Patients .Viral Immunol 2018, 31 (4):315-320.
  148. Sebastiani G, Vario A, Guido M, Noventa F, Plebani M, Pistis R, Ferrari A, Alberti A: Stepwise combination algorithms of non-invasive markers to diagnose significant fibrosis in chronic hepatitis C.JHepatol 2006, 44 (4):686-693.
  149. Sebastiani G, Halfon P,Castera L, Pol S, Thomas DL, Mangia A, Di Marco V, Pirisi M, Voiculescu M, Guido M et al: SAFE biopsy: avalidated method for large-scale staging of liver fibrosis in chronic hepatitis C.Hepatology 2009, 49 (6):1821-1827.
  150. Boursier J,Vergniol J,Sawadogo A, Dakka T,Michalak S,Gallois Y,Le Tallec V,Oberti F,Fouchard-Hubert I,Dib Net al:The combination of ablood test and Fibroscan improves the non-invasive diagnosis of liver fibrosis .
  151. Boursier J,de Ledinghen V, Zarski JP, Rousselet MC, Sturm N, Foucher J,Leroy V, Fouchard-Hubert I,Bertrais S, Gallois Yet al:Anew combination of blood test and fibroscan for accurate non-invasive diagnosis of liver fibrosis stages in chronic hepatitis C.Am JGastroenterol 2011, 106 (7):1255-1263.
  152. Yasaka K, Akai H, Kunimatsu A, Abe O, Kiryu S: Liver Fibrosis: Deep Convolutional Neural Network for Staging by Using Gadoxetic Acid-enhanced Hepatobiliary Phase MR Images .Radiology 2018, 287 (1):146-155.
  153. Wang J,Zhang X, Liu J,Yin Y: Editorial: The use of data mining in radiological-pathological images for personal medicine .Front Genet 2023, 14 :1187040.
  154. Li Y, Li T, Zhai D, Xie C, Kuang X, Lin Y, Shao N: Quantification of ferroptosis pathway status revealed heterogeneity in breast cancer patients with distinct immune microenvironment .Front Oncol 2022, 12 :956999.
  155. Xing XL, Liu Y, Liu JH, Zhou HF, Zhang HR, Zuo Q, Bu P, Duan T, Zhou Y, Xiao ZQ: A nomogram integrating ferroptosis-and immune-related biomarker for prediction of prognosis and diagnosis in kidney renal clear cell carcinoma .Eur Rev Med Pharmacol Sci 2022, 26 (17):6176-6186.