Lviv clinical bulletin 2020, 3(31): 62-72

Modern Principles of Liver Fibrosis Diagnosis in Patients With Chronic Diffuse Liver Lesions: Literature Review and Clinical Case Description

Y. Leshchuk, O. Abrahamovych, M. Abrahamovych

Danylo Halytsky Lviv National Medical University

Introduction. Chronic diffuse liver lesions, which is at a certain stage and phase of the disease characterized by excessive accumulation of components of the extracellular matrix, namely fibrosis, – are a heterogeneous multi etiological group of diseases that are characterized by the high prevalence, subclinical course in the initial stages, low curability and reversibility of the pathological process in the late stages, and therefore cause considerable clinical, epidemiological and socio-economic problem of our time.

The main way of progression of chronic diffuse liver lesions, regardless of the etiological factor that led to its damage – is the process of fibrogenesis. Quantitative indicators of the severity and rate of fibrosis progression are the most important clinical parameter, the determination of which is crucial for choosing the right treatment and for monitoring its effectiveness. Today, there is no universal method and only a combination of different laboratory and instrumental methods of examination can significantly increase their diagnostic value for early detection of liver fibrosis in the case of chronic diffuse liver diseases. However, the range of possibilities of certain diagnostic methods is constantly expanding and recently the elastographic method has become increasingly important.

The aim of the study. To make the literature review concerning the modern principles of liver fibrosis diagnosis in patients with chronic diffuse liver lesions, to describe the clinical case.

Materials and methods. The content analysis, method of the system and comparative analysis, the bibliosemantic method of study of the actual scientific studies concerning modern principles of diagnosis of patients with diffuse liver disease, a clinical case is described.

Results. The literature review demonstrates the importance and relevance of early and comprehensive diagnosis of chronic diffuse liver disease. Hepatic fibrosis is the basis for portal hypertension, varicose veins, ascites and liver failure. Decompensated cirrhosis is associated with high mortality and the only effective treatment is liver transplantation.

Assessment of the degree of liver fibrosis is important for several reasons: to determine the prognosis of chronic liver damage, to select patients for specific (etiotropic) treatment and possible liver transplantation. Therefore, the problem of diagnosis and detection of early initial stages of liver fibrosis for the timely appointment of therapeutic agents, which are aimed at reducing the rate of its progression and prevent cirrhosis and liver cancer, is extremely important for modern medicine. It is known that the “gold standard” for the diagnosis of liver fibrosis is a liver biopsy, but the method has many limitations and contraindications.

Elastography is one of the most promising non-invasive methods to diagnose liver fibrosis and steatosis in the case of chronic diffuse liver lesions, which can be used as an alternative to biopsy. Given its widespread implementation in clinical practice, groups of scientists from around the world are paying more and more attention to the study of factors that may affect the results of elastometry and its diagnostic effectiveness.

The advantages of the method of liver elastography include: non-invasive, no contraindications, simplicity, fast execution and interpretation; the ability to determine the stage of fibrosis in patients who can not perform a liver biopsy (coagulopathy, thrombocytopenia); the possibility of repeated procedures to assess the increase in severity.

Conclusions. Thanks to modern scientific achievements, the latest technologies have been introduced into clinical practice, with the help of which clinicians successfully improve the diagnosis of chronic diffuse liver diseases, in particular, through the use of quantitative detection of fibrotic changes in it, establishing the nature of abdominal fluid (serous or mucinous), assessment of hepatic venous pressure due to safe non-invasive and informative method of shear wave elastography of the liver, a method that not only allows to objectify the verification of the diagnosis, but also to dynamically assess the efficiency of treatment.


  1. Abrahamovych MO, Abrahamovych OO. Classification of liver cirrhosis: a retrospective view of the problem and its modern solution taking into account the syntropic co- and polymorbid lesions of the patient. Medicine of Ukrainian Transport. 2013;2:10-16. (Ukrainian)
  2. Abrahamovych MO, Farmaha ML. Treatment of the Liver Cirrhosis: Modern Principles, Considering Syntropic Co- and Multimorbid Lesions of other Organs and Systems of Organs. Lviv Clinical Bulletin. 2013;2:37-45. (Ukrainian)
  3. Abrahamovych OO, Abrahamovych MO, Farmaha ML, Tolopko SY. Characteristics of syntropic polymorbid lesions in patients with liver cirrhosis and the dependence of their frequency on the severity of the disease. Contemporary Gastroenterology. 2013;4:23-30. (Ukrainian)
  4. Borsukov AV. Adaptation of the World and European Recommendations on Liver Elastography for Domestic Radiology. Medical Visualization. 2017;(6):63-71. (Russian)
  5. Dynnik OB, Zhaivoronok MM, Kobilyak NN, Kharchenko MS. Ultrasound elastography: theory and practice of creating a training simulator. Radiation Diagnostics, Radiation Therapy. 2014;3:42-53. (Ukrainian)
  6. Dynnik OB, Lynskaia AV, Kobilyak NN. Shearwave elastography and elastometry of the liver parenchyma (methodological aspects). Radiation Diagnostics, Radiation Therapy. 2014;1-2:73-82. (Russian)
  7. Zhuravlyova LV, Ogneva OV. The use of elastography in patients with chronic liver diseases. Gastroenterology. 2018;52(2):98-103. (Russian)
  8. Sirchak ES, Petrichko OІ, Ivachevskij MM, Arhij EJ, Rusin VI. Noninvasive methods of diagnostics of liver fibrosis. Ukrainian Journal of Surgery. 2012;1(16):76-83. (Ukrainian)
  9. Stepanov YM, Breslavets YS. Clinical experience in the use of biological hepatoprotector prohepar in the treatment of patients with hepatobiliary pathology (review). Gastroenterology. 2015;3(57):133-141. (Ukrainian)
  10. Stepanyan IA, Kobinets YV, Izranov VA, Ovchinnikov OI. Diffuse liver changes: assessment of ARFI-elastometry diagnostics efficacy. Diagnostic Radiology and Radiotherapy. 2018;(1):30-35. (Russian)
  11. Surkov AN, Namazova-Baranova LS, Vashakmadze ND, Hevorkian AK, Tomylova AY, Potapov AS et al. Transient elastography is a non-invasive method for diagnosing stages of liver fibrosis in children with rare diseases. Modern Technologies in Medicine. 2016;8(3):56-63. (Russian)
  12. Fedulenkova YY. Ultrasound and computed tomography aspects of the diagnosis of diffuse liver damage. Ukrainian Radiological Journal. 2015;23(2):24-29. (Ukrainian)
  13. Barr RG, Ferraioli G, Palmeri ML et al. Elastography assessment of liver fibrosis: Society of Radiologists in Ultrasound consensus conference statement. Ultrasound Q 2016;32(2):94-107.
  14. Barr RG. Elastography Still in Its Infancy. Radiology. 2018;288(1):107-108.
  15. Bruno C, Minniti S, Bucci A, Mucelli RP. ARFI: from basic principles to clinical applications in diffuse chronic disease – a review. Insights Imaging. 2016;7(5);735-746.
  16. Calès P, Boursier J, Lebigot J et al. Liver fibrosis diagnosis by blood test and elastography in chronic hepatitis C: agreement or combination? Aliment Pharmacol Ther. 2017;45(7):991-1003.
  17. Cassinotto C, Boursier J, de Lédinghen V et al. Liver stiffness in nonalcoholic fatty liver disease: A comparison of supersonic shear imaging, FibroScan, and ARFI with liver biopsy. Hepatology. 2016;63(6):1817-1827.
  18. Castera L, Chan HL, Arrese M et al. European Association for Study of Liver; Asociacion Latinoamericana para el Estudio del Higado. EASL-ALEH clinical practice guidelines: non-invasive tests for evaluation of liver disease severity and prognosis. J Hepatol. 2015;63(1):237-264.
  19. Cui J, Ang B, Haufe W et al. Comparative diagnostic accuracy of magnetic resonance elastography vs. eight clinical prediction rules for non-invasive diagnosis of advanced fibrosis in biopsy proven non-alcoholic fatty liver disease: a prospective study. Aliment Pharmacol Ther. 2015;41(12):1271-1280.
  20. Dietrich CF, Bamber J, Berzigotti A, Bota S, Cantisani V, Castera L et al. EFSUMB Guidelines and Recommendations on the Clinical Use of Liver Ultrasound Elastography, Update 2017 (Long Version). Ultraschall in Med. 2017;38:16-47.
  21. Eaton JE, Dzyubak B, Venkatesh SK et al. Performance of magnetic resonance elastography in primary sclerosing cholangitis. J Gastroenterol Hepatol. 2016;31(6):1184-1190.
  22. Ehlken H, Wroblewski R, Corpechot C et al. Validation of transient elastography and comparison with spleen length measurement for staging of fibrosis and clinical prognosis in primary sclerosing cholangitis. PLoS One. 2016;11(10):e0164224.
  23. Ekstedt M, Hagström H, Nasr P, Fredrikson M, Stål P, Kechagias S, Hultcrantz R. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology. 2015;61(5):1547-1454.
  24. European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64(6):1388-1402.
  25. European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2016. J Hepatol. 2017;66(1):153-194.
  26. Ferraioli G, Filice C, Castera L et al. WFUMB guidelines and recommendations for clinical use of ultrasound elastography. Part 3: liver. Ultrasound Med Biol 2015;41(5):1161-1179.
  27. Foncea C, Popescu A, Lupusoru R, Fofiu R, Sirli R, Danila M, Sporea I. Comparative study between pSWE and 2 D-SWE techniques integrated in the same ultrasound machine, with Transient Elastography as the reference method. Med Ultrason. 2020;1:13-19.
  28. Friedrich-Rust M, Poynard T, Castera L. Critical comparison of elastography methods to assess chronic liver disease. Nat Rev Gastroenterol Hepatol. 2016;13:402-411.
  29. Gerber L, Kasper D, Fitting D, Knop V, Vermehren A, Sprinzl K et al. Assessment of liver fibrosis with 2-D shear wave elastography in comparison to transient elastography and acoustic radiation force impulse imaging in patients with chronic liver disease. Ultrasound Med Biol. 2015;41:2350-2359.
  30. Gerstenmaier JF, Gibson RN. Ultrasound in chronic liver disease. Insights Imaging. 2014;5(4):441-455.
  31. Hu X, Qiu L, Liu D, Qian L. Acoustic radiation force impulse (ARFI) elastography for non-invasive evaluation of hepatic fibrosis in chronic hepatitis B and C patients: a systematic review and metaanalysis. Med Ultrason. 2017;19(1):23-31.
  32. Hudert CA, Tzschдtzsch H, Guo J et al. US time-harmonic elastography: detection of liver fibrosis in adolescents with extreme obesity with nonalcoholic fatty liver disease. Radiology. 2018;288:99-106.
  33. Jamialahmadi T, Nematy M, Jangjoo A, Goshayeshi L, Rezvani R, Ghaffarzadegan K, Nooghabi M et al. Measurement of liver stiffness with 2 D-shear wave elastography (2 D-SWE) in bariatric surgery candidates reveals acceptable diagnostic yield compared to liver biopsy. Obes Surg. 2019;29:2585-2592.
  34. Jiang T, Tian G, Zhao Q et al. Diagnostic accuracy of 2Dshear wave elastography for liver fibrosis severity: a meta-analysis. PLoS One. 2016;11(6):e0157219.
  35. Kennedy P, Wagner M, Castéra L et al. Quantitative Elastography Methods in Liver Disease: Current Evidence and Future Directions. Radiology. 2018;286(3):738-763.
  36. Kiani A, Brun V, Lainé F, et al. Acoustic radiation force impulse imaging for assessing liver fibrosis in alcoholic liver disease. World J Gastroenterol. 2016;22(20):4926-4935.
  37. Kim RG, Nguyen P, Bettencourt R, Dulai PS, Haufe W, Hooker J et al. Magnetic resonance elastography identifies fibrosis in adults with alpha-1 antitrypsin deficiency liver disease: a prospective study. Aliment Pharmacol Ther. 2016;44:287-299.
  38. Kwok R, Tse YK, Wong GL et al. Systematic review with meta-analysis: non-invasive assessment of non-alcoholic fatty liver disease – the role of transient elastography and plasma cytokeratin-18 fragments. Aliment Pharmacol Ther. 2014;39(3):254-269.
  39. Mauss S, Berg T, Rockstroh J. et al. Hepatology. Sydney: Flying Publisher, 2015; 655 p. Link: http://
  40. Nierhoff J, Cha´vez Ortiz AA, Herrmann E, Zeuzem S, Friedrich-Rust M. The efficiency of acoustic radiation force impulse imaging for the staging of liver fibrosis: A meta-analysis. Eur Radiol. 2013;23:3040-3053.
  41. Puigvehí M, Broquetas T, Coll S et al. Impact of anthropometric features on the applicability and accuracy of FibroScan(®) (M and XL) in overweight/obese patients. J Gastroenterol Hepatol. 2017;32(10):1746-1753.
  42. Reiter R, Wetzel M, Hamesch K, Strnad P, Asbach P, Haas M, Siegmund B. Comparison of non-invasive assessment of liver fibrosis in patients with alpha1-antitrypsin deficiency using magnetic resonance elastography (MRE), acoustic radiation force impulse (ARFI) Quantification, and 2D-shear wave elastography (2D-SWE). PLOS ONE. April 26, 2018 1/13.
  43. Serai SD, Obuchowski NA, Venkatesh SK et al. Repeatability of MR Elastography of Liver: A Meta-Analysis. Radiology. 2017;285(1):92-100.
  44. Shiina T, Nightingale KR, Palmeri ML et al. WFUMB guidelines and recommendations for clinical use of ultrasound elastography. Part 1: basic principles and terminology. Ultrasound Med Biol. 2015;41(5):1126-1147.
  45. Singh S, Venkatesh S, Loomba R, Wang Z, Sirlin C, Chen J et al. Magnetic resonance elastography for staging liver fibrosis in non-alcoholic fatty liver disease: a diagnostic accuracy systematic review and individual participant data pooled analysis. Eur Radiol. 2016;26:1431-1440.
  46. Singh S, Venkatesh SK, Wang Z et al. Diagnostic performance of magnetic resonance elastography in staging liver fibrosis: a systematic review and meta-analysis of individual participant data. Clin Gastroenterol Hepatol. 2015;13(3):440-451.
  47. Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63(1):261-283.
  48. Thiele M, Detlefsen S, Sevelsted Møller L, et al. Transient and 2-dimensional shear-wave elastography provide comparable assessment of alcoholic liver fibrosis and cirrhosis. Gastroenterology. 2016;150(1):123-133.
  49. Verlinden W, Bourgeois S, Gigase P et al. Liver fibrosis evaluation using real-time shear wave elastography in hepatitis C monoinfected and human immunodeficiency virus/hepatitis C-coinfected patients. J Ultrasound Med. 2016;35(6):1299-1308.
  50. Wagner M, Corcuera-Solano I, Lo G et al. Technical Failure of MR Elastography Examinations of the Liver: Experience from a Large Single-Center Study. Radiology. 2017;284(2):401-412.
  51. Wang J, Malik N, Yin M et al. Magnetic resonance elastography is accurate in detecting advanced fibrosis in autoimmune hepatitis. World J Gastroenterol. 2017;23(5):859-868.
  52. Woo H, Lee JY, Yoon JH, Kim W, Cho B, Choi BI. Comparison of the Reliability of Acoustic Radiation Force Impulse Imaging and Supersonic Shear Imaging in Measurement of Liver Stiffness. Radiology. 2015;277(3):881-886.
  53. Xu Q, Sheng L, Bao H et al. Evaluation of transient elastography in assessing liver fibrosis in patients with autoimmune hepatitis. J Gastroenterol Hepatol. 2017;32(3):639-644.
  54. Yada N, Sakurai T, Minami T et al. Influence of liver inflammation on liver stiffness measurement in patients with autoimmune hepatitis evaluation by combinational elastography. Oncology. 2017;92(Suppl 1):10-15.
  55. Zemlianitsyna OV, Sinaiko VM, Savenkov V I, Kravchun PP, Kravchun NO, Goncharova OA. A Non-invasive fibrosis markers and elastography in diagnosis of fibrosis severity in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease. Zaporozhye Medical Journal. 2020;22(1):48-53.
  56. Zhang W, Zhu Y, Zhang C, Ran H. Diagnostic Accuracy of 2‐Dimensional Shear Wave Elastography for the Staging of Liver Fibrosis: A Meta‐analysis. Journal of  Ultrasound in Medicine. 2019;38(3):733-740.