Objective evaluation of liver fibrosis using ultrasound microscopy

Main Article Content

Katsutoshi Miura Toshihide Iwashita

Abstract

Background: Chronic liver damage, such as viral hepatitis, causes liver fibrosis. Recently, the advent of interferon (INF) and antiviral drugs has reduced hepatitis viruses, enabling liver function recovery and fibrosis improvement. A quantitative assessment of liver fibrosis is mandatory to identify treatment efficacy.


Aim: We aimed to apply speed-of-sound (SOS) values for the objective assessment of fibrosis in liver biopsy because SOS values correlate with stiffness.


Methods: We differentiated SOS images of pre- and post-treatment INF liver. We then compared the SOS values with the fibrosis score and magnetic resonance elastography (MRE) values. We tried to digest sections with collagenase to clarify the process of fibrosis deletion.


Results: After INF therapy, SOS images demonstrated a marked reduction in fibrosis in the lobules. SOS values were well correlated with the fibrosis score and slightly corresponded to MRE values. Perisinusoidal fibrosis was susceptible to collagenase digestion. Portal areas were minimal.


Conclusion: The SOS value, which objectively evaluates fibrosis in tissue sections, is an excellent indicator. It assesses fibrosis progression and reduction post-treatment.

Article Details

How to Cite
MIURA, Katsutoshi; IWASHITA, Toshihide. Objective evaluation of liver fibrosis using ultrasound microscopy. Medical Research Archives, [S.l.], v. 12, n. 7, july 2024. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/5611>. Date accessed: 21 dec. 2024. doi: https://doi.org/10.18103/mra.v12i7.5611.
Section
Research Articles

References

1. Freeman AJ, Dore GJ, Law MG, et al. Estimating progression to cirrhosis in chronic hepatitis C virus infection. Hepatology. 2001;34(4 I):809-816. doi:10.1053/jhep.2001.27831

2. Saldarriaga OA, Dye B, Pham J, et al. Comparison of liver biopsies before and after direct-acting antiviral therapy for hepatitis C and correlation with clinical outcome. Sci Rep. 2021;11(1). doi:10.1038/s41598-021-93881-7

3. Chu CY, Cheng CH, Chen HL, et al. Long-term histological change in chronic hepatitis C patients who had received peginterferon plus ribavirin therapy with sustained virological response. Journal of the Formosan Medical Association. 2019;118(7):1129-1137. doi:10.1016/j.jfma.2018.11.005

4. Hsieh MH, Kao TY, Hsieh TH, et al. Long-term surveillance of liver histological changes in chronic hepatitis C patients completing pegylated interferon-α plus ribavirin therapy: an observational cohort study. Ther Adv Chronic Dis. 2022;13. doi:10.1177/20406223211067631

5. Shiffman ML, Sterling RK, Contos M, et al. Long Term Changes in Liver Histology Following Treatment of Chronic Hepatitis C Virus. Vol 13.; 2014.

6. Chen Z, Ma Y, Cai J, et al. Serum biomarkers for liver fibrosis. Clinica Chimica Acta. 2022;537. doi:10.1016/j.cca.2022.09.022

7. Faria SC, Ganesan K, Mwangi I, et al. MR imaging of liver fibrosis: Current state of the art. Radiographics. 2009;29(6):1615-1635. doi:10.1148/rg.296095512

8. Lin YS. Ultrasound Evaluation of Liver Fibrosis. J Med Ultrasound. 2017;25(3):127-129. doi:10.1016/j.jmu.2017.04.001

9. Ichida F, Tsuji T, Omata M, et al. New Inuyama classification; new criteria for histological assessment of chronic hepatitis. International Hepatology Communications. Iternational Hepatology Communications. 1996;6:112-119.

10. Goodman ZD. Grading and staging systems for inflammation and fibrosis in chronic liver diseases. J Hepatol. 2007;47(4):598-607. doi:10.1016/j.jhep.2007.07.006

11. Heyens LJM, Busschots D, Koek GH, Robaeys G, Francque S. Liver Fibrosis in Non-alcoholic Fatty Liver Disease: From Liver Biopsy to Non-invasive Biomarkers in Diagnosis and Treatment. Front Med (Lausanne). 2021;8. doi:10.3389/fmed.2021.615978

12. Astbury S, Grove JI, Dorward DA, Guha IN, Fallowfield JA, Kendall TJ. Reliable computational quantification of liver fibrosis is compromised by inherent staining variation. Journal of Pathology: Clinical Research. 2021;7(5):471-481. doi:10.1002/cjp2.227

13. Lo RC, Kim H. Histopathological evaluation of liver fibrosis and cirrhosis regression. Clin Mol Hepatol. 2017;23(4):302-307. doi:10.3350/cmh.2017.0078

14. Abe T, Hashiguchi A, Yamazaki K, et al. Quantification of collagen and elastic fibers using whole-slide images of liver biopsy specimens. Pathol Int. 2013;63(6):305-310. doi:10.1111/pin.12064

15. Saijo Y. Recent Applications of Acoustic Microscopy for Quantitative Measurement of Acoustic Properties of Soft Tissues. In: Mamou J, Oelze M, eds. Quantitative Ultrasound in Soft Tissues. Springer; 2013:291–313.
doi:10.1007/978-94-007-6952-6_12

16. Miura K. Application of Scanning Acoustic Microscopy to Pathological Diagnosis. In: Stanciu SG, ed. Microscopy and Analysis. Intech; 2016: 381-403. doi:10.5772/63405

17. Saijo Y, Filho E, Sasaki H, et al. Ultrasonic Tissue Characterization of Atherosclerosis by a Speed-of-Sound Microscanning System. IEEE Trans Ultrason Ferroelectr Freq Control. 2007;54(8):1571 -1577.

18. Saijo Y. Acoustic microscopy: latest developments and applications. Imaging Med. 2009; 1(1):47-63. doi:http://dx.doi.org/10.2217/iim.09.8

19. Azhari H. Appendix A: Typical Acoustic Properties of Tissues. Basics of Biomedical Ultrasound for Engineers. Published online 2010: 313-314. doi:10.1002/9780470561478.app1

20. Miura K, Mineta H. Histological evaluation of thyroid lesions using a scanning acoustic microscope. Pathol Lab Med Int. 2014;6:1-9.

21. Miura K, Yamamoto S. Histological imaging from speed-of-sound through tissues by scanning acoustic microscopy (SAM). Protoc Exch. Published online 2013. doi:10.1038/protex.2013.040

22. Tamura K, Ito K, Yoshida S, Mamou J, Miura K, Yamamoto S. Alteration of speed-of-sound by fixatives and tissue processing methods in scanning acoustic microscopy. Front Phys. 2023;11. doi:10.3389/fphy.2023.1060296

23. Hozumi N, Yamashita R, Lee CK, et al. Time-frequency analysis for pulse driven ultrasonic microscopy for biological tissue characterization. In: Ultrasonics. Vol 42. ; 2004:717-722. doi:10.1016/j.ultras.2003.11.005

24. Miura K, Yamashita K. Mechanical weakness of thoracic aorta related to aging or dissection predicted by speed of sound with collagenase. Ultrasound Med Biol. 2019;45(12):3102-3115. doi:10.1016/j.ultrasmedbio.2019.08.012

25. Meziri M, Pereira WCA, Abdelwahab A, Degott C, Laugier P. In vitro chronic hepatic disease characterization with a multiparametric ultrasonic approach. Ultrasonics. 2005;43(5):305-313. doi:10.1016/j.ultras.2004.09.002

26. Bamber JC, Hill CR. Acoustic properties of normal and cancerous human liver-1. Dependence on pathological condition. Ultrasound in Med & Biol. 1981;7:121-133.

27. Irie S, Inoue K, Yoshida K, et al. Speed of sound in diseased liver observed by scanning acoustic microscopy with 80 MHz and 250 MHz. J Acoust Soc Am. 2016;139(1):512-519. doi:10.1121/1.4940126

28. Uceda AB, Mariño L, Casasnovas R, Adrover M. An overview on glycation: molecular mechanisms, impact on proteins, pathogenesis, and inhibition. Biophys Rev. 2024;16(2):189-218. doi:10.1007/s12551-024-01188-4

29. Miura K, Katoh H. Structural and histochemical alterations in the aortic valves of elderly patients: a comparative study of aortic stenosis, aortic regurgitation, and normal valves. Biomed Res Int. Published online 2016. doi:10.1155/2016/6125204

30. Miura K, Yamashita K. Evaluation of aging, diabetes mellitus, and skin wounds by scanning acoustic microscopy with protease digestion. Pathobiology of Aging & Age-related Diseases. Published online 2018.
doi:10.1080/20010001.2018.1516072

31. Miura K. Histological and mechanical information based on biochemical alterations of cardiovascular diseases using scanning acoustic microscopy with P proteinases : A novel technique for cardiovascular research. Atherosclerosis: Open Access. 2021;6(2).

32. Cheng D, Chai J, Wang H, Fu L, Peng S, Ni X. Hepatic macrophages: Key players in the development and progression of liver fibrosis. Liver International. 2021;41(10):2279-2294. doi:10.1111/liv.14940

33. Sufleţel RT, Melincovici CS, Gheban BA, Toader Z, Mihu CM. Hepatic stellate cells - from past till present: Morphology, human markers, human cell lines, behavior in normal and liver pathology. Romanian Journal of Morphology and Embryology. 2020;61(3):615-642. doi:10.47162/RJME.61.3.01