ISSN 1001-5256
CN 22-1108/R
Volume 39 Issue 1
Jan.  2023
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Article Contents

Research advances in the reversal of liver fibrosis

DOI: 10.3969/j.issn.1001-5256.2023.01.030
Research funding:

Social Development Project of Shanxi Key Research and Development Plan 201903D321188;

Department of Science and Technology of Shanxi Province, General Project 20210302123258

More Information
  • Corresponding author: FENG Duiping, fengdp@sxmu.edu.cn (ORCID: 0000-0003-4516-3797)
  • Received Date: 2022-05-15
  • Accepted Date: 2022-07-14
  • Published Date: 2023-01-20
  • Chronic liver injury caused by any etiology will lead to liver fibrosis, and it was believed in the past that liver fibrosis is a static and irreversible pathophysiological process. In recent years, with the rapid development of molecular biology and the in-depth research on the microscopic aspect of the liver, more and more evidence has shown that liver fibrosis is a dynamic and reversible process. This article reviews the reports of different methods for evaluating the reversal of liver fibrosis caused by various etiologies, summarizes the pathogenesis and reversal mechanism of liver fibrosis, reviews the therapeutic drugs for reversal, and summarizes the current evaluation methods for liver fibrosis, and finally, it is believed that timely clearance or control of potential etiology may help to achieve the reversal of liver fibrosis to a certain degree.


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  • [1]
    AYDIN MM, AKÇALI KC. Liver fibrosis[J]. Turk J Gastroenterol, 2018, 29(1): 14-21. DOI: 10.5152/tjg.2018.17330.
    ZOUBEK ME, TRAUTWEIN C, STRNAD P. Reversal of liver fibrosis: From fiction to reality[J]. Best Pract Res Clin Gastroenterol, 2017, 31(2): 129-141. DOI: 10.1016/j.bpg.2017.04.005.
    CHEN S, ZHOU J, WU X, et al. Comparison of fibrosis regression of entecavir alone or combined with pegylated interferon alpha2a in patients with chronic hepatitis B[J]. Hepatol Int, 2021, 15(3): 611-620. DOI: 10.1007/s12072-021-10162-1.
    ZAKAREYA T, ELHELBAWY M, ELZOHRY H, et al. Long-term impact of hepatitis C virus eradication on liver stiffness in egyptian patients[J]. Can J Gastroenterol Hepatol, 2021, 2021: 4961919. DOI: 10.1155/2021/4961919.
    NONO JK, FU K, MPOTJE T, et al. Investigating the antifibrotic effect of the antiparasitic drug Praziquantel in in vitro and in vivo preclinical models[J]. Sci Rep, 2020, 10(1): 10638. DOI: 10.1038/s41598-020-67514-4.
    DIENSTAG JL, GOLDIN RD, HEATHCOTE EJ, et al. Histological outcome during long-term lamivudine therapy[J]. Gastroenterology, 2003, 124(1): 105-117. DOI: 10.1053/gast.2003.50013.
    ABAYLI B, ABAYLI C, GENCDAL G. Histopathological evaluation of long-term tenofovir disoproxil fumarate treatment in patients with hepatitis be antigen-negative chronic hepatitis B[J]. World J Gastrointest Pharmacol Ther, 2021, 12(2): 32-39. DOI: 10.4292/wjgpt.v12.i2.32.
    SUN YM, CHEN SY, YOU H. Regression of liver fibrosis: evidence and challenges[J]. Chin Med J (Engl), 2020, 133(14): 1696-1702. DOI: 10.1097/CM9.0000000000000835.
    ZENG DB, DI L, ZHANG RC, et al. The effect of splenectomy on the reversal of cirrhosis: a prospective study[J]. Gastroenterol Res Pract, 2019, 2019: 5459427. DOI: 10.1155/2019/5459427.
    赵艳玲. 肝硬化门脉高压TIPS术前后肝纤维化指标的变化分析[D]. 西宁: 青海大学, 2019.

    ZHAO YL. Cirrhosis portal hypertension liver fibrosis before and after TIPS Change analysis of indicators[D]. Xining: Qinghai University, 2019.
    PANG N, ZHAO C, LI J, et al. Body mass index changes after transjugular intrahepatic portosystemic shunt in individuals with cirrhosis[J]. Nutrition, 2021, 84: 111095. DOI: 10.1016/j.nut.2020.111095.
    MATSUDA M, SEKI E. Hepatic stellate cell-macrophage crosstalk in liver fibrosis and carcinogenesis[J]. Semin Liver Dis, 2020, 40(3): 307-320. DOI: 10.1055/s-0040-1708876.
    KISSELEVA T, BRENNER D. Molecular and cellular mechanisms of liver fibrosis and its regression[J]. Nat Rev Gastroenterol Hepatol, 2021, 18(3): 151-166. DOI: 10.1038/s41575-020-00372-7.
    XUE Y, QIAN K, SUN Y, et al. Application of TGF-β1, TIMP-1 and TIMP-2 small interfering RNAs can alleviate CCl4-induced hepatic fibrosis in rats by rebalancing Th1/Th2 cytokines[J]. Exp Ther Med, 2021, 22(3): 963. DOI: 10.3892/etm.2021.10395.
    LACHOWSKI D, CORTES E, RICE A, et al. Matrix stiffness modulates the activity of MMP-9 and TIMP-1 in hepatic stellate cells to perpetuate fibrosis[J]. Sci Rep, 2019, 9(1): 7299. DOI: 10.1038/s41598-019-43759-6.
    ZHANG J, LIU Y, CHEN H, et al. MyD88 in hepatic stellate cells enhances liver fibrosis via promoting macrophage M1 polarization[J]. Cell Death Dis, 2022, 13(4): 411. DOI: 10.1038/s41419-022-04802-z.
    European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection[J]. J Hepatol, 2017, 67(2): 370-398. DOI: 10.1016/j.jhep.2017.03.021.
    CAMPANA L, ESSER H, HUCH M, et al. Liver regeneration and inflammation: from fundamental science to clinical applications[J]. Nat Rev Mol Cell Biol, 2021, 22(9): 608-624. DOI: 10.1038/s41580-021-00373-7.
    SHOKRAVI S, BORISOV V, ZAMAN BA, et al. Mesenchymal stromal cells (MSCs) and their exosome in acute liver failure (ALF): a comprehensive review[J]. Stem Cell Res Ther, 2022, 13(1): 192. DOI: 10.1186/s13287-022-02825-z.
    WU W, LI L, YANG J, et al. Therapeutic effect of biejiaxiaozheng pills on carbon tetrachloride-induced hepatic fibrosis in rats through the NF-κB/Nrf2 pathway[J]. Gastroenterol Res Pract, 2021, 2021: 3954244. DOI: 10.1155/2021/3954244.
    KAMM DR, MCCOMMIS KS. Hepatic stellate cells in physiology and pathology[J]. J Physiol, 2022, 600(8): 1825-1837. DOI: 10.1113/JP281061.
    KUMAR V, XIN X, MA J, et al. Therapeutic targets, novel drugs, and delivery systems for diabetes associated NAFLD and liver fibrosis[J]. Adv Drug Deliv Rev, 2021, 176: 113888. DOI: 10.1016/j.addr.2021.113888.
    JIANG H, LIU J, ZHANG K, et al. Saikosaponin D inhibits the proliferation and promotes the apoptosis of rat hepatic stellate cells by inducing autophagosome formation[J]. Evid Based Complement Alternat Med, 2021, 2021: 5451758. DOI: 10.1155/2021/5451758.
    XIU AY, DING Q, LI Z, et al. Doxazosin attenuates liver fibrosis by inhibiting autophagy in hepatic stellate cells via activation of the PI3K/Akt/mTOR signaling pathway[J]. Drug Des Devel Ther, 2021, 15: 3643-3659. DOI: 10.2147/DDDT.S317701.
    YU HX, YAO Y, BU FT, et al. Blockade of YAP alleviates hepatic fibrosis through accelerating apoptosis and reversion of activated hepatic stellate cells[J]. Mol Immunol, 2019, 107: 29-40. DOI: 10.1016/j.molimm.2019.01.004.
    GUO Q, CHEN M, CHEN Q, et al. Silencing p53 inhibits interleukin 10-induced activated hepatic stellate cell senescence and fibrotic degradation in vivo[J]. Exp Biol Med (Maywood), 2021, 246(4): 447-458. DOI: 10.1177/1535370220960391.
    CIERPKA R, WEISKIRCHEN R, ASIMAKOPOULOS A. Perilipin 5 ameliorates hepatic stellate cell activation via SMAD2/3 and SNAIL signaling pathways and suppresses STAT3 activation[J]. Cells, 2021, 10(9): 2184. DOI: 10.3390/cells10092184.
    MIRANDA JF, SCARINCI LD, RAMOS LF, et al. The modulatory effect of triclosan on the reversion of the activated phenotype of LX-2 hepatic stellate cells[J]. J Biochem Mol Toxicol, 2020, 34(1): e22413. DOI: 10.1002/jbt.22413.
    LI D, LI W, CHEN Y, et al. Anti-fibrotic role and mechanism of Periplaneta americana extracts in CCl4-induced hepatic fibrosis in rats[J]. Acta Biochim Biophys Sin (Shanghai), 2018, 50(5): 491-498. DOI: 10.1093/abbs/gmy024.
    MANKA P, ZELLER A, SYN WK. Fibrosis in chronic liver disease: An update on diagnostic and treatment modalities[J]. Drugs, 2019, 79(9): 903-927. DOI: 10.1007/s40265-019-01126-9.
    TIAN G, KONG D, JIANG T, et al. Complications after percutaneous ultrasound-guided liver biopsy: A systematic review and meta-analysis of a population of more than 12, 000 patients from 51 cohort studies[J]. J Ultrasound Med, 2020, 39(7): 1355-1365. DOI: 10.1002/jum.15229.
    BOYD A, CAIN O, CHAUHAN A, et al. Medical liver biopsy: background, indications, procedure and histopathology[J]. Frontline Gastroenterol, 2020, 11(1): 40-47. DOI: 10.1136/flgastro-2018-101139.
    LEOW WQ, BEDOSSA P, LIU F, et al. An improved qfibrosis algorithm for precise screening and enrollment into non-alcoholic steatohepatitis (NASH) clinical trials[J]. Diagnostics (Basel), 2020, 10(9): 643. DOI: 10.3390/diagnostics10090643.
    DONG M, WU J, YU X, et al. Validation and comparison of seventeen noninvasive models for evaluating liver fibrosis in Chinese hepatitis B patients[J]. Liver Int, 2018, 38(9): 1562-1570. DOI: 10.1111/liv.13688.
    MÁIZ CARRO L, MARTÍNEZ-GARCÍA MA. Use of Hyaluronic Acid (HA) in chronic airway diseases[J]. Cells, 2020, 9(10): 2210. DOI: 10.3390/cells9102210.
    KIM EM, PARK JW, LEE SM, et al. Diagnostic performance of 2-D shear wave elastography on the evaluation of hepatic fibrosis with emphasis on impact of the different region-of-interest methods[J]. Ultrasound Med Biol, 2022, 48(2): 198-208. DOI: 10.1016/j.ultrasmedbio.2021.09.020.
    CUI XW, LI KN, YI AJ, et al. Ultrasound elastography[J]. Endosc Ultrasound, 2022. DOI: 10.4103/EUS-D-21-00151.[OnlineaheadofPrint]
    LEFEBVRE T, WARTELLE-BLADOU C, WONG P, et al. Prospective comparison of transient, point shear wave, and magnetic resonance elastography for staging liver fibrosis[J]. Eur Radiol, 2019, 29(12): 6477-6488. DOI: 10.1007/s00330-019-06331-4.
    WU CY, HSIEH HH, CHU PA, et al. Comparison of 18F-FDG, 18F-Fluoroacetate, and 18F-FEPPA for imaging liver fibrosis in a bile duct-ligated rat model[J]. Mol Imaging, 2021, 2021: 7545284. DOI: 10.1155/2021/7545284.
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