MOLECULAR DIAGNOSIS OF FIBROSIS IN DIFFUSE LIVER DISEASES

Chronic liver diseases (CLD) held an important place in the structure of pediatric hepatology including viral and autoimmune hepatitis, various forms of liver pathology caused by metabolic disorders. They are characterized by a variety of clinical manifestations, a progressive course with the formation of fibrosis and the possibility of its outcome in liver cirrhosis (LC). Liver puncture biopsy with morphological examination of its tissue is the leading method for determining the stage of liver fibrosis (LF) in CLD children. However, it is not always safe for the patient. Using non-invasive imaging methods, it is impossible to detect intermediate stages of fibrosis and it is not always possible to detect signs of CL. Therefore, non-invasive markers of LF, based on the identification of various molecular compounds involved in the formation of components of the extracellular matrix (ECM) or acting as activators of fibrogenesis, are necessary. Hyaluronic acid, collagen type IV, matrix metalloproteinases-2 and -9, a tissue inhibitor of matrix metalloproteinases-1, transforming growth factor beta1, showing diagnostic value for non-invasive monitoring of the development of LF, are well studied among them.

Caviglia GP, Rosso C, Fagoonee S, Saracco GM, Pellicano R. Liver fibrosis: the 2017 state of art. Panminerva Med. 2017; 59(4): 320-31.

Bataller R., Brenner D. A. Liver fibrosis. J. Clin. Invest. 2005; 115(2): 209-18.

Parola M, Pinzani M. Liver fibrosis: Pathophysiology, pathogenetic targets and clinical issues. Mol Aspects Med. 2019; 65(1): 37-55.

Shen WJ, Chen G, Wang M, Zheng S. Liver fibrosis in biliary atresia. World J Pediatr. 2018. doi: 10.1007/s12519-018-0203-1.

Hudert CA, Selinski S, Rudolph B, Bläker H, Loddenkemper C, Thielhorn R et al. Genetic determinants of steatosis and fibrosis progression in paediatric non-alcoholic fatty liver disease. Liver Int. 2018. doi: 10.1111/liv.14006.

Capone K, Azzam RK. Wilson’s Disease: A Review for the General Pediatrician. Pediatr Ann. 2018; 47(11): 440-4.

Li Z.X., He Y., Wu J. Noninvasive evaluation of hepatic fibrosis in children with infant hepatitis syndrome. World J. Gastroenterol. 2006; 12(44): 7155-60.

Nobili V., Parkes J., Bottazzo G. Performance of ELF Serum Markers in Predicting Fibrosis Stage in Pediatric Non-Alcoholic Fatty Liver Disease. Gastroenterology. 2009; 136(1): 160-7.

Ray K. Liver: Key role for αv integrins in myofibroblasts in liver fibrosis. Nat Rev Gastroenterol Hepatol. 2014; 11: 4. DOI: 10.1038/nrgastro.2013.227.

Ying HZ, Chen Q, Zhang WY, Zhang HH, Ma Y, Zhang SZ et al. PDGF signaling pathway in hepatic fibrosis pathogenesis and therapeutics (Review). Mol Med Rep. 2017; 16(6): 7879-89.

Bataller R, Brenner DA. Liver fibrosis. J Clin Invest. 2005; 115(2): 209-18.

Weiskirchen R, Weiskirchen S, Tacke F. Organ and tissue fibrosis: Molecular signals, cellular mechanisms and translational implications. Mol Aspects Med. 2019; 65(1): 2-15.

Seki E, Brenner DA. Recent advancement of molecular mechanisms of liver fibrosis. J Hepatobiliary Pancreat Sci. 2015; 22(7): 512-8.

Sato K, Kennedy L, Liangpunsakul S, Kusumanchi P, Yang Z, Meng F et al. Intercellular Communication between Hepatic Cells in Liver Diseases. Int J Mol Sci. 2019; 20(9). doi: 10.3390/ijms20092180.

Li CJ, Yang ZH, Lu FG, Shi XL, Liu DL. Clinical significance of fibrotic, haemostatic and endotoxic changes in patients with liver cirrhosis. Acta Gastroenterol Belg. 2018; 81(3): 404-9.

Volynets G.V., Nikitin A.V., Skvortsova T.A., Potapov A.S., Gevorkyan A.K., Smirnov I.E. Features of diagnosis of biliary atresia in children. Rossiyskiy pediatricheskiy zhurnal. 2017; 20(2): 79-84. (in Russian)

Ruzman L, Mikolasevic I, Baraba Dekanic K, Milic S, Palcevski G. Advances in diagnosis of chronic liver diseases in pediatric patients. World J Pediatr. 2018; 14(6): 541-7.

Chapin CA, Bass LM. Cirrhosis and Portal Hypertension in the Pediatric Population. Clin Liver Dis. 2018; 22(4): 735-52.

Borkham-Kamphorst E, Weiskirchen R. The PDGF system and its antagonists in liver fibrosis. Cytokine Growth Factor Rev. 2016; 28(1): 53-61.

Elpek GÖ. Cellular and molecular mechanisms in the pathogenesis of liver fibrosis: An update. World J Gastroenterol. 2014; 20(23): 7260-76.

Nielsen J, Christensen VB, Borgwardt L, Rasmussen A, Østrup O, Kjær MS. Prognostic molecular markers in pediatric liver disease - Are there any? Biochim Biophys Acta Mol Basis Dis. 2019; 1865(3): 577-86.

Smirnova G.I., Rumyantsev R.E. Vitamin D and allergic diseases in children. Rossiyskiy pediatricheskiy zhurnal. 2017; 20 (3): 166-72. (in Russian)

Thanapirom K, Suksawatamnuay S, Sukeepaisarnjaroen W, Treeprasertsuk S, Tanwandee T, Charatcharoenwitthaya P et al. Vitamin D-Binding protein Gene Polymorphism Predicts Pegylated Interferon-Related HBsAg Seroclearance in HBeAg-Negative Thai Chronic Hepatitis B Patients: A Multicentre Study. Asian Pac J Cancer Prev. 2019; 20(4): 1257-64.

Ramadan HK, Makhlouf NA, Mahmoud AA, Abd Elrhman M, El-Masry MA. Role of vitamin D deficiency as a risk factor for infections in cirrhotic patients. Clin Res Hepatol Gastroenterol. 2019; 43(1): 51-7.

Udomsinprasert W, Jittikoon J. Vitamin D and liver fibrosis: Molecular mechanisms and clinical studies. Biomed Pharmacother. 2019; 109: 1351-60.

Liangpunsakul S, Chalasani N. Lipid mediators of liver injury in nonalcoholic fatty liver disease. Am J Physiol Gastrointest Liver Physiol. 2019; 316(1): 75-81.

Bessone F, Razori MV, Roma MG. Molecular pathways of nonalcoholic fatty liver disease development and progression. Cell Mol Life Sci. 2019; 76(1): 99-128.

Procopet B, Cristea VM, Robic MA, Grigorescu M, Agachi PS, Metivier S et al. Serum tests, liver stiffness and artificial neural networks for diagnosing cirrhosis and portal hypertension. Dig Liver Dis. 2015; 47(5): 411-6.

Colloredo G., Guido M., Sonzogni A. Impact of liver biopsy size on histological evaluation of chronic viral hepatitis: the smaller the sample, the milder disease. J. Hepatol. 2003; 39(2): 239-44.

Sharma S, Khalili K, Nguyen GC. Non-invasive diagnosis of advanced fibrosis and cirrhosis. World J Gastroenterol. 2014; 20(45): 16820-30.

Dvoryakovskaya G.V., Ivleva S.A., Dvoryakovskiy I.V., Potapov A.S., Chetkina T.S., Smirnov I.E. Possibilities of ultrasonic diagnostics in assessment of extent of fibrosis (stage) in children with chronic hepatitises. Rossiyskiy pediatricheskiy zhurnal. 2013; 2: 31-8. (in Russian)

Ivleva S.A., Dvoryakovskaya G.V., Dvoryakovskiy I.V., Potapov A.S., Volynets G.V., Smirnov I.E. The innovative ultrasonic method of assessment of the liver parenchyma in children with chronic hepatitis C. Rossiyskiy pediatricheskiy zhurnal. 2015; 18 (3): 9-14. (in Russian)

Dvoryakovskaya G.M., Ivleva S.A., Dvoryakovskiy I.V., Surkov A.N., Potapov A.S., Gundobina O.S., Smirnov I.E. Comprehensive ultrasound diagnosis in the evaluation of liver parenchyma and stages of fibrosis in children with autoimmune hepatitis. Rossiyskiy pediatricheskiy zhurnal. 2016; 19 (1): 4-8. (in Russian)

Dvoryakovskiy I.V., Ivleva S.A., Dvoryakovskaya G.V., Surkov A.N., Potapov A.S., Smirnov I.E. Modern technologies of ultrasound diagnostics of cirrhosis in chronic liver diseases in children. Rossiyskiy pediatricheskiy zhurnal. 2016; 19(4): 202-8. (in Russian)

Ivleva S.A., Dvoryakovskiy I.V., Smirnov I.E. Modern non-invasive methods of diagnosis of liver fibrosis in children. Rossiyskiy pediatricheskiy zhurnal. 2017; 20(5): 300-6. (in Russian)

Serai SD, Trout AT, Miethke A, Diaz E, Xanthakos SA, Dillman JR. Putting it all together: established and emerging MRI techniques for detecting and measuring liver fibrosis. Pediatr Radiol. 2018; 48(9): 1256-72.

Petitclerc L, Gilbert G, Nguyen BN, Tang A. Liver Fibrosis Quantification by Magnetic Resonance Imaging. Top Magn Reson Imaging. 2017; 26(6): 229-41.

Lubner MG, Pickhardt PJ. Multidetector computed tomography for assessment of hepatic fibrosis. Clin Liver Dis (Hoboken). 2018; 11(6): 156-61.

Tovo CV, Villela-Nogueira CA, Leite NC, Panke CL, Port GZ, Fernandes S et al. Transient hepatic elastography has the best performance to evaluate liver fibrosis in non-alcoholic fatty liver disease (NAFLD). Ann Hepatol. 2019. doi: 10.1016/j.aohep.2018.09.003.

Thumar V, Squires JH, Spicer PJ, Robinson AL, Chan SS. Ultrasound Elastography Applications in Pediatrics. Ultrasound Q. 2018; 34(4): 199-205.

Andersen SB, Ewertsen C, Carlsen JF, Henriksen BM, Nielsen MB. Ultrasound Elastography Is Useful for Evaluation of Liver Fibrosis in Children-A Systematic Review. J Pediatr Gastroenterol Nutr. 2016; 63(4): 389-99.

Roccarina D, Rosselli M, Genesca J, Tsochatzis EA. Elastography methods for the non-invasive assessment of portal hypertension. Expert Rev Gastroenterol Hepatol. 2018; 12(2): 155-64.

Paternostro R, Reiberger T, Bucsics T. Elastography-based screening for esophageal varices in patients with advanced chronic liverdisease. World J Gastroenterol. 2019; 25(3): 308-29.

Thiele M, Kjaergaard M, Thielsen P, Krag A. Contemporary use of elastography in liver fibrosis and portal hypertension. Clin Physiol Funct Imaging. 2017; 37(3): 235-42.

Baranov A.A., Namazova-Baranova L.S., Smirnov I.E., Komarova N.L., Nikitin A.V., Gerasimova N.P., Kustova O.V. Modern nuclear medicine in pediatrics. Rossiyskiy pediatricheskiy zhurnal. 2015; 18(4): 4-13. (in Russian)

Surkov A.N., Smirnov I.E., Kucherenko A.G., Potapov A.S., Tumanova E.L. The dynamics of markers of fibrosis in chronic liver diseases in children. Rossiyskiy pediatricheskiy zhurnal. 2009; 3: 23-7.(In Russian)

Marek B., Kajdaniuk D., Janczewska-Kazek E. et al. Serum aminoterminal peptide of type III procollagen (PIIINP) and transforming growth factor-beta1 (TGF-beta1) levels in patients with chronic hepatitis B and C. Pol. Arch. Med. Wewn. 2003; 109(6): 603-8.

Lebensztein D.M., Sobaniec-Lotowska M., Kaczmarski M. Serum concentration of transforming growth factor (TGF)-beta 1 does not predict advanced liver fibrosis in children with chronic hepatitis B. Hepatogastroenterology. 2004; 51(55): 229-33.

Lebensztein DM, Skiba E, Sobaniec-Łotowska ME, Kaczmarski M.et al. Matrix metalloproteinases and their tissue inhibitors in children with chronic hepatitis B treated with lamivudine. Adv. Med. Sci. 2007; 52(1): 114-9.

Prasidthrathsint K, Stapleton JT. Laboratory Diagnosis and Monitoring of Viral Hepatitis. Gastroenterol Clin North Am. 2019; 48(2): 259-79.

Zuberbuhler F, Boursier J. Noninvasive diagnosis of liver fibrosis in NAFLD: Tips tricks. Clin Res Hepatol Gastroenterol. 2019. doi: 10.1016/j.clinre.2019.03.009.

Pardee M. Diagnosis and Management of Hepatitis B and C. Nurs Clin North Am. 2019; 54(2): 277-84.

Sun M, Kisseleva T. Reversibility of liver fibrosis. Clin Res Hepatol Gastroenterol. 2015; 39(1): 60-3.

Pavlov Ch.S., Zolotarevskiy V.B., Tomkevich M.C. Possibility of reversibility of liver cirrhosis (clinical and pathogenetic prerequisites). Rossiyskiy zhurnal gastroenterologii, gepatologii, koloproktologii. 2006; 16(1): 20-9. (In Russian)

Campana L, Iredale JP. Regression of Liver Fibrosis. Semin Liver Dis. 2017; 37(1): 1-10.

Huang Y, Deng X, Liang J. Modulation of hepatic stellate cells and reversibility of hepatic fibrosis. Exp Cell Res. 2017; 352(2): 420-6.

Schwabe RF, Luedde T. Apoptosis and necroptosis in the liver: a matter of life and death. Nat Rev Gastroenterol Hepatol. 2018; 15(12): 738-52.

Hu SJ, Jiang SS, Zhang J, Luo D, Yu B, Yang LY et al. Effects of apoptosis on liver aging. World J Clin Cases. 2019; 7(6): 691-704.

Schuppan D, Ashfaq-Khan M, Yang AT, Kim YO. Liver fibrosis: Direct antifibrotic agents and targeted therapies. Matrix Biol. 2018; 68-69: 435-51.

Fiorucci S, Biagioli M, Distrutti E. Future trends in the treatment of non-alcoholic steatohepatitis. Pharmacol Res. 2018; 134: 289-98.

Hung TH, Tsai CC, Lee HF. Statin use in cirrhotic patients with infectious diseases: A population-based study. PLoS One. 2019; 14(4). doi: 10.1371/journal.pone.0215839.

Poilil Surendran S, George Thomas R, Moon MJ, Jeong YY. Nanoparticles for the treatment of liver fibrosis. Int J Nanomedicine. 2017; 12: 6997-7006. doi: 10.2147/IJN.S145951.

Itaba N, Kono Y, Watanabe K, Yokobata T, Oka H, Osaki M et al. Reversal of established liver fibrosis by IC-2-engineered mesenchymal stem cell sheets. Sci Rep. 2019; 9(1): 6841. doi: 10.1038/s41598-019-43298-0.