Modern hepatoprotection: a narrative review of existing approaches and prospects for the use of biotechnological drugs
DOI:
https://doi.org/10.34287/MMT.3(58).2023.9Abstract
The prevalence of acute and chronic liver diseases is increasing worldwide, which affects the quality of life and can lead to dangerous, life-threatening complications. Almost 50.0 % of all cases of acute liver failure are caused by drugs, and the overall mortality due to drug-induced liver injury reaches 5.0–11.9 %. In 2020, the hospital incidence of diseases of the digestive organs in Ukraine amounted to 430,593 cases among the adult population, of which 11,976 were fatal.
The aim of the study: to characterize modern approaches to hepatoprotection and prospects of biological therapy based on data from open sources of information.
Materials and methods. Publications were selected based on the PubMed, ClinicalKey Elsevier, Cochrane Library, eBook Business Collection, and Google Scholar databases, which covered information about modern approaches to the treatment of liver diseases.
Results. Patients with chronic liver disease are at risk of extrahepatic complications related to liver cirrhosis and portal hypertension, as well as organ-specific complications of certain liver diseases. These complications can impair the quality of life and increase morbidity and mortality before and after liver transplantation. With chronic damage to the liver by toxic substances, the development of fatty dystrophy against the background of connective tissue changes in the form of nonspecific reactive hepatitis is more often observed. Hepatoprotectors are a pharmacotherapeutic group of heterogeneous drugs that prevent the destruction of cell membranes and stimulate the regeneration of hepatocytes. According to the Anatomical Therapeutic and Chemical classification of drugs (ATC classification), hepatoprotectors take their place in the group of drugs affecting the digestive system and metabolism (A), intended for the treatment of diseases of the liver and biliary tract (A05). One of the promising directions of biological therapy in patients with liver pathology is the use of means obtained from the fetoplacental complex.
Conclusions. Cell therapy in clinically significant volumes is an actual area of modern hepatology. The most promising directions of biological therapy in clinical hepatology are the use of mesenchymal stem cells, agents obtained from the fetoplacental complex, and gene therapy.
References
Ray G. Management of liver diseases: Current perspectives. World J Gastroenterol. 2022;28(40):5818-26. doi: 10.3748/wjg.v28.i40.5818.
Garcia-Cortes M, Garcia-Garcia A. Management of pharmacologic adverse effects in advanced liver disease. Clinical Drug Investigation. 2022;42(Suppl. 1):33-8. doi: 10.1007/s40261-022-01150-w.
Hamilton LA, Collins-Yoder A, Collins RE. Drug-induced liver injury. AACN Advanced Critical Care. 2016;27(4):430-40. doi: 10.4037/aacnacc2016953.
Licata A, Minissale MG, Calvaruso V, Craxì A. A focus on epidemiology of drug-induced liver injury: analysis of a prospective cohort. Eur Rev Med Pharmacol Sci. 2017;21(1 Suppl):112-21.
Safiri S, Kolahi AA, Noori M, Nejadghaderi SA, Karamzad N, Bragazzi NL, et al. Burden of anemia and its underlying causes in 204 countries and territories, 1990-2019: results from the Global Burden of Disease Study 2019. J Hematol Oncol. 2021;14(1):185. doi: 10.1186/s13045-021-01202-2.
Karlsen TH, Sheron N, Zelber-Sagi S, Carrieri P, Dusheiko G, Bugianesi E, Pryke R, Hutchinson SJ, et al. The EASL-Lancet Liver Commission: protecting the next generation of Europeans against liver disease complications and premature mortality. Lancet. 2022;399(10319):61-116. doi: 10.1016/ S0140-6736(21)01701-3.
Muriel P. The liver: general aspects and epidemiology. In: Muriel P., editor. Liver Pathophysiology: Therapies and Antioxidants. Elsevier; Waltham, MA: 2017. pp. 3-22.
Marcellin P, Kutala BK. Liver diseases: A major, neglected global public health problem requiring urgent actions and large-scale screening. Liver Int. 2018;38 Suppl 1:2-6. doi: 10.1111/liv.13682.
Scaglione S, Kliethermes S, Cao G, Shoham D, Durazo R, Luke A, et al. The Epidemiology of Cirrhosis in the United States: A Population-based Study. J Clin Gastroenterol. 2015;49(8):690-6. doi: 10.1097/MCG.0000000000000208.
Marcellin P, Pequignot F, Delarocque-Astagneau E, Zarski JP, Ganne N, Hillon P, et al. Mortality related to chronic hepatitis B and chronic hepatitis C in France: evidence for the role of HIV coinfection and alcohol consumption. J Hepatol. 2008;48(2):200-7. doi: 10.1016/j.jhep.2007.09.010.
Lewis DR, Chen HS, Cockburn MG, Wu XC, Stroup AM, Midthune DN, et al. Early estimates of SEER cancer incidence, 2014. Cancer. 2017;123(13):2524-34. doi: 10.1002/cncr.30630.
Goldberg DS, Fallon MB. The Art and Science of Diagnosing and Treating Lung and Heart Disease Secondary to Liver Disease. Clin Gastroenterol Hepatol. 2015;13(12):2118-27. doi: 10.1016/j.cgh.2015.04.024.
Yang TJ, Dhanasekar K, Bhandari R, Muraleedharan D, Chirindoth SS, Kaur H, et al. Association of Helicobacter Pylori With Development of Peptic Ulcer Disease Among Cirrhotic Patients: An Evidence From Population-Based Study. Cureus. 2021;13(11):e19315. doi: 10.7759/cureus.19315.
Kamalaporn P, Sobhonslidsuk A, Jatchavala J, Atisook K, Rattanasiri S, Pramoolsinsap C. Factors predisposing to peptic ulcer disease in asymptomatic cirrhotic patients. Aliment Pharmacol Ther. 2005;21(12):1459-65. doi: 10.1111/j.1365-2036.2005.02507.x.
Kirchner GI, Beil W, Bleck JS, Manns MP, Wagner S. Prevalence of Helicobacter pylori and occurrence of gastroduodenal lesions in patients with liver cirrhosis. Int J Clin Exp Med. 2011;4(1):26-31.
D’Amico G, De Franchis R; Cooperative Study Group. Upper digestive bleeding in cirrhosis. Post-therapeutic outcome and prognostic indicators. Hepatology. 2003;38(3):599-612. doi: 10.1053/jhep.2003.50385.
Chemych MD, Lyshnevska AH, Ivakhiv OL. [Chronic viral hepatitis in Ukraine. Peculiarities of their course. Problems]. In: Problems of infectious diseases in the practice of an internist: modern aspects: materials of the All-Ukrainian scientific and practical conference [Internet]; 2019 May 29-30; Sumy: Sumy State University; 2019 [cited 2023 May 12]; p. 141-5. Ukrainian. Available from: http://essuir.sumdu.edu.ua/handle/123456789/75221
Railian MV, Chumachenko TO, Makarova VI, Semishev VI. [Acute hepatitis of unknown etiology: the task of epidemiological surveillance in Ukraine in modern conditions]. Ukrainian Journal of Medicine, Biology and Sports. 2022;7(37):21-6. Ukrainian. doi: 10.26693/jmbs07.03.021.
Babinets LS. [Current provisions of the European (Finnish) clinical protocol for the management of patients with viral hepatitis in the practice of primary doctors and lecturers]. Modern gastroenterology. 2020;(6):52-9. Ukrainian. doi: 10.30978/MG-2020-6-52.
Cavalieri ML, D’Agostino D. Drug-, herband dietary supplement-induced liver injury. Arch Argent Pediatr. 2017;115(6):397-403. doi: 10.5546/ aap.2017.eng.e397.
Palmer M, Regev A, Lindor K, Avigan MI, Dimick-Santos L, Treem W, et al. Consensus guidelines: best practices for detection, assessment and management of suspected acute drug-induced liver injury occurring during clinical trials in adults with chronic cholestatic liver disease. Aliment Pharmacol Ther. 2020;51(1):90-109. doi: 10.1111/apt.15579.
Czigany Z, Tolba RH. New Frontiers in organ preservation and hepatoprotection. Int J Mol Sci. 2022;23(8):4379. doi: 10.3390/ijms23084379.
Hofmann J, Hackl V, Esser H, Meszaros AT, Fodor M, Öfner D, et al. Cell-Based Regeneration and Treatment of Liver Diseases. Int J Mol Sci. 2021;22(19):10276. doi: 10.3390/ijms221910276.
Miyajima A, Tanaka M, Itoh T. Stem/progenitor cells in liver development, homeostasis, regeneration, and reprogramming. Cell Stem Cell. 2014;14(5):561-74. doi: 10.1016/j.stem.2014.04.010.
Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663-76. doi: 10.1016/j.cell.2006.07.024.
Neshat SY, Quiroz VM, Wang Y, Tamayo S, Doloff JC. Liver Disease: Induction, Progression, Immunological Mechanisms, and Therapeutic Interventions. Int J Mol Sci. 2021;22(13):6777. doi: 10.3390/ijms22136777.
Shen LH, Fan L, Zhang Y, Zhu YK, Zong XL, Peng GN, et al. Protective Effect and Mechanism of Placenta Extract on Liver. Nutrients. 2022;14(23):5071. doi: 10.3390/nu14235071.
Holtsev AN, Yurchenko TN, editors. [Placenta: cryopreservation, clinical use]. Kharkiv: Brovyn AV; 2013. 268 p. Russian.
Pan SY, Chan MKS, Wong MBF, Klokol D, Chernykh V. Placental therapy: An insight to their biological and therapeutic properties. J Med Ther. 2017;1(3):1-6. doi: 10.15761/JMT.1000118.
Devarampati LJ, Koduganti RR, Savant S, Gullapelli P, Manchala S, Mydukuru A. Role of Placental Extracts in Periodontal Regeneration: A Literature Review. Cureus. 2022;14(6):e26042. doi: 10.7759/cureus.26042.
Takagi K, Okabe S, Saziki R. A new method for the production of chronic gastric ulcer in rats and the effect of several drugs on its healing. Jpn J Pharmacol. 1969;19(3):418-26. doi: 10.1254/jjp.19.418.
Shepitko KV. Application of cryopreserved placenta preparations in the small intestine pathologies in rats for their further use in exigent conditions. Bulletin of problems biology and medicine. 2019;19(4):56-61. doi: 10.29254/20774214-2019-4-2-154-56-61.
Repin MV, Marchenko LM, Govorukha TP, Vaskovich AM, Stroka VI, Kondakov II, et al. [Effect of preliminary introduction of placental cryoextracts of various origins on morphofuncional state of rats’ kidneys in acute renal failure]. Eksperymentalna ta klinichna medytsyna. 2017;(2):37-43. Ukrainian.
Hladkykh FV. Experimental study of the antiulcer effect of cryopreserved placenta extract on a model of acetylsalicylic acid-induced ulcerogenesis. Current Issues in Pharmacy and Medical Sciences. 2021;35(2):89-94. doi: 10.2478/cipms-2022-0017.
Hladkykh FV. Gastrocytoprotective properties of cryopreserved placenta extract in combined action of low temperatures and inhibition of cyclooxygenase. Acta Facultatis Medicae Naissensis. 2022;39(1):48-56. doi: 10.5937/afmnai39-33036.
Hladkykh FV, Chyzh MO. [Modulation of meloxicam-induced changes in gastrointestinal and motor activity of the stomach by applying placenta cryoextract]. Proc Shevchenko Sci Soc Med Sci. 2023;64(1):84-94. Ukrainian. doi: 10.25040/ntsh2021.01.08.
Hladkykh FV, Koshurba IV, Chyzh MO. [Characteristics of the antiulcerogenic activity of cryopreserved placenta extract in acute and chronic lesions of the stomach]. Modern Medical Technology. 2023;(1):62-8. Ukrainian. doi: 10.34287/MMT.1(56).2023.10.
Chyzh MO, Belochkina IV, Hladkykh FV. [Cryosurgery and physical medicine in treatment of cancer]. Ukrainian Journal of Radiology and Oncology. 2021;29(2):127-49. Ukrainian. doi: 10.46879/ukroj.2.2021.127-49.
Hladkykh FV. Anti-inflammatory properties of diclofenac sodium on the background of combined use with cryopreserved placenta extract in the experiment. Problems of cryobiology and cryomedicine. 2021;31(4):364-7. doi: 10.15407/cryo31.04.364.
Koshurba I, Hladkykh F, Chyzh M, Marchenko M, Belochkina I. [The characteristic of the gastric secretion after gastric cryodenervation and cryopreserved placenta extract administration]. Innov Biosyst Bioeng. 2023;7(1):42-51. Ukrainian. doi: 10.20535/ibb.2023.7.1.280183.
Hladkykh FV. The effect of meloxicam and cryopreserved placenta extract on initial inflammatory response an experimental study. Ceska Slov Farm. 2021;70(5):179-85. doi: 10.5817/CSF2021-5-179.
Chyzh MO, Koshurba IV, Marchenko MM, Hladkykh FV, Belochkina IV. [Gender determinism of the effect of placenta cryoextract on the hepatotropic effects of esomeprazole, clarithromycin and metronidazole in chronic liver damage]. Modern Medical Technology. 2023;(1):55-61. Ukrainian. doi: 10.34287/MMT.1(56).2023.9.
Koshurba IV, Chyzh MO, Hladkykh FV, Belochkina IV. [Influence of placenta cryoextract on the liver metabolic and functional state in Case of D-galactosamine hepatitis]. Innov Biosyst Bioeng. 2022;6(2):64-7. Ukrainian. doi: 10.20535/ibb.2022.6.2.264774.
Koshurba IV, Hladkykh FV, Chyzh MO, Belochkina IV, Rubleva TV. [Hepatotropic effects of triple antiulcer therapy and placenta cryoextract: the role of sex factors in lipoperoxidation]. Fiziologichnyi Zhurnal. 2022;68(5):25-32. Ukrainian. doi: 10.15407/fz68.05.025.
Koshurba IV. [Study of the effect of cryopreserved placenta extract on the processes of cytolysis and lipid peroxidation in ССl4-induced liver damage]. Modern Medical Technology. 2022;(3):46-54. Ukrainian. doi: 10.34287/ MMT.3(54).2022.9.
Hu C, Wu Z, Li L. Mesenchymal stromal cells promote liver regeneration through regulation of immune cells. Int J Biol Sci. 2020;16(5):893-903. doi: 10.7150/ijbs.39725.
Lou G, Chen Z, Zheng M, Liu Y. Mesenchymal stem cell-derived exosomes as a new therapeutic strategy for liver diseases. Exp Mol Med. 2017;49(6):e346. doi: 10.1038/emm.2017.63.
Li T, Yan Y, Wang B, Qian H, Zhang X, Shen L, et al. Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis. Stem Cells Dev. 2013;22(6):845-54. doi: 10.1089/scd.2012.0395.
Hu C, Wu Z, Li L. Pre-treatments enhance the therapeutic effects of mesenchymal stem cells in liver diseases. J Cell Mol Med. 2020;24(1):40-9. doi: 10.1111/jcmm.14788.
Berardis S, Dwisthi Sattwika P, Najimi M, Sokal EM. Use of mesenchymal stem cells to treat liver fibrosis: current situation and future prospects. World J Gastroenterol. 2015;21(3):742-58. doi: 10.3748/wjg.v21.i3.742.
Liu F, Endo Y, Romantseva T, Wu WW, Akue A, Shen RF, et al. T cell-derived soluble glycoprotein GPIbα mediates PGE2 production in human monocytes activated with the vaccine adjuvant MDP. Sci Signal. 2019;12(602):eaat6023. doi: 10.1126/scisignal.aat6023.
Bertoletti A, Ferrari C. Innate and adaptive immune responses in chronic hepatitis B virus infections: towards restoration of immune control of viral infection. Gut. 2012;61(12):1754-64. doi: 10.1136/gutjnl-2011-301073.
Moscoso CG, Steer CJ. The Evolution of Gene Therapy in the Treatment of Metabolic Liver Diseases. Genes (Basel). 2020;11(8):915. doi: 10.3390/ genes11080915.
Torres JL, Novo-Veleiro I, Manzanedo L, Alvela-Suárez L, Macías R, Laso FJ, et al. Role of microRNAs in alcohol-induced liver disorders and non-alcoholic fatty liver disease. World J Gastroenterol. 2018;24(36):4104-18. doi: 10.3748/wjg.v24.i36.4104.
Weber M, Mera P, Casas J, Salvador J, Rodríguez A, Alonso S, et al. Liver CPT1A gene therapy reduces diet-induced hepatic steatosis in mice and highlights potential lipid biomarkers for human NAFLD. FASEB J. 2020;34(9):11816-37. doi: 10.1096/fj.202000678R.
Logan GJ, de Alencastro G, Alexander IE, Yeoh GC. Exploiting the unique regenerative capacity of the liver to underpin cell and gene therapy strategies for genetic and acquired liver disease. Int J Biochem Cell Biol. 2014;56:14152. doi: 10.1016/j.biocel.2014.10.023.
Wan T, Zhong J, Pan Q, Zhou T, Ping Y, Liu X. Exosome-mediated delivery of Cas9 ribonucleoprotein complexes for tissue-specific gene therapy of liver diseases. Sci Adv. 2022;8(37):eabp9435. doi: 10.1126/sciadv.abp9435.
Villiger L, Grisch-Chan HM, Lindsay H, Ringnalda F, Pogliano CB, Allegri G, et al. Treatment of a metabolic liver disease by in vivo genome base editing in adult mice. Nat Med. 2018;24(10):1519-25. doi: 10.1038/ s41591-018-0209-1.
