Novosti
Khirurgii

 This journal is
indexed in Scopus
journal cover
android icon Android Applicaion

Year 2013 Vol. 21 No 3

REVIEWS

E.V. MAHILIAVETS, P.V. GARELIK, N.I. BATVINKOV

METHODS OF LIVER REGENERATION STIMULATION AT LIVER CIRRHOSIS

EE “Grodno State Medical University”
The Republic of Belarus

The article analyses the results of the applied methods of the liver regeneration stimulation in terminal stages of chronic diffuse diseases.
Among the concepts of the given therapy one considers the following: growth factors, drugs of similar action, cell therapy, activation of regeneration by the action of damaging factors. Intensive search of new pharmacological methods of liver regeneration stimulating having reflected in numerous scientific publications testifies about dissatisfaction of clinicians and researchers by the effectiveness of available resources. Stimulation resection techniques of the liver cirrhosis are invasive and often there is a risk of induction of the liver failure due to a reduction of liver parenchyma volume. For a cell therapy some problematic questions concerning the percentage of newly formed hepatocytes replacement of the hepatic parenchyma and the absence of morphological selectivity have remained.

Keywords: liver cirrhosis, reparative regeneration, growth factors, cell therapy
p. 103 – 109 of the original issue
References
  1. Garbuzenko DV. Mekhanizmy kompensatsii struktury i funktsii pecheni pri ee povrezhdenii i ikh prakticheskoe znachenie [Mechanisms of compensation of structure and function of the liver at its damage and their practical significance]. RZhGGK. 2008;18(6):14–21.
  2. Manuk'ian GV, Eramishantsev AK, Sukhikh GT, Markarian ASh. Vnutriorgannaia allotransplantatsiia stvolovykh i progenitornykh kletok pri lechenii bol'nykh tsirrozom pecheni i portal'noi gipertenziei [Intraorganic allotransplantation of stem and progenitor cells in the treatment of patients with cirrhosis and portal hypertension]. Annaly Khirurg Gepatologii. 2007;12(2):31–38.
  3. Sherlok Sh, Duli Dzh. Zabolevaniia pecheni i zhelchnykh putei [Diseases of the liver and biliary tract]: prakt ruk. Aprsina ZG, red. Moscow, RF: GEOTAR-Meditsina; 1999. 864 p.
  4. Xu B, Broome U, Uzunel M, Nava S, Ge X, Kumagai-Braesch M, Hultenby K, Christensson B, Ericzon BG, Holgersson J, Sumitran-Holgersson S. Capillarization of hepatic sinusoid by liver endothelial cell-reactive autoantibodies in patients with cirrhosis and chronic hepatitis. Am J Pathol. 2003 Oct;163(4):1275–89.
  5. Chijiiwa K, Nakano K, Kameoka N, Nagai E, Tanaka M. Proliferating cell nuclear antigen, plasma fibronectin, and liver regeneration rate after seventy percent hepatectomy in normal and cirrhotic rats. Surgery. 1994 Sep;116(3):544–49.
  6. Jeon SH, Chae BC, Kim HA, Seo GY, Seo DW, Chun GT, Kim NS, Yie SW, Byeon WH, Eom SH, Ha KS, Kim YM, Kim PH. Mechanisms underlying TGF-beta1-induced expression of VEGF and Flk-1 in mouse macrophages and their implications for angiogenesis. J Leukoc Biol. 2007 Feb;81(2):557–66.
  7. Shanmukhappa K, Sabla GE, Degen JL, Bezerra JA. Urokinase-type plasminogen activator supports liver repair independent of its cellular receptor. BMC Gastroenterol. 2006 Nov 29;6:40.
  8. Gaudio E, Pannarale L, Ripani M, Onori P, Riggio O. The hepatic microcirculation in experimental cirrhosis. A scanning electron microscopy study of microcorrosion casts. Scanning Microsc. 1991 Jun;5(2):495–502.
  9. Makhlouf MM, Awad A, Zakhari MM, Fouad M, Saleh WA. Vascular endothelial growth factor level in chronic liver diseases. J Egypt Soc Parasitol. 2002 Dec;32(3):907–21.
  10. Bortolotti F, Guido M. Reversal of liver cirrhosis: a desirable clinical outcome and its pathogenic background. J Pediatr Gastroenterol Nutr. 2007 Apr;44(4):401–6.
  11. Panin LE, Khoshchenko OM. Rol' rezidentnykh makrofagov v reguliatsii biosinteza DNK i belka v kletkakh astsitnoi gepatomy myshei linii A [A role of resident macrophages in the regulation of biosynthesis of DNA and protein in the cells of the mice ascitic hepatoma (line A)]. Vopr Onkologii. 2003;49(4):472–75.
  12. Gressner AM. Perisinusoidal lipocytes and fibrogenesis. Gut. 1994 Oct;35(10):1331–33.
  13. Kiiasov AP, Gumerova AA. Kletki Ito v ontogeneze i regeneratsii pecheni. [Ito cells in ontogeny and regeneration of the liver]. Tsitologiia. 2002;44(4):342–49.
  14. Martinez-Hernandez A, Amenta PS. The hepatic extracellular matrix. II. Ontogenesis, regeneration and cirrhosis. Virchows Arch A Pathol Anat Histopathol. 1993;423(2):77–84.
  15. Herbst H, Milani S, Heinrichs O, Schuppan D. Pathomorphology of acute and chronic stages of CCl4-induced liver fibrosis: immunohistochemical and in situ hybridization studies. Z Gastroenterol. 1992 Mar;30(Suppl 1):21–8.
  16. Soon RK Jr, Yee HF Jr. Stellate cell contraction: role, regulation, and potential therapeutic target. Clin Liver Dis. 2008 Nov;12(4):791–803.
  17. Zhang DW, Zhao YX, Wei D, Li YL, Zhang Y, Wu J, Xu J, Chen C, Tang H, Zhang W, Gong L, Han Y, Chen ZN, Bian H. HAb18G/CD147 promotes activation of hepatic stellate cells and is a target for antibody therapy of liver fibrosis. J Hepatol. 2012 Dec;57(6):1283–91.
  18. Khan AA, Parveen N, Mahaboob VS, Rajendraprasad A, Ravindraprakash HR, Venkateswarlu J, Rao SG, Narusu ML, Khaja MN, Pramila R, Habeeb A, Habibullah CM. Safety and efficacy of autologous bone marrow stem cell transplantation through hepatic artery for the treatment of chronic liver failure: a preliminary study. Transplant Proc. 2008 May;40(4):1140–44.
  19. Chernykh ER, Starostina NM, Paltsev AI, Leplina OY, Shevela EY, Shipunov MV, Selihova YB, Kulagin AD, Lisukov IA, Nikonov SD, Ostanin AA, Kozlov VA. Autologous bone marrow cells in the treatment of cirrhosis of the liver. Bull Exp Biol Med. 2007 Oct;144(4):640–45.
  20. Sakaida I, Terai S, Yamamoto N, Aoyama K, Ishikawa T, Nishina H, Okita K. Transplantation of bone marrow cells reduces CCl4-induced liver fibrosis in mice. Hepatology. 2004 Dec;40(6):1304–11.
  21. Piscaglia AC, Zocco MA, Di Campli C, Sparano L, Rutella S, Monego G, Bonanno G, Michetti F, Mancuso S, Pola P, Leone G, Gasbarrini G, Gasbarrini A. How does human stem cell therapy influence gene expression after liver injury? Microarray evaluation on a rat model. Dig Liver Dis. 2005 Dec;37(12):952–63.
  22. Yagi K, Kojima M, Oyagi S, Ikeda E, Hirose M, Isoda K, Kawase M, Kondoh M, Ohgushi H. Application of mesenchymal stem cells to liver regenerative medicine. Yakugaku Zasshi. 2008 Jan;128(1):3–9.
  23. Ueno T, Nakamura T, Torimura T, Sata M. Angiogenic cell therapy for hepatic fibrosis. Med Mol Morphol. 2006 Mar;39(1):16–21.
  24. Vyborova IS, Vasil'eva LS, Makarova NG. Gepatotropnye effekty rannei geterotransplantatsii embrional'noi tkani pecheni pri intoksikatsii etilenglikolem [Hepatotropic effects of early geterotransplantation of fetal liver tissue in ethylene glycol intoxication]. Sib Med Zhurn. 2007;72(5):22–24.
  25. Wu DC, Boyd AS, Wood KJ. Embryonic stem cell transplantation: potential applicability in cell replacement therapy and regenerative medicine. Front Biosci. 2007 May 1;12:4525–35.
  26. Lysy PA, Campard D, Smets F, Najimi M, Sokal EM. Stem cells for liver tissue repair: current knowledge and perspectives. World J Gastroenterol. 2008 Feb 14;14(6):864–75.
  27. Furnus CC, Inda AM, Andrini LB, Garcia MN, Garcia AL, Badran AF, Errecalde AL. Chronobiology of the proliferative events related to angiogenesis in mice liver regeneration after partial hepatectomy. Cell Biol Int. 2003;27(4):383–86.
  28. Garbuzenko DV, Bordunovskii VN, Revel'-Muroz ZhA, Guzhina AO, Kinzerskii AIu, Garbuzenko CB. Lazernaia transpechenochnaia revaskuliarizatsiia u bol'nykh tsirrozom pecheni s portal'noi gipertenziei [Transhepatic laser revascularization in patients with liver cirrhosis and portal hypertension]. Annaly Khirurg Gepatologii. 2002;7(1):279–80.
  29. Kovalenko VL, Abramovskaia NV, Garbuzenko DV. Morfologicheskaia kharakteristika kompensatorno-prisposobitel'nykh reaktsii v tsirroticheski izmenennoi pecheni posle vozdeistviia na nee vysokointensivnym lazernym izlucheniem [Morphological characteristics of the compensatory adaptive reactions in cirrhotic liver after high-intensity laser radiation]. Ural Med Zhurn. 2007;(12):75–78.
  30. Garelik PV. Diagnostika i lechenie zabolevanii pechenii zhelchnykh putei s pomoshch'iu laparoskopii [Diagnosis and treatment of liver and bile ducts by laparoscopy]. Zdravookhranenie Belorussii. 1990;(2):40–42.
  31. Reutov AA. Vliianie metabolicheski aktivnykh faktorov na vosstanovitel'nye protsessy v pecheni u zrelykh i starykh zhivotnykh s chastichnoi gepatektomiei [The influence of metabolically active factors on the regenerative processes in the liver of mature and old animals with partial hepatectomy]. Ros Fiziol Zhurn im IM Sechenova. 2004;90(8):451.
  32. Beliaev AN, Iniakin ON, Lapshin AE, Beliaev SA, Kechemaikin VN. Vliianie razlichnykh rezhimov vnutriportal'nogo vvedeniia infuzionnykh sred na morfofunktsional'noe sostoianie pecheni [Effect of different regimes of intraportal administration of infusion media on the morphology and function of the liver]. Gematologiia i Transfuziologiia. 2003;(2):32–35.
  33. Mizuno S, Nakamura T. Hepatocyte growth factor: a regenerative drug for acute hepatitis and liver cirrhosis. Regen Med. 2007 Mar;2(2):161–70.
  34. Conchillo M, Prieto J, Quiroga J. Insulin-like growth factor I (IGF-I) and liver cirrhosis. Rev Esp Enferm Dig. 2007 Mar;99(3):156–64.
  35. Xu H, Shi BM, Lu XF, Liang F, Jin X, Wu TH, Xu J. Vascular endothelial growth factor attenuates hepatic sinusoidal capillarization in thioacetamide-induced cirrhotic rats. World J Gastroenterol. 2008 Apr 21;14(15):2349–57.
  36. Smakhtin MIu, Konoplia AI, Shveinov IA. Stimuliatsiia reparativnoi regeneratsii faktorom rosta kletok pecheni i ego immunometabolicheskie effekty v usloviiakh gepatopatii, vyzvannoi gidrazinom [The stimulation of reparative regeneration by growth factor of liver cells and its immune metabolic effects in the conditions of hepatopathy caused by hydrazine]. Vestn Novykh Med Tekhnologii. 2003;(1-2):22–23.
  37. Sgrebneva MN, Tiupeleev PA, Khasina EI. Vliianie pektina zosterina na metabolizm v pecheni v usloviiakh svintsovoi intoksikatsii [Effect of pectin zosterin on metabolism in the liver at lead intoxication]. Mikroelementy v Meditsine. 2004;5(Vyp 4):124–26.
  38. Ozdogan M, Ersoy E, Dundar K, Albayrak L, Devay S, Gundogdu H. Beneficial effect of hyperbaric oxygenation on liver regeneration in cirrhosis. J Surg Res. 2005 Dec;129(2):260–4.
  39. Kurbangulov IB, Nartailakov MA, Muldashev ER, Mingazov PC, Muslimov SA, Safin IA, Musina LA. Khirurgicheskoe lechenie khronicheskogo gepatita i tsirroza pecheni [Surgical treatment of chronic hepatitis and cirrhosis of the liver]. Annaly Khirurg Gepatologii. 2005;10(2):13–20.
  40. Ishikawa T, Terai S, Urata Y, Marumoto Y, Aoyama K, Murata T, Mizunaga Y, Yamamoto N, Nishina H, Shinoda K, Sakaida I. Administration of fibroblast growth factor 2 in combination with bone marrow transplantation synergistically improves carbon-tetrachloride-induced liver fibrosis in mice. Cell Tissue Res. 2007 Mar;327(3):463–70.
  41. Kriuk AS, Mostovnikov VA, Khokhlov IV, Serdiuchenko NS. Terapevticheskaia effektivnost' nizkointensivnogo lazernogo izlucheniia [The therapeutic efficacy of low-intensity laser radiation]. Minsk, RB; 1986. 231 p.
  42. Veremeichik AP, Davydova VV, Butvilovskii VE, Gaiduk VS. Morfologicheskie izmeneniia kozhi morskikh svinok pri allergicheskom kontaktnom dermatite i ego lechenii nizkointensivnym lazernym izmeneniem [Morphological changes in the skin of guinea pigs with allergic contact dermatitis and treatment by low-intensity laser]. Belorus Med Zhurn. 2003;(3):51–54.
  43. Pavliust LP. Obshchie lipidy, kholesterin, triglitseridy v plazme krovi pri vozdeistvii nizkointensivnogo lazernogo izlucheniia [The general lipids, cholesterol, triglycerides in plasma under exposion by low-intensity laser radiation]. Problemy Patologii v Eksperimente i Klinike. 1987;9:142–43.
  44. Araslanov SA. Vliianie lazernogo izlucheniia i krasnogo sveta na soderzhanie kollagena v regeneriruiushchei pecheni krys [Effect of laser radiation and red light on the collagen content of the rat regenerative liver]. Aktual Problemy Meditsiny i Farmatsii. Kursk, RF; 1998. p. 31–2.
  45. Ivushkin SA, Aleksandrov MT. Sposob lecheniia khronicheskogo gepatita. Novye dostizheniia lazernoi meditsiny [Method of treatment of chronic hepatitis. New achievements of laser medicine]. Sb tez mezhdunar konf. Moscow, RF; 1993. p. 81.
  46. Serebrovskaia LV, Makashova VV, Solntseva VN, Omarova KhG. Vozdeistvie nizkointensivnogo lazernogo izlucheniia na kliniko-immunologicheskie pokazateli bol'nykh ostrym virusnym gepatitom B [The impact of low-intensity laser radiation on clinical and immunological parameters in patients with acute viral hepatitis B]. V. Epidemiologiia i Infekts Bolezni. 1999;(3):41–44.
Address for correspondence:
230023 Respublika Belarus' g. Grodno, ul. Gor'kogo, d. 80, UO "Grodnenskii gosudarstvennyi meditsinskii universitet", kafedroi obshchei khirurgii,
e-mail: emogilevec@yandex.ru,
Mahiliavets Eduard Vladislavovich
Information about the authors:
Mahiliavets E.V. PhD, an associate professor of the 1st chair of surgical diseases of EE “Grodno State Medical University”.
Garelik P.V. MD, a head of the general surgery chair of EE “Grodno State Medical University”.
Batvinkov N.I. MD, a head of the 1st chair of surgical diseases of EE “Grodno State Medical University”.
Contacts | ©Vitebsk State Medical University, 2007-2023