1. Moscow state medical- dentistry University n. a. A.I. Evdokimov (Moscow, Russian Federation)
2. North-Western State Medical University n. a. I.I. Mechnikov (Saint Petersburg, Russian Federation)

Keywords: fibrosis, liver, Laennec, collagen matrix, NASH

Abstract: LAENNEC: It is a multicomponent preparation based on Human placental hydrolysate, which has a proliferative effect on hepatocytes and fibrinolytic — on the connective tissue. This study proves fibrinolytic effect of drug “Laennec” in patients with nonalcoholic steatohepatitis during 4 months of monotherapy. This drug able to normalize marker of inflammation, cytolysis and cholestasis. Also it improves protein synthesis and the activity of antioxidant which leads to decrease in right hypochondrium pain, asthenic syndrome, manifestations of hepatic insufficiency and severity of fibrosis in liver.

• References total 68 ⇓ :: .
  1. Gromova O.A. Torshchin I.Yu., Volkov A.Yu., Smarygin S.N., Nazarenko O.A., Karimova I.M. Preparat Laennek: elementnyi sostav i farmakologicheskoe deistvie. Plasticheskaya khirurgiya i kosmetologiya. 2011:2:327-333.
  2. Lazebnik L.B., Radchenko V.G., Golovanova E.V., Zvenigorodskaya L. A. Nealkogol'naya zhirovaya bolezn' pecheni: klinika, diagnostika, lechenie (rekomendatsii dlya terapevtov, 2-versiya). Eksperimental'naya i klinicheskaya gastroenterologiya – Experimental and Clinical Gastroenterology Journal. 2017;138(2):22-37.
  3. Maksimov V.A., Minushkin O.N., Pal'tsev A.I., Saifutdinov R.G., Chernyshev A.L., Gromova R.A., Gusakova E.V., Radchenko V.G., Lazebnik L.B. Rekomendatsii po primeneniyu gidrolizata chelovecheskoi platsenty pri zabolevaniyakh pecheni. Eksperimental'naya i klinicheskaya gastroenterologiya – Experimental and Clinical Gastroenterology Journal. 2016;136(12):75-77.
  4. Мinushkin O.N., Dibrova E.A., Karimova I.Ya., et al. «Laennek» – novyi gepatoprotektivnyi preparat dlya lecheniya steatogepatitov razlichnoi etiologii». Kremlevskaya meditsina. 2007;2:65-67.
  5. Minushkin O.N., Leont'ev S.I., Maslovskii L.V., et al. Primenenie diskriminantnoi schetnoi shkaly dlya otsenki fibroobrazovaniya v pecheni u bol'nykh s khronicheskimi gepatitami. Gepatologiya. 2005;1:16-24.
  6. Pavlov Ch.S., Zolotarevskii V.B., Tomkevich M.S. Vozmozhnosti obratimosti tsirroza pecheni. Rossiiskii zhurnal Gastroenterologii, Gepatologii, Koloproktologii – The Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2006;1:20-29.
  7. Pavlov Ch.S., Ivashkin V.T. Biopsiya pecheni: metodologiya i praktika segodnya. Rossiiskii zhurnal Gastroenterologii, Gepatologii, Koloproktologii – The Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2006;16(4):65-78.
  8. Pavlov Ch.S., Glushenkov D.V., Ivashkin V.T. Sovremennye vozmozhnosti elastometrii fibro- i akti-testa v diagnostike fibroza pecheni. Rossiiskii zhurnal Gastroenterologii, Gepatologii, Koloproktologii – The Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2008;4:43-52.
  9. Pavlov Ch.S., Zolotarevskii V.B., Tomkevich M.S. Vozmozhnosti obratimosti tsirroza pecheni. Rossiiskii zhurn al Gastroenterologii, Gepatologii, Koloproktologii – The Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2006;1:20-29.
  10. Radchenko V.G., Seliverstov P.V., Ivanova V.F., Sitkin S.I. Algoritm lecheniya nealkogol'noi zhirovoi bolezni pecheni i rol' mitokhondrial'noi disfunktsii v ee razvitii. Фарматека. 2017;6:12-19.
  11. Radchenko V.G., Seliverstov P.V. Vozrastnye izmeneniya pecheni. Vestnik SZGMU im. I.I. Mechnikova. 2017;9(1):110-116.
  12. Seliverstov P.V., Radchenko V.G. Rol' mitokhondrial'noi tsitopatii pri steatoze u bol'nykh nealkogol'noi zhirovoi bolezn'yu pecheni. Effektivnaya farmakoterapiya. 2017;5:16-24.
  13. Severov M.V. Obratimost' fibroza i tsirroza pecheni pri HCV–infektsii. Gepatologicheskii forum. 2008;1:2-6.
  14. Storozhakov G.I., Ivkova A.N. Patogeneticheskie aspekty fibrogeneza pri khronicheskikh zabolevaniyakh pecheni. Klinicheskie perspektivy gastroenterologii, gepatologii. 2009;2:3-10.
  15. Sherlok Sh., Duli Dzh. Zabolevaniya pecheni i zhelchnykh putei. Prakticheskoe rukovodstvo. Мoscow, GEOTAR-MED, 2002. 864 p.
  16. Albanis E., Friedman S.L. Hepatic fibrosis. Pathogenesis and principles of therapy. Clin. Liver Dis. 2001;5:315-334.
  17. Arthur M.J. Fibrogenesis II. Metalloproteinases and their inhibitors in liver fibrosis. American Journal of Physiology, Gastrointestinal and Liver Physiology. 2000;279:G245-G249.
  18. Arthur M.J. Reversibility of liver fibrosis and cirrhosis following treatment for hepatitis C. Gastroenterology. 2002;122:1525-1528.
  19. Asrani S.K., Talwalkar J.A., Kamath P.S., Shah V.H., Saracino G., Jennings L., et al. Role of magnetic resonance elastography in compensated and decompensated liver disease. J Hepatol. 2014;60:934-939.
  20. Bataller R., Brenner D.A. Liver fibrosis. The Journal of Clinical Investigation. 2005;115:209-218.
  21. Bataller R. Genetic polymorphisms and the progression of liver fibrosis: a critical appraisal / R. Bataller, K. E. North, D. A. Brenner // Hepatology. - 2003. - No. 37. - Р. 493-503.
  22. Bataller R. Genetic polymorphisms and the progression of liver fibrosis: a critical appraisal / R. Bataller, K. E. North, D. A. Brenner // Hepatology. - 2003. - No. 37. - Р. 493-503.
  23. Bataller R. et al. Angiotensin II induces contraction and proliferation of human hepatic stellate cells / R. Bataller et al. // Gastroenterology. - 2000. - No. 118. - Р. 1149-1156.
  24. Bataller R. et al. Prolonged infusion of angiotensin II into normal rats induces stellate cell activation and proinflammatory events in liver /R. Bataller et al. // Am. J. Physiol. Gastrointest. Liver Physiol. - 2003. - No. 285. - P. G642-G651.
  25. Bataller R. et al. NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis / Bataller R. et al. // J. Clin. Invest. - 2003. - No. 112. - Р. 1383-1394.
  26. Benyon R. C. Is liver fibrosis reversible? / R. C. Benyon, J. P. Iredale // Gut. - 2000. - No. 46. - Р. 443-446.
  27. Brunt E. M. Nonalcoholic steatohepatitis / E. M. Brunt // Semin. Liver Dis. - 2004. - No. 24. - Р. 3-2.
  28. Brun P. Exposure to bacterial cell wall products triggers an inflammatory phenotype in hepatic stellate cells / P. Brun, I. Castagliuolo, M. Pinzani, G. Palu, D. Martines // Am J Physiol Gastrointest Liver Physiol. - 2005. - Vol. 289, No. 3. - P. G571-G578.
  29. Cadranel J. Practices of liver biopsy in France: results of a prospective nationwide survey. For the Group of Epidemiology of the French Association for the Study of the Liver (AFEF) / J. Cadranel, P. Rufat, F. Degos // Hepatology. - 2000. - No 32. - P. 477-81.
  30. Canbay A. et al. Fas enhances fibrogenesis in the bile ductligated mouse: a link between apoptosis and fibrosis / A. Canbay et al. // Gastroenterology. - 2002. - No. 123. - Р. 1323-1330.
  31. Chen Y., et al. Hedgehog controls hepatic stellate cell fate by regulating metabolism / Y. Chen, S. S. Choi, G. A. Michelotti, I. S. Chan, M. Swiderska-Syn, G. F. Karaca, et al. // Gastroenterology. - 2012. -Vol. 143. - P. 1319-1329.
  32. De Alwis N. M. W. Non-alcoholic fatty liver: the mist gradually clear / N.M.W. De Alwis, C. P. Day // J Hepatol. - 2008. - No. 48. - P. S 105-S 112.
  33. Diego Garcia-Compean. Liver cirrhosis and diabetes: Risk factors, pathophysiology, clinical implications and management / Diego Garcia-Compean, Joel Omar Jaquez-Quintana, Jose Alberto Gonzalez-Gonzalez, Hector Maldonado-Garza// World J Gastroentrol. -2009. - Vol. 15. - No. 3. - P. 280-288.
  34. Gabele E. Liver fibrosis: signals leading to the amplification of the fibrogenic hepatic stellate cell / E. Gabele, D. A. Brenner, R. A. Rippe // Front. Biosci. - 2003. - No. 8. - D 69-D 77.
  35. Gilmore I. et al. Indications, methods, and outcomes of percutaneous liver biopsy in England and Wales / I. Gilmore, A. Burroughs, I. Murray-Lyon, et al. // An audit by the British Society of Gastroenterology and the Royal College of Physicians of London. Gut. - 1995. -No. 36. - P. 437-41.
  36. Gressner A. M. Roles of TGF_beta in hepatic fibrosis / A. M. Gressner, R. Weiskirchen, K. Breitkopf, S. Dooley // Front. Biosci. - 2002. -No.7. - P. d793-d807.
  37. Ishak K. et al. Histological grading and staging of chronic hepatitis / K. Ishak, A. Baptista, L. Bianchi, et al. J. Hepatol. - 1995. - No. 2. - P. 696-99.
  38. Iredale J. P. Models of liver fibrosis: exploring the dynamic nature of inflammation and repair in a solid organ / J. P. Iredale // J. Clin. Invest. - 2007. - Vol. 117, No. 3. - P. 539-548.
  39. Issa R. et al. Spontaneous recovery from micronodular cirrhosis: evidence for incomplete resolution associated with matrix crosslinking / R. Issa et al. // Gastroenterology. - 2004. - No. 126. - Р. 1795-1808.
  40. Kamada Y. et al. Enhanced carbon tetrachloride induced liver fibrosis in mice lacking adiponectin / Y. Kamada et al. // Gastroenterology. -2003. - No. 125. - Р. 1796-1807.
  41. Kanno K., Tazuma S., Chayama K. AT1A-deficient mice show less severe progression of liver fibrosis induced by CCl (4) / K. Kanno, S. Tazuma, K. Chayama // Biochem. Biophys. Res. Commun. - 2003. - No. 308. - Р. 177-183.
  42. Kinnman N. Peribiliary myofibroblasts in biliarytype liver fibrosis / N. Kinnman, C. Housset // Front. Biosci. - 2002. - No. 7. - Р. 496-503.
  43. Knodell R., et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis / R. Knodell, K. Ishak, W. Black, et al. // Hepatology. - 1981. - No. 4. -P.431-35.
  44. Lee Y. A., Wallace M. C., Friedman S. L. Pathobiology of liver fibrosis: a translational success story / Y. A. Lee, M. C. Wallace, S. L. Friedman // Gut. - 2015. - No. 64. - P. 830-41. doi: 10.1136/gutjnl-2014-306842.
  45. Macias-Barragan J. Update on the pathophysiology of liver fibrosis. / J. Macias-Barragan // Expert Rev Gastroenterol Hepatol. - 2010. - Vol. 4. - P. 459-472.
  46. Marra F. Chemokines in liver inflammation and fibrosis / F. Marra // Front. Biosci. - 2002. - No. 7. - P. 1899-1914.
  47. Mann D. A. Epigenetics in liver disease / D. A. Mann // Hepatology. - 2014. - Vol. 60. - P. 1418-1425.
  48. Magness S. T. A dual reporter gene transgenic mouse demonstrates heterognity in hepatic fibrogenic cell populations / S. T. Magness, R. Bataller, L. Yang, D. A. Brenner // Hepatology. - 2004. -No. 40. - Р. 1151-1159.
  49. Novo E. Redox mechanisms in hepatic chronic wound healing and fibrogenesis / E. Novo, M. Parola // Fibrogenesis Tissue Repair. - 2008. - P. 1-5.
  50. Novo E., et al. Vascular endothelial growth factor and angiopoietin-1 as hypoxia-dependent autocrine and paracrine factors stimulating migration and chemotaxis of activated human hepatic stellate cells / E. Novo, S. Cannito, E. Zamara, L. Valfre di Bonzo, A. Caligiuri, C. Cravanzola, et al. // Am J Pathol. - 2007. - Vol. 170. - P. 1942-1953.
  51. Oben J. A. et al. Hepatic fibrogenesis requires sympathetic neurotransmitters / J. A. Oben et al. // Gut. - 2004. - No. 53. - Р. 438-445.
  52. Ogawa E. et al. The longitudinal quantitative assessment by transient elastography of chronic hepatitis C patients treated with with pegylated interferon alpha-2d and ribavirin / E. Ogawa, N. Furusyo, K. Toyoda, et al. // Antiviral Res. - 2009. - Vol. 83, Issue-2. - P. 127-34.
  53. Olsen A. L., et al. Hepatic stellate cells require a stiff environment for myofibroblastic differentiation / A. L. Olsen, S. A. Bloomer, E. P. Chan, M. D. Gaca, P. C. Georges, B. Sackey, et al. // Am J Physiol Gastrointest Liver Physiol. - 2011. - Vol. 301. - P. G110-G118.
  54. Parsons C. J. Molecular mechanisms of hepatic fibrogenesis / C. J. Parsons, M. Takashima, R. A. Rippe // J Gastroenterol Hepatol. - 2007. - Vol. 22, No. 1. - P. 79-84.
  55. Pellicoro A. Liver fibrosis and repair: immune regulation of wound healing in a solid organ / A. Pellicoro, P. Ramachandran, J. P. Iredale, J. A. Fallowfield // Nat Rev Immunol. - 2014. - No.14- P. 181-194.
  56. Safadi R. et al. Immune stimulation of hepatic fibrogenesis by CD 8 cells and attenuation by transgenic interleukin_10 from hepatocytes / R. Safadi et al. // Gastroenterology. - 2004. - No. 127. - Р. 870-882.
  57. Sahai A. et al. Upregulation ofosteopontin expression is involved in the development of nonalcoholic steatohepatitis in a dietary murine model / A. Sahai, P. Malladi, H. Melin_Aldana // Am. J. Physiol.Gastrointest. Liver Physiol. - 2004. - No. 287. - Р. G264-G273.
  58. Sato M. Hepatic stellate cells: unique characteristics in cell biology and phenotype / M. Sato, S. Suzuki, H. Senoo // Cell Struct. Funct. - 2003. - No. 28. - Р. 105-112.
  59. Schwabe R. F. Human hepatic stellate cells express CCR 5 and RANTES to induce proliferation and migration / R. F. Schwabe, R. Bataller, D. A. Brenner // Am. J. Physiol. Gastrointest. Liver Physiol. - 2003. - No. 285. - P. G949-G958.
  60. Schnabl B. Interactions between the intestinal microbiome and liver diseases/ B. Schnabl, D. A. Brenner // Gastroenterology. -2014. - Vol. 146. - P. 1513-1524.
  61. Shek F. W. How can transforming growth factor beta be targeted usefully to combat liver fibrosis? / F. W. Shek, R. C. Benyon // Eur. J. Gastroenterol. Hepatol. - 2004. - No. 16. - Р. 123-126.
  62. Streetz K. L. et al. Interleukin 6/gp130-dependent pathways are protective during chronic liver diseases / K. L. Streetz et al. // Hepatology. - 2003. - No. 38. - Р. 218-229.
  63. Takehara T. et al. Hepatocyte_specific disruption of BclxLleads to continuous hepatocyte apoptosis and liver fibrotic responses / T. Takehara et al. // Gastroenterology. - 2004. - No. 127. - Р. 1189-1197.
  64. Ueberham E. et al. Conditional tetracycline regulated expression of TGF_beta1 in liver of transgenic mice leads to reversible intermediary fibrosis / E. Ueberham et al. // Hepatology. - 2003. - No. 37. - Р. 1067-1078.
  65. Wang H. Effect of acid-sensing ion channel 1a on the process of liver fibrosis under hyperglycemia / H. Wang, Y. H. Wang, F. Yang, X. F. Li // Biochemical and Biophysical Research Communications. - 2015. - Vol. 468. - No. 4. - P. 758-765. www.doi.org/10.1016/j.bbrc.2015.11.029
  66. Yoshida T. et al. SOCS 1 is a suppressor of liver fibrosis and hepatitis_induced carcinogenesis / T. Yoshida et al. // J. Exp. Med. - 2004. - No. 199. - Р.1701-1707.
  67. Yoshiji H. et al. Tissue inhibitor of metalloproteinases-1 attenuates spontaneous liver fibrosis resolution in the transgenicmouse / H. Yoshiji et al. // Hepatology. - 2002. - No. 36. - Р. 850-860.
  68. Yu C. et al. Role of fibroblast growth factor type 1 and 2 in carbon tetrachloride_induced hepatic injury and fibrogenesis / C. Yu et al. // Am. J. Pathol. - 2003. - No. 163. - Р. 1653-1662.

Full text is published :
Lazebnik L.B., Radchenko V.G., Seliverstov P.V., Sitkin S.I. et al. THE CONTEMPORARY UNDERSTANDING OF LIVER FIBROSIS AND APPROACHES TO TREATMENT IN PATIENTS WITH NONALCOHOLIC STEATOHEPATITIS. Experimental and Clinical Gastroenterology Journal. 2017;148(12):98-108
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