ISSN 2415-3060 (print), ISSN 2522-4972 (online)
  • 7 of 44
Up
УЖМБС 2019, 4(2): 45–50
https://doi.org/10.26693/jmbs04.02.045
Medicine. Reviews

Changes in the Structure of the Liver during Obesity (Literature Review)

Prymachenko V. I.
Abstract

The article analyses scientific literature on the actual problem of medical science of the present concerning study and analysis of structural and functional changes in the liver during obesity. One of the most common chronic liver diseases in the modern world is non-alcoholic fatty liver disease which becomes a pandemic on the background of obesity. Data of researches of domestic and foreign scientists about non-alcoholic fatty liver disease represent important evidence of significant structural changes in the liver at different levels of organ organization (organ, tissue, cell, and molecule). The results of scientists` researches point at the fact that 75% of patients with obesity have non-alcoholic fatty liver disease. Almost all the patients have non-alcoholic fatty liver disease during the morbid obesity which is one of the most common liver diseases all over the world and gets the status of the pandemic one nowadays. Pathogenetic mechanisms of non-alcoholic fatty liver disease development are complicate enough and still are the question for scientists to be discussed. Non-alcoholic fatty liver disease is the main hepatic demonstration of the metabolic syndrome and has close connection to the obesity and to the insulin resistance. Obesity leads to changes in the structural organization of the liver which affect on its functional state and metabolic processes. Non-alcoholic fatty liver disease combines several pathological statuses, fatty steatosis or fatty liver dystrophy which has mostly benign character, non-alcoholic steatohepatitis, which is characterized with the progress to the liver fibrosis, and then to the liver cirrhosis, moreover cirrhosis passes into the hepatocellular carcinoma. Many researchers are trying to find the pathological, genetic and morphological features of non-alcoholic liver steatosis and non-alcoholic steatohepatitis during obesity. They are two morphological features or stages of disease: steatosis and steatohepatitis are mentioned in the International Statistical Classification of Diseases and Related Health Problems. Morphologists are still using such terms as "fatty liver dystrophy", "fatty liver", "fatty liver degeneration" and other ones in order to determine two possible forms as stages of disease: steatosis and steatohepatitis. Fatty liver disease is characterized with the fatty scurf in the liver, which leads to the failure of the normal development of hepatocytes. Healthy cells are replaced by the products of the fat exchange (metabolism) and the liver stops its biological functioning. This stage is called liver steatosis and is characterized by the fatty dystrophy of the liver cells. Liver steatosis is the histological indication of non-alcoholic fatty liver disease, development of which one is characterized with the insulin resistance, hyperinsulinism and increased quantity of the liberal fatty acids. The high concentrations of the liberal fatty acids in conditions of the insulin resistance are the main mechanism of forming the steatosis among people with non-alcoholic fatty liver disease. This regularity is confirmed by the results of the clinic and laboratory researches. Accumulation of the certain percent of lipids in the liver cells leads to the appearance of the second stage of the fatty disease – steatohepatitis, which is characterized with the inflammatory processes in the liver and with the necrosis or hepatocytes. The professional literature mentions that investigating the liver biopsy in the conditions of experimental model of non-alcoholic fatty liver disease we can indicate the apoptosis of hepatocytes and expressive changes of the structure and form of hepatocytes (phenomenon of polymorphism). The following factors can cause appearance of the steatohepatitis and non-alcoholic fatty liver disease: obesity, endogenous disorders of the lipid and carbohydrate metabolism, metabolic failures, the syndrome of malabsorption, medication use etc. The third (the last) stage is characterized with the replacing of the liver cells by cells of the connective tissue. Respectively, we can watch the development of fibrosis and later - cirrhosis, so the liver loses its main functions. In the professional editions researchers point at the fact that non-alcoholic fatty liver disease appeared due to the bacterial growth in the small intestine. Oxidative liver stress could depend not only on the high concentration of circulating liberal fatty acids during obesity, but also on the high concentration of endotoxins on the background of disbiotic violations being characteristic features of the syndrome of enormous bacterial growth. Increasing the amount of circulating endotoxins in the portal blood activates the liver Kupfer's cells which lead to the appearance of anti-inflammatory cytokines and chemokines which are the substrate of the inflammatory component of steatosis transformation during non-alcoholic steatohepatitis and induction of fibrogenesis. The study of pathogenetic mechanisms for the development of non-alcoholic fatty liver disease, the classification of risk facts, criteria of diagnosis, estimation of the prognosis of the course of the disease are important for the search and substantiation of effective methods of prevention and treatment.

Keywords: obesity, non-alcoholic fatty liver disease, steatosis, metabolic syndrome, fatty dystrophy

Full text: PDF (Ua) 178K

References
  1. Bentsa TM. Non-alcoholic fatty liver disease in patients with diabetes mellitus type 2 and obesity: diagnostics and treatment. Lection, reviews, news. Liky Ukrainy [Medicine of Ukraine]. 2016; 3(28): 8-12. [Ukrainian]
  2. Vasendin DV. Structural and functional changes in the liver with obesity (literature review). Scholarly notes of Petrozavodsky state university. Meditsinskiye nauki [Medical sciences]. 2014; 2(8): 57-62. [Russian]
  3. Vasendin DV, Michurina SV, Ishchenko IY. Morphometrical research of liver of rats Vistar with alimentary obesity model. Uchenyye zapiski Sankt-Peterburgskogo gosudarstvennogo medicinskogo universiteta im akad IP Pavlova [Scharly notes of StPetersburg state medicql university after academician IP Pavlov]. 2014; XXI(1): 41–4. [Russian]
  4. Harapko TV. Morphological features of components of tissues and organs in obesity. Messenger of biological and medical problems. 2018; 2(143): 12-6. [Ukrainian]
  5. Drapkina OM. Epidemological features of non-alcoholic fatty liver disease in Russia. Results of the open, multicentral prospective research - observation DIREG. RZhGGK. 2014; 24(4): 32-38. [Russian]
  6. Ivashkin VT, Drapkina OM, Mayev IV, et al. Prevalance of non - alcoholic fatty liver disease among people of outpatient and polyclinical practice in the Russian Federation: results of research DIREG 2. Hepatology RZhGGK. 2015; 6: 31-41. [Russian]
  7. Komshilova KA, Troshina EA. Obesity and non-alcoholic fatty liver disease. Lecheniye i profilaktika [Treatment and prevention]. 2012; 1: 99-108. [Russian]
  8. Larin AS, Tkach SM. Pethogenetical role of intestinal dysbiosis in development of obesity, insulin resistance and diabetes type 2. Zdorovya Ukrainy [Health of Ukraine]. 2016; 2(40): 20–1. [Ukrainian]
  9. Livzan MA, Krolovets TS, Lapteva IV, Cherkashchenko NA. Non-alcoholic fatty liver disease in the patients presenting with abdominal obesity. Dokazatel'naya gastroenterologia [Evidence gadtroenterology]. 2014; 4: 8-14. [Russian]
  10. Mayev IV, Andreyev DN, Dicheva DT, Kuznetsova YI. Non-alcoholic fatty liver disease: manual for doctors. M: Prima Print Publ; 2017. 64 p. [Russian]
  11. Martyniuk GV, Skoreiko NT, Skoreiko RS, Skoreiko SS. Metabolic syndrome - some features of pathogenesis its impact on development of arterial hypertension. Bukovinski medychnyi visnyk [Bukovynsky medical messenger]. 2016; 2(78): 85-7. [Ukrainian]
  12. Seliverstov PV, Radchenko VG. Non-alcoholic fatty liver disease, new opportunities of therapy. Medicinskii almanakh [Medical almanac]. 2014; 1: 38-40. [Ukrainian]
  13. Seliverstov PV. Non- alcoholic fatty disease of liver: from theory to practise. Archiv vnutrennei medicini [Archive of internal medicine]. 2015; 1(21): 19-26. [Ukrainian]
  14. Stepanov UM, Gaidar UA. Steatosis Histopathology. Steatohepatitis during diffusive liver diseases. Clinical medicine. Zhurnal NAMN Ukrainy [NAMN Ukrainian magazine]. 2015; 21(2): 235-40. [Ukrainian]
  15. Tkach SM, Tymoshenko OS, Dorofeyeva AA. Involment of gut microbiota in the development of obesity and insulin resistance. Klinichna endocrinologiya ta endokrinna chirurgiya [Clinical endocrinology and endocrine surgery]. 2016; 1(53): 7-16. [Ukrainian]
  16. Truhan DI. Non-alcoholic fatty liver disease, associated with obesity: opportunities of essential phospholipides. Medicinskii Sovet [Medical council]. 2016; 4: 116-22. [Russian]
  17. Abu-Shanab A, Quigley EM. The role of the gut microbiota in nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol. 2010; 7(12): 691-701. https://www.ncbi.nlm.nih.gov/pubmed/21045794. https://doi.org/10.1038/nrgastro.2010.172
  18. Ahmed M. Non-alcoholic fatty liver disease in 2015. World J Hepatol. 2015; 7(11): 1450-9. https://www.ncbi.nlm.nih.gov/pubmed/26085906. https://www.ncbi.nlm.nih.gov/pmc/articles/4462685. https://doi.org/10.4254/wjh.v7.i11.1450
  19. Buzzetti E, Pinzani M, Tsochatzis EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism. 2016; 65(8): 1038-48. https://www.ncbi.nlm.nih.gov/pubmed/26823198. https://doi.org/10.1016/j.metabol.2015.12.012
  20. Castro AV, Kolka CM, Kim SP, Bergman RN. Obesity, insulin resistance and comorbidities? Mechanisms of association. Arq Bras Endocrinol Metabol. 2014; 58(6): 600-9. https://www.ncbi.nlm.nih.gov/pubmed/25211442. https://www.ncbi.nlm.nih.gov/pmc/articles/4423826
  21. Chitturi S, Abeygunasekera S, Farrell GC, Holmes-Walker J, Hui JM, Fung C, et al. NASH and insulin resistance: Insulin hypersecretion and specifi c association with the insulin resistance syndrome. Hepatology. 2002; 35: 373-9. https://www.ncbi.nlm.nih.gov/pubmed/11826411. https://doi.org/10.1053/jhep.2002.30692
  22. International Statistical Classification of Diseases and Related Health Problems 10th Revision. Geneva: WHO; 1995. Available from: https://www.who.int/classifications/icd/ICD10Volume2_en_2008.pdf
  23. Ilan Y. Leaky gut and the liver: a role for bacterial translocation in nonalcoholic steatohepatitis. World J Gastroenterol. 2012; 18(21): 2609-18. https://www.ncbi.nlm.nih.gov/pubmed/22690069. https://www.ncbi.nlm.nih.gov/pmc/articles/3369997. https://doi.org/10.3748/wjg.v18.i21.2609
  24. Mishra A, Younossi ZM. Epidemiology and natural history of nonalcoholic fatty liver disease. J Clin Exp Hepatology. 2012; 2(2): 135-44. https://www.ncbi.nlm.nih.gov/pubmed/25755422. https://www.ncbi.nlm.nih.gov/pmc/articles/3940561. https://doi.org/10.1016/S0973-6883(12)60102-9
  25. Review Team, LaBrecque DR, Abbas Z, Anania F, Ferenci P, Khan AG, et al. World Gastroenterology Organisation Global Guidelines. Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis. J Clin Gastroenterol. 2014 Jul; 48(6): 467-73. https://www.ncbi.nlm.nih.gov/pubmed/24921212. https://doi.org/10.1097/MCG.0000000000000116
  26. Oh H, Jun DW, Saeed WK, Nguyen MH. Non-alcoholic fatty liver diseases: update on the challenge of diagnosis and treatment. Clin Mol Hepatol. 2016; 22(3): 327-35. https://www.ncbi.nlm.nih.gov/pubmed/27729634. https://www.ncbi.nlm.nih.gov/pmc/articles/5066376. https://doi.org/10.3350/cmh.2016.0049
  27. Pacana T, Fuchs M. The cardiovascular link to nonalcoholic fatty liver disease. Clin Liver Dis. 2012; 16(3): 599-613. https://www.ncbi.nlm.nih.gov/pubmed/22824483. https://doi.org/10.1016/j.cld.2012.05.008
  28. Povero D, Feldstein AE. Novel Molecular Mechanisms in the Development of Non-Alcoholic Steatohepatitis. Diabetes Metab J. 2016; 40(1): 1-11. https://www.ncbi.nlm.nih.gov/pubmed/26912150. https://www.ncbi.nlm.nih.gov/pmc/articles/4768045. https://doi.org/10.4093/dmj.2016.40.1.1
  29. Milić S, Lulić D, Štimac D. Non-alcoholic fatti liver disease and obesity: Biochemical, metabolic and clinical presentations. World Journal of Gastroenterology. 2014; 20, 28: 9330-7. https://www.ncbi.nlm.nih.gov/pubmed/25071327. https://www.ncbi.nlm.nih.gov/pmc/articles/4110564. https://doi.org/10.3748/wjg.v20.i28.9330
  30. Seki E, Schnabl B. Role of innate immunity and the microbiota in liver fi brosis: rosstalk between the liver and gut. J Physiol. 2012; 590(3): 447-58. https://www.ncbi.nlm.nih.gov/pubmed/22124143. https://www.ncbi.nlm.nih.gov/pmc/articles/3379693. https://doi.org/10.1113/jphysiol.2011.219691
  31. Shanab AA, Scully P, Crosbie O, Buckley M, O'Mahony L, Shanahan F, et all. Small intestinal bacterial overgrowth in nonalcoholic steatohepatitis: Association with toll-like receptor 4 expression and plasma levels of interleukin. Dig Dis Sci. 2011; 56(5): 1524-34. https://www.ncbi.nlm.nih.gov/pubmed/21046243. https://doi.org/10.1007/s10620-010-1447-3
  32. Torres DM, Harrison SA. Nonalcoholic Fatty Liver Disease: Pathophysiology, Dіаgnosіs, Mаnаgement. Ed by Mаrk Feldmаn, Lawrence 5 Friedman, Laurence J Brandt. 10th ed. 2015.
  33. Waly Raphael S, Yangde Z, Yuxiang C. Hepatocellular carcinoma: focus on different aspects of management. ISRN Oncol. 2012; 2012: 1-12. https://doi.org/10.5402/2012/421673
  34. Yang JD, Roberts LR. Epidemiology and management of hepatocellular carcinoma. Infect Dis Clin North Am. 2010; 24(4): 899-919. https://www.ncbi.nlm.nih.gov/pubmed/20937457. https://www.ncbi.nlm.nih.gov/pmc/articles/3949429. https://doi.org/10.1016/j.idc.2010.07.004
  35. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease - Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016; 64(1): 73-84. https://www.ncbi.nlm.nih.gov/pubmed/26707365. https://doi.org/10.1002/hep.28431
  36. Younossi ZM, Otgonsuren M, Henry L, Venkatesan C, Mishra A, Erario M, Hunt S. Association of Nonalcoholic Fatty Liver Disease (NAFLD) with Hepatocellular Carcinoma (HCC) in the United States from 2004-2009. Hepatology. 2015 Dec; 62(6): 1723-30. https://www.ncbi.nlm.nih.gov/pubmed/26274335. doi: 10.1002/hep.28123
  37. Kleiner DE. Histopathology, grading and staging of nonalcoholic fatty liver disease. Minerva Gastroenterologica e Dietologica. 2018 March; 64(1): 28-38. https://www.ncbi.nlm.nih.gov/pubmed/28948754. https://doi.org/10.23736/S1121-421X.17.02445-X
  38. Massoud O, Charlton M. Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis and Hepatocellular Carcinoma. Clin Liver Dis. 2018 Feb; 22(1):201-11. https://www.ncbi.nlm.nih.gov/pubmed/29128057. https://doi.org/10.1016/j.cld.2017.08.014
  39. Santos RD, Valenti L, Romeo S. Does nonalcoholic fatty liver disease cause cardiovascular disease? Current knowledge and gaps. Atherosclerosis. 2019 Jan 30; 282: 110-20. https://www.ncbi.nlm.nih.gov/pubmed/30731283. https://doi.org/10.1016/j.atherosclerosis.2019.01.029
  40. Brar G, Tsukamoto N. Alcoholic and non-alcoholic steatohepatitis: global perspective and emerging science. J Gastroenterol. 2019 Jan 14. https://doi.org/10.1007/s00535-018-01542-w