UDC

616-092.11:[616.89-008+616.36-002]

DOI

10.17238/issn2542-1298.2019.7.3.327

Authors

Nataliya V. Solov’eva*, Nataliya V. Davidovich*, Veronika A. Solov’eva**, Elena N. Bashilova*
*Northern State Medical University (Arkhangelsk, Russian Federation)
**Northern (Arctic) Federal University named after M.V. Lomonosov (Arkhangelsk, Russian Federation)
Corresponding author: Nataliya Davidovich, address: prosp. Troitskiy 51, Arkhangelsk, 163000, Russian Federation; e-mail: nvdavidovich@gmail.com

Abstract

The leading causes of impaired synthesis of lipids, apoproteins and lipoproteins, which form the basis for fatty transformation, infiltration and steatosis of the liver tissue, are alcohol dependence (AD) and chronic hepatitis C (CHC). In addition, the pathological process during the progression of CHC and AD is characterized by imbalanced production of the key inflammatory immune mediators, i.e. cytokines, inducing a systemic response, including damage to the vascular wall, which, together with atherogenic dyslipidaemia, plays a significant role in the development of atherosclerosis and cardiovascular diseases associated with it. We aimed to conduct a comparative analysis of impaired lipid metabolism and cytokine production in AD and CHC. The research involved 209 residents of the city of Arkhangelsk, including 44 patients with AD, 86 with CHC and 79 practically healthy individuals. We applied biochemical (determination of the lipid spectrum and the content of alipoproteins (apo) A and B), immunological (determination of the content of cytokines TNF-α, IFN-γ, IL-1β, IL-6, IL-8, IL-4 and IL-10) and statistical research methods. As a result, the following common features of metabolic disorders in the groups of patients with AD and CHC were revealed: dyslipidaemia associated with inhibition of the synthesis of apo-A, which are part of high-density lipoproteins, and high content of apo-B, which are part of atherogenic low-density lipoproteins. We found that increased synthesis of pro-inflammatory cytokines IL-1β and IFN-γ plays a central role in the manifestation of the inflammatory process and in the activation of cytotoxic effector mechanisms leading to liver damage in both patients with AD and patients with CHC. Thus, AD and CHC are associated with lipid metabolism disorders and with immunoinflammatory responses contributing to the development of hepatic steatosis and fibrosis.

Keywords

alcohol dependence, chronic hepatitis C, lipid metabolism, apolipoproteins, cytokine profile

References

1. Chibyeva L.G., Gatilova M.I. Sravnitel’naya kharakteristika klinicheskikh proyavleniy khronicheskogo gepatita alkogol’noy, alkogol’no-virusnoy i virusnoy etiologii v usloviyakh Severa [Comparative Characteristics of Clinical Manifestations of Chronic Hepatitis of Alcoholic, Alcoholic-Viral and Viral Etyology in the North]. Vestnik Severo- Vostochnogo federal’nogo universiteta im. M.K. Ammosova. Ser. Meditsinskie nauki, 2016, no. 3, pp. 108–110.
2. Vyaz’min A.M., Mordovskiy E.A., Solov’ev A.G. Cmertnost’ ot sostoyaniy, svyazannykh s upotrebleniem alkogolya [Mortality from Conditions Associated with Alcohol Consumption]. Problemy sotsial’noy gigieny, zdravookhraneniya i istorii meditsiny, 2013, no. 2, pp. 13–16.
3. Mordovskiy E.A., Solov’ev A.G., Vyaz’min A.M., Kuzin S.G., Kolyadko E.A. Potreblenie alkogolya nakanune smerti i smertnost’ ot travm, otravleniy i drugikh posledstviy deystviya vneshnikh prichin [Alcohol Consumption the Day Before Death and Mortality from Traumas, Intoxications and Other Effects of External Causes]. Ekologiya cheloveka, 2014, no. 9, pp. 24–29.
4. Baramzina S.V. Khronicheskaya HCV-infektsiya: epidemicheskaya i epidemiologicheskaya kharakteristika zabolevaniya v raznykh vozrastnykh gruppakh za 14-letniy period nablyudeniya [Chronic HCV-Infection: Epidemical and Epidemiological Characteristic of the Disease of Different Age Groups for 14 Years Examination Period]. Meditsinskiy al’manakh, 2014, no. 1, pp. 34–37.
5. Drapkina O.M., Bueverova E.L., Ivashkin V.T. Aterogennaya dislipidemiya i pechen’ [Atherogenic Dyslipidemia and Liver]. Ateroskleroz i dislipidemii, 2010, no. 1, pp. 25–31.
6. Yoon E.J., Hu K-Q. Hepatitis C Virus (HCV) Infection and Hepatic Steatosis. Int. J. Med. Sci., 2006, vol. 3, no. 2, pp. 53–56.
7. Vovk E.I. Alkogol’naya bolezn’ pecheni (ABP) kak sistemnoe zabolevanie: klinicheskie rakursy i taktika lecheniya [Alcoholic Liver Disease (ALD) as a Systemic Disease: Clinical Perspectives and Treatment Tactics]. Russkiy meditsinskiy zhurnal, 2013, vol. 21, no. 20, pp. 993–1002.
8. Aronov D.M., Lupanov V.P. Nekotorye aspekty patogeneza ateroskleroza [Atherosclerosis and Coronary Heart Disease: Some Aspects of Pathogenesis]. Ateroskleroz i dislipidemii, 2011, no. 1, pp. 48–56.
9. Baydina T.V., Mishlanov V.Yu., Danilova M.A. Tsitokinovyy profil’ bol’nykh s ateroskleroticheskim porazheniem sonnykh arteriy [Cytokine Profile of Patients with Arterial Sclerotic Disease of arteria carotis]. Meditsinskiy al’manakh, 2011, no. 1, pp. 56–58.
10. Ross R., Glomset J., Harker L. Response to Injury and Atherogenesis. Am. J. Pathol., 1977, vol. 86, no. 3, pp. 675–684.
11. Al’tshuler V.B. Alkogolizm [Alcoholism]. Moscow, 2010. 264 p.
12. Perlemuter G., Sabile S., Letteron P., Vona G., Topilco A., Chrétien Y., Koike K., Pessayre D., Chapman J., Barba G., Bréchot C. Hepatitis C Virus Core Protein Inhibits Microsomal Triglyceride Transfer Activity and Very Low Density Lipoprotein Secretion: A Model of Viral-Related Steatosis. FASEB J., 2002, vol. 16, no. 2, pp. 185–194.
13. Tkachenko L.I., Maleev V.V., Sarieva D.M. Narushenie lipidnogo obmena u bol’nykh khronicheskim virusnym gepatitom C [Lipid Metabolism Disorders in Patients with Chronic Hepatitis C]. Arkhiv” vnutrenney meditsiny, 2015, no. 6, pp. 50–56.
14. Tarasova O.I., Ogurtsov P.P., Mazurchik N.V., Moiseev V.S. Sovremennye laboratornye markery upotrebleniya alkogolya [Modern Laboratory Markers of Alcohol Consumption]. Klinicheskaya farmakologiya i terapiya, 2007, vol. 16, no. 1, pp. 10–15.
15. Panina V.L., Zykov V.A., Tuzikov M.F. Izmeneniya lipoproteinovogo spektra syvorotki krovi u bol’nykh khronicheskim alkogolizmom [Changes of Blood Serum Lipoprotein Spectrum in Patients with Chronic Alcoholism]. Byulleten’ Sibirskogo otdeleniya RAMN, 2010, vol. 30, no. 2, pp. 70–74.
16. Qu B., Qu T., Liu Y., Jia Y., Han X., Su J., Wang H., Liu L., Wang Z., Wang Y., Pan J., Ren G. Risk Factors Associated with Increased Carotid Intima-Media Thickness in a Male Population with Chronic Alcohol Consumption: A Prospective Observational Study. Medicine (Baltimore), 2016, vol. 95, no. 15. Art. no. e3322.
17. Shekhtman S.V., Fedorov I.V., Dorofeevskaya A.S. Izmeneniya kliniko-laboratornykh pokazateley u patsientov pri ostroy alkogol’noy intoksikatsii [Changes in Clinical Laboratory Parameters in Patients with Acute Alcohol Intoxication]. Meditsina v Kuzbasse, 2014, no. 3 (spec. iss.), pp. 137–138.
18. Lacerda G.S., Medeiros T., Rosário N.F.D., Peralta R.H.S., Cabral-Castro M.J., Esberard E.B.C., Andrade T.G., Xavier A.R., Silva A.A. Exploring Lipid and Apolipoprotein Levels in Chronic Hepatitis C Patients According to Their Response to Antiviral Treatment. Clin. Biochem., 2018, vol. 60, pp. 17–23.
19. Lin M.S., Guo S.E., Lin H.S., Hsu J.T., Lin Y.S., Lin T.H., Huang T.J., Chen M.Y., Chung C.M. Impact of Apolipoprotein B on Hepatosteatosis in a Population Infected with Hepatitis C Virus: A Cross-Sectional Observational Study. Obes. Facts, 2016, vol. 9, no. 2, pp. 101–111.
20. Koryakin A.M., Epifantseva N.N., Eshcheva L.A., Dement’eva L.A., Yakimovskikh A.V. Povrezhdenie, vospalenie sosudistogo endoteliya, giperkoagulyatsiya kak faktory riska serdechno-sosudistykh zabolevaniy u bol’nykh khronicheskim alkogolizmom [Damage, Inflammation of the Vascular Endothelium, Hypercoagulable as a Risk Factor for Heart Diseases in Patients with Chronic Alcoholism]. Sibirskiy meditsinskiy zhurnal, 2014, vol. 29, no. 4, pp. 52–55.
21. Duncan B.B., Schmidt M.I., Pankow J.S., Ballantyne C.M., Couper D., Vigo A., Hoogeveen R., Folsom A.R., Heiss G. Low-Grade Systemic Inflammation and the Development of Type 2 Diabetes: The Atherosclerosis Risk in Communities Study. Diabetes, 2003, vol. 52, no. 7, pp. 1799–1805.
22. Igonina N.A., Zhuravleva E.A., Kondrasheva E.A., Torshina I.G., Chashchikhina E.V., Makarova T.A., Kopaeva L.B., Sysoeva S.N. Analiz dannykh massovogo issledovaniya urovnya kholesterina u naseleniya (k voprosu o referensnykh znacheniyakh kholesterina) [The Analysis of Data of Large Study of Cholesterol Level in Population (on the Issue of Reference Values of Cholesterol)]. Klinicheskaya laboratornaya diagnostika, 2013, no. 1, pp. 11–17.
23. Tenyukova K.Yu., Markov D.S. Skriningovye issledovaniya lipidnogo obmena dlya svoevremennoy diagnostiki i profilaktiki ateroskleroza [Screening Research into Lipid Metabolism for Timely Diagnosis and Prevention of Atherosclerosis]. Vestnik Chuvashskogo universiteta, 2011, no. 3, pp. 463–466.
24. Shakhanova A.T., Kozhakhmetova D.K., Nurtazina A.U. Rol’ dislipidemii, izbytochnoy massy tela i kharaktera pitaniya v formirovanii serdechno-sosudistogo riska pri arterial’noy gipertenzii. Obzor literatury [The Role of Dyslipidemia, Overweight and Diet in the Formation of Cardiovascular Risk in Hypertension. Review]. Nauka i zdravookhranenie, 2017, no. 2, pp. 144–158.
25. Solov’eva V.A., Bichkaeva F.A., Solov’eva N.V., Udovenkova L.P. Narusheniya lipidnogo obmena pri khronicheskoy alkogol’noy intoksikatsii [Lipid Metabolism Disorders in Chronic Alcohol Intoxication]. Vestnik Severnogo (Arkticheskogo) federal’nogo universiteta. Ser.: Mediko-biologicheskie nauki, 2016, no. 4, pp. 67–72.
26. MeQueen M.J., Hawken S., Wang X., Ounpuu S., Sniderman A., Probstfield J., Steyn K., Sanderson J.E., Hasani M., Volkova E., Kazmi K., Yusuf S. Lipids, Lipoproteins, and Apolipoproteins as Risk Markers of Myocardial Infarction in 52 Countries (the INTERHEART Study): A Case-Control Study. Lancet, 2008, vol. 372, no. 9634, pp. 224–233.
27. Johansson L., Schmidt C. Increased apoB/apoA-I Ratio Is Predictive of Peripheral Arterial Disease in Initially Healthy 58-Year-Old Men During 8.9 Years of Follow-Up. Angiology, 2009, vol. 60, no. 5, pp. 539–545.
28. Belyaeva I.G., Gritsaenko G.A., Teregulova A.M., Mingazetdinova L.N. Subklinicheskoe vospalenie i tsitokinovyy status u bol’nykh arterial’noy of gipertoniey s metabolicheskimi faktorami riska [Subclinical Inflammation and Cytokine Status in Hypertensive Patients with Metabolic Risk Factors]. Sovremennye naukoemkie tekhnologii, 2012, no. 6, pp. 10–13.
29. Solov’eva N.V., Davidovich N.V., Bazhukova T.A., Agafonov V.M. Rol’ narusheniy mikroflory tolstoy kishki v mekhanizmakh povrezhdeniya pecheni pri khronicheskikh gepatitakh B i C [The Role of Gut Microflora in the Mechanisms of Liver Damage in Chronic Hepatitis B and C]. Patologicheskaya fiziologiya i eksperimental’naya terapiya, 2017, no. 61, pp. 92–98.
30. Davidovich N.V., Solov’eva N.V., Bashilova E.N. Nekotorye pokazateli tsitokinovogo profilya bol’nykh khronicheskim virusnym gepatitom C na fone interferonoterapii [Some Indicators of Cytokine Profile in Patients with Chronic Viral Hepatitis C Undergoing Interferon Treatment]. Vrach-aspirant, 2016, vol. 74, no. 1.1, pp. 116–122.