Terapevticheskii arkhivTerapevticheskii arkhivТерапевтический архив0040-36602309-5342LLC Obyedinennaya Redaktsiya3284410.26442/terarkh201890289-93Editorial articleПередовая статьяReview ArticleMinimal hepatic encephalopathy: current clinical and pathogenetic aspectsМинимальная печеночная энцефалопатия: современные клинические и патогенетические аспектыDamulinI VДамулинИгорь Владимирович

д.м.н., проф. каф. нервных болезней и нейрохирургии Первого МГМУ им. И.М. Сеченова, вед. науч. сотр. МНКЦ им. А.С. Логинова

damulin@mmascience.ruI.M. First Moscow State Medical University, Ministry of Health of RussiaФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава РоссииA.S Loginov Moscow clinical scientific center of the Moscow healthcare DepartmentГБУЗ «Московский клинический научный центр им. А.С. Логинова Департамента здравоохранения Москвы»15022018902VOL 90, NO2 (2018)ТОМ 90, №2 (2018)899311042020Copyright ©; 2018, Consilium MedicumCopyright ©; 2018, ООО "Консилиум Медикум"2018Consilium MedicumООО "Консилиум Медикум"https://creativecommons.org/licenses/by-nc-sa/4.0https://ter-arkhiv.ru/0040-3660/article/view/32844

The review considers modern ideas about the clinic and pathogenesis of minimal hepatic encephalopathy (MHE). It is discussed the present of cognitive impairment in this category of patients. The data of functional MRI are analyzed, and these results allow taking a fresh look at the origin of clinical disorders in this condition. The importance of cerebral connections disruption is emphasized. It is focused on the fact that in the functioning of the central nervous system the spontaneous activity of the brain has a significant importance. Separately is analyzed “the resting state”. It is concluded that MHE, despite its minimal manifestations, is a clinically significant condition requiring attention of a specialists. With that, it is often not diagnosed on time in clinical practice, which could lead to more severe damage of the cerebral functions. As evidenced by the data obtained at the present time, quite extensive changes in the neuronal activity are underlid of the cognitive deficit.

В обзорной статье рассматриваются современные представления о клинической картине и патогенезе минимальной печеночной энцефалопатии (МПЭ). Приводится описание имеющихся у данной категории больных когнитивных нарушений. Анализируются результаты функциональной магнитно-резонансной томографии, результаты которой позволили по-новому взглянуть на происхождение клинических нарушений при этом состоянии. Подчеркивается значение нарушения церебральных связей. Акцентируется внимание на том, что в функционировании ЦНС ведущее значение имеет присущая головному мозгу особенность, связанная с его спонтанной активностью. Отдельно анализируется «состояние покоя». Делается вывод, что МПЭ, несмотря на свои минимальные проявления, является клинически значимым состоянием, требующим внимания специалистов. При этом в практической деятельности оно нередко вовремя не диагностируется, приводя в своем развитии к более грубым нарушениям церебральных функций. В основе когнитивного дефекта, как свидетельствуют полученные в настоящее время данные, лежат довольно обширные изменения нейрональной активности.

minimal hepatic encephalopathyclinical featurespathogenesisresting state activity of the brainfunctional brain imagingминимальная печеночная энцефалопатияклиническая картинапатогенезактивность головного мозга в состоянии покояметоды функциональной нейровизуализацииDhiman R.K. Impact of minimal/covert hepatic encephalopathy on patients with cirrhosis. Clin Liver Dis. 2015;5(3):75-8. doi: 10.1002/ cld.452Lv X-F, Qiu Y-W, Tian J-Z, Xie C-M, Han L-J, Su H-H, Liu Z-Y, Peng J-P, Lin C-L, Wu M-S, Jiang G-H, Zhang X-L. Abnormal regional homogeneity of resting - state brain activity in patients with HBV-related cirrhosis without overt hepatic encephalopathy. Liver International. 2013;33(3):375-83. doi: 10.1111/liv.12096Weissenborn K. Hepatic Encephalopathy. In: Mc Candless D.W (editor). Metabolic Encephalopathy. Ch.10. New York: Springer; 2009. P. 181-99.Lv X-F, Ye M, Han L-J, Zhang X-L, Cai P-Q, Jiang G-H, Qiu Y-W, Qiu S-J, Wu Y-P, Liu K, Liu Z-Y, Wu P-H, Xie C-M. Abnormal baseline brain activity in patients with HBV-related cirrhosis without overt hepatic encephalopathy revealed by resting - state functional MRI. Metab Brain Dis. 2013;28(3):485-92. doi: 10.1007/s11011-013-9420-4Qi R, Zhang L.J, Xu Q, Liang X, Luo S, Zhang Z, Huang W, Zheng L, Lu G.M. Abnormal functional connectivity within the default mode network in patients with HBV-related cirrhosis without hepatic encephalopathy revealed by resting - state functional MRI. Brain Res. 2014;1576:73-80. doi: 10.1016/j.brainres.2014.05.044Zhang L.J, Wu S, Ren J, Lu G.M. Resting - state functional magnetic resonance imaging in hepatic encephalopathy: current status and perspectives. Metab Brain Dis. 2014;29(3):569-82. doi: 10.1007/ s11011-014-9504-9Amodio P, Montagnese S, Gatta A, Morgan M.Y. Characteristics of minimal hepatic encephalopathy. Metab Brain Dis. 2004;19(3/4):253-67. doi: 10.1023/b:mebr.0000043975.01841.deBasu P.P, Shah N.J. Clinical and neurologic manifestation of minimal hepatic encephalopathy and overt hepatic encephalopathy. Clin Liver Dis. 2015;19(3):461-72. doi: 10.1016/j.cld.2015.05.003Chen Q-F, Chen H-J, Liu J, Sun T, Shen Q-T. Machine learning classification of cirrhotic patients with and without minimal hepatic encephalopathy based on regional homogeneity of intrinsic brain activity. PLoS ONE. 2016;11(3):e0151263. doi: 10.1371/journal.pone. 0151263Golaszewski S, Langthaler P.B, Schwenker K, Florea C, Christova M, Brigo F, Trinka E, Nardone R. Abnormal cortical synaptic plasticity in minimal hepatic encephalopathy. Brain Res Bull. 2016;125: 200-4. doi: 10.1016/j.brainresbull.2016.07.011Montgomery J.Y, Bajaj J.S. Diagnosis of Minimal Hepatic Encephalopathy. In: Mullen K.D, Prakash R.K, editors. Hepatic Encephalopathy. Ch.8. New York etc.: Springer, 2012. P.103-112.Montoliu C, Felipo V. Current state of knowledge of hepatic encephalopathy (part II): changes in brain white matter tracts integrity are associated with cognitive deficits in minimal hepatic encephalopathy. Metab Brain Dis. 2016;31(6):1359-60. doi: 10.1007/s11011-016-9909-8Zhong W-J, Zhou Z-M, Zhao J-N, Wu W, Guo D-J. Abnormal spontaneous brain activity in minimal hepatic encephalopathy: resting - state fMRI study. Diagn Intervent Radiol. 2016;22(2):196-200. doi: 10.5152/dir.2015.15208Yadav S.K, Goel A, Saraswat V.A, Thomas M.A, Wang E, Marincola F.M, Haris M, Gupta R.K. Evaluation of cognitivity, proinflammatory cytokines, and brain magnetic resonance imaging in minimal hepatic encephalopathy induced by cirrhosis and extrahepatic portal vein obstruction. J Gastroenterol Hepatol. 2016;31(12):1986-94. doi: 10.1111/ jgh.13427Li S-W, Wang K, Yu Y-Q, Wang H-B, Li Y-H, Xu J-M. Psychometric hepatic encephalopathy score for diagnosis of minimal hepatic encephalopathy in China. World J Gastroenterol. 2013; 19(46):8745-51. doi: 10.3748/wjg.v19.i46.8745Zucco G.M, Amodio P, Gatta A. Olfactory deficits in patients affected by minimal hepatic encephalopathy: a pilot study. Chem Senses. 2006;31(3):273-8. doi: 1093/chemse/bjj029Gupta D.V, Shah K, Solanke D, Ingle M, Sawant P. Predictors of minimal hepatic encephalopathy in patients with cirrhosis and predictors of overt hepatic encephalopathy in patients with minimal hepatic encephalopathy. J Hepatol. 2016;64(2):S256-S257. doi: 10.1016/s0168-8278(16)00282-8Ni L, Qi R, Zhang L.J, Zhong J, Zheng G, Zhang Z, Zhong Y, Xu Q, Liao W, Jiao Q, Wu X, Fan X, Lu G.M. Altered regional homogeneity in the development of minimal hepatic encephalopathy: a resting - state functional MRI study. PLoS ONE. 2012;7(7):e42016. doi: 10.1371/ journal.pone.0042016Butterworth R.F. Pathogenesis of hepatic encephalopathy in cirrhosis: the concept of synergism revisited. Metab Brain Dis. 2015;31(6):1211-1215. doi: 10.1007/s11011-015-9746-1Sangeetha K, Krishnasamy N, Padma K, Rajendran K. Evaluation of oxidative stress in liver cirrhosis patients to early diagnosis of minimal hepatic encephalopathy. Int Neuropsychiat Dis J. 2016;5(3):1-9. doi: 10.9734/indj/2016/19004Zhang L, Qi R, Wu S, Zhong J, Zhong Y, Zhang Z, Zhang Z, Lu G. Brain default - mode network abnormalities in hepatic encephalopathy: A resting - state functional MRI study. Human Brain Mapping. 2011;33(6):1384-92. doi: 10.1002/hbm.21295Zhang L.J, Zhong J, Lu G.M. Multimodality MR imaging findings of low - grade brain edema in hepatic encephalopathy. Am J Neuroradiol. 2012;34(4):707-15. doi: 10.3174/ajnr.a2968Chen H-J, Zhu X-Q, Yang M, Liu B, Zhang Y, Wang Y, Teng G-J. Changes in the regional homogeneity of resting - state brain activity in minimal hepatic encephalopathy. Neuros Lett. 2012; 507(1):5-9. doi: 10.1016/j.neulet.2011.11.033Garcia-Martinez R, Cordoba J. Brain Imaging in Hepatic Encephalopathy. In: Mullen K.D, Prakash R.K, editors. Hepatic Encephalopathy. Ch.10. New York etc.: Springer, 2012. P.123-137.Zhang L.J, Zheng G, Zhang L, Zhong J, Li Q, Zhao T.Z, Lu G.M. Disrupted small world networks in patients without overt hepatic encephalopathy: A resting state fMRI study. Eur J Radiol. 2014;83(10):1890-9. doi: 10.1016/j.ejrad.2014.06.019Guo J.N, Blumenfeld H. Network imaging. In: Faingold C.L, H.Blumenfeld H, editors. Neuronal Networks in Brain Function, CNS Disorders, and Therapeutics. Ch.6. Amsterdam etc.: Elsevier Inc., 2014. P.77-89.Chen H-J, Zhu X-Q, Jiao Y, Li P-C, Wang Y, Teng G-J. Abnormal baseline brain activity in low - grade hepatic encephalopathy: A resting - state fMRI study. J Neurol Sci. 2012;318(1-2):140-5. doi: 10.1016/j.jns.2012.02.019Patel A, Kern M, Babaei A, Samuel E.A, Siwiec R.M, Chen G, Saeian K, Li S-J, Shaker R. Objective diagnosis of minimal hepatic encephalopathy (MHE) by analysis of brain resting state functional connectivity. Gastroenterology. 2013;144(5):S-557-S-558. doi: 10.1016/s0016-5085(13) 62063-6Patel A, Babaei A, Kern M, Samuel E.A, Siwiec R.M, Mankad J, Xie C, Li S-J, Saeian K, Shaker R. Minimal hepatic encephalopathy (MHE) is associated with alterations in brain default - mode network (DMN). Gastroenterology. 2013;144(5):S-558-S-559. doi: 10.1016/s0016-5085(13)62066-1Chen H-J, Jiao Y, Zhu X-Q, Zhang H-Y, Liu J-C, Wen S, Teng G-J. Brain dysfunction primarily related to previous overt hepatic encephalopathy compared with minimal hepatic encephalopathy: resting - state functional MR imaging demonstration. Radiology. 2013;266(1):261-70. doi: 10.1148/radiol.12120026Chen H-J, Zhang L, Jiang L-F, Chen Q-F, Li J, Shi H-B. Identifying minimal hepatic encephalopathy in cirrhotic patients by measuring spontaneous brain activity. Metab Brain Dis. 2016;31(4):761-9. doi: 10.1007/s11011-016-9799-9Nuallain S.O, Doris T. Consciousness is cheap, even if symbols are expensive; metabolism and the brain’s dark energy. Biosemiotics. 2011;5(2):193-210. doi: 10.1007/s12304-011-9136-yErchova I, Mc Gonigle D.J. Rhythms of the brain: An examination of mixed mode oscillation approaches to the analysis of neurophysiological data. Chaos Interdiscipl J Nonlinear Sci. 2008;18(1):015115-1-015115-14. doi: 10.1063/1.2900015Butz M, May E.S, Haussinger D, Schnitzler A. The slowed brain: Cortical oscillatory activity in hepatic encephalopathy. Arch Biochem Biophys. 2013;536(2):197-203. doi: 10.1016/j.abb. 2013.04.004Szpunar K.K, Watson J.M, Mc Dermott K.B. Neural substrates of envisioning the future. Proc Nat Acad Sci. 2007;104(2):642-7. doi: 10.1073/ pnas.0610082104Bar M. Predictions: a universal principle in the operation of the human brain. In: Bar M, editor. Predictions in the Brain. Using Our Past To Generate A Future. Preface. Oxford etc.: Oxford University Press, Inc., 2011. P.v-vii.Szpunar K.K, Tulving E. Varieties of future experience. In: Bar M, editor. Predictions in the Brain. Using Our Past To Generate A Future. Oxford etc.: Oxford University Press, Inc., 2011. P.3-12.Fassbender C, Foxe J.J, Garavan H. Mapping the functional anatomy of task preparation: Priming task - appropriate brain networks. Hum Brain Mapping. 2006;27(10):819-27. doi: 10.1002/hbm.20223Cookson S.L, Hazeltine E, Schumacher E.H. Neural representation of stimulus - response associations during task preparation. Brain Res. 2016;1648:496-505. doi: 10.1016/j.brainres.2016.08.014Sterr A. Preparing not to move: Does no - response priming affect advance movement preparation processes in a response priming task? Biol Psychol. 2006;72(2):154-9. doi: 10.1016/j.biopsycho. 2005.09.002Gregory M.D, Robertson E.M, Manoach D.S, Stickgold R. Thinking about a task is associated with increased connectivity in regions activated by task performance. Brain Connect. 2016;6(2):164-8. doi: 10.1089/ brain.2015.0386