Terapevticheskii arkhivTerapevticheskii arkhivТерапевтический архив0040-36602309-5342LLC Obyedinennaya Redaktsiya3220010.17116/terarkh201789259-65Editorial articleПередовая статьяResearch ArticleDiabetes mellitus and nonalcoholic fatty liver disease: The verges of contingencyСахарный диабет и неалкогольная жировая болезнь печени: грани сопряженностиBakulinI GБакулинИ ГSandlerYu GСандлерЮ ГVinnitskayаE VВинницкаяЕ ВKeiyanV AКейянВ АRodionovaS VРодионоваС ВRotinD LРотинД ЛМосковский клинический научно-практический центр Департамента здравоохранения Москвы15022017892VOL 89, NO2 ()ТОМ 89, №2 (2017)596510042020Copyright ©; 2017, Consilium MedicumCopyright ©; 2017, ООО "Консилиум Медикум"2017Consilium MedicumООО "Консилиум Медикум"https://creativecommons.org/licenses/by-nc-sa/4.0https://ter-arkhiv.ru/0040-3660/article/view/32200

Aim. To estimate the incidence of hepatic steatosis (HS) and liver fibrosis (LF) in patients with diabetes mellitus (DM), by applying the noninvasive techniques of liver fibroelastometry (LFE) and a battery of fibrotests (FTs); to determine their diagnostic value and to identify factors influencing the development of LF. Subjects and methods. A comprehensive examination was made in 82 diabetic patients (mean age, 56.7±12.7 years; p=0.033). The data were statistically evaluated using ROC curve analysis, correlation and single-factor analyses of variance, and multiple logistic regression analysis. Results. FTs and LFE revealed that the DM patients had liver cirrhosis (LC) (METAVIR F4) in 12 (14.6%) and 15 (18.2%) patients, respectively. Those showed clinically significant fibrosis (METAVIR fibrosis stages F2-3) in 19 (23.1%) and 23 (28%) patients, respectively. Varying degrees of HS were present in 79 (96.3%) patients. LFE and FTs demonstrated comparable results in detecting LC (the area under the receiver operating characteristics curve (AUROC), 0.83 and 0.81, respectively). The development of LF is influenced by factors, such as the degree of HS, obesity, the activity of an inflammatory process, and the level of alanine aminotransferase and α2-macroglobulin. Conclusion. Diabetic patients are at high risk for NAFLD to develop LF and LC. LFE and FTs showed a comparably high accuracy in the diagnosis of LC in patients with DM and these may be used for screening. With allowance made for the existing risk factors of LF and LC, it is necessary to identify groups of patients with DM for further examination and follow-up. Patients who are diagnosed with stage F4 should be examined carefully to evaluate concurrent diseases and to make liver biopsy.

Резюме Цель исследования. Оценить частоту развития стеатоза (СП) и фиброза печени (ФП) у больных сахарным диабетом (СД) с применением неинвазивных методов фиброэластометрии печени (ФЭП) и панели фибротестов (ФТ); определить их диагностическую значимость и выявить факторы, влияющие на развитие ФП. Материалы и методы. Комплексно обследовали 82 пациентов с СД (средний возраст 56,7±12,7 года; р=0,033). Проведена статистическая оценка данных с применением ROC-анализа, корреляционного и однофакторного дисперсионного анализа, множественной логистической регрессии. Результаты. Среди пациентов с СД по данным ФТ и ФЭП у 12 (14,6%) и 15 (18,2%) соответственно выявлен цироз печени ЦП (F4 по шкале METAVIR). Клинически значимая стадия фиброза (F2—3) определена у 19 (23,1%) по ФТ и у 23 (28%) по ФЭП. СП различной степени имелся у 79 (96,3%). ФЭП и ФТ демонстрируют сопоставимые результаты при обнаружении цирроза печени (AUROC: 0,83 и 0,81). На развитие ФП влияют такие факторы, как уровень СП, ожирение, активность воспалительного процесса, уровень аланинаминотрансферазы, α2-макроглобулина. Заключение. Пациенты с СД имеют высокий риск развития НАЖБП с формированием ФП и ЦП. ФЭП и ФТ показали сопоставимо высокую достоверность в диагностике ЦП у больных СД и могут применяться для скринингового обследования. С учетом имеющихся факторов риска развития ФП и ЦП необходимо выявлять группы пациентов с СД для дальнейшего обследования и наблюдения. Больные, у которых выявлена стадия F4, должны быть тщательно обследованы для оценки конкурирующих заболеваний и проведения биопсии печени.

liver fibrosistype 2 diabetes mellitusnonalcoholic steatohepatitisfibroelastometry with a controlled ultrasound attenuation parametera battery of fibrotestsфиброз печенисахарный диабет 2-го типанеалкогольный стеатогепатитфиброэластометрия с функцией контролируемого параметра затухания ультразвуканабор фибротестовBlachier M, Leleu H, Peck-Radosavljevic M, Valla DC, Roudot Thoraval F. The burden of liver disease in Europe: a review of available epidemiological data. J Hepatol. 2013;58:593-608.Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA 2015;313:2263-2273.One adult in ten will have diabetes by 2030. International Diabetes Federation. November 14, 2011. Available at http://www.idf.org/media-events/press-releases/2011/diabetes-atlas-5th-editionWilliamson RM, Price JF, Glancy S, Perry E, Nee LD, Hayes PC, et al. Prevalence of and risk factors for hepatic steatosis and nonalcoholic fatty liver disease in people with type 2 diabetes: the Edinburgh Type 2 Diabetes Study. Diabetes Care 2011;34:1139-1144. CrossRef,PubMed,Web of Science® Times Cited: 68Aijaz Ahmed M.D., Ryan B. Perumpail M.D. Stephen A. Harrison M.D. High prevalence of hepatic fibrosis in the setting of coexisting diabetes and hepatic steatosis: A case for selective screening in the general population? Hepatology. 2016;63(1):20-22. doi:10.1002/hep.28277Byrne CD., Targher G. NAFLD: A multisystem disease. Journal of Hepatology. 2015;62:47-64.Younossi ZM, Koening A B, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease — Meta-analytic assessment of prevalence, incidence, and outcomes. 2016;64(1):73-84.Targher G, Bertolini L, Rodella S, et al. Nonalcoholic fatty liver disease is independently associated with an increased incidence of cardiovascular events in Type 2 diabetic patients. Diabetes Care. 2007;30(8):2119-2121.Fracanzani AL, Valenti L, Bugianesi E et al. Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels: a role for insulin resistance and diabetes. Hepatology. 2008;48:792-798.Cusi K. The role of adipose tissue and lipotoxicity in the pathogenesis of Type 2 diabetes. Curr Diab Rep. 2010;10(4):306-315.Richard John and Lingvay Ildiko. Hepatic steatosis and Type 2 diabetes: current and future treatment considerations. Expert Rev Cardiovasc Ther. 2011;9(3):321-328. doi:10.1586/erc.11.15Loomba R, Sanyal AJ. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol. 2013;10:686-690.Michelotti GA, Machado MV, Diehl AM. NAFLD, NASH and liver cancer. Nat Rev Gastroenterol Hepatology 2013;10:656-665.Doycheva I, Cui J, Nguyen P, Costa EA, Hooker J, Hofflich H, Bettencourt R, Brouha S, Sirlin CB, Loomba R. Non-invasive screening of diabetics in primary care for NAFLD and advanced fibrosis by MRI and MRE. Aliment Pharmacol Ther. 2016;43(1):83-95. doi:10.1111/apt.13405Ertle J, Dechene A, Sowa JP, Penndorf V, Herzer K, Kaiser G, et al. Nonalcoholic fatty liver disease progresses to hepatocellular carcinoma in the absence of apparent cirrhosis. Int J Cancer 2011;128:2436-2443.Stickel F, Hellerbrand C. Non-alcoholic fatty liver disease as a risk factor for hepatocellular carcinoma: mechanisms and implications. Gut. 2010;59:1303-1307.Ekstedt M, Hagstrom H., Nasr P., Fredrikson M., Kechagias S., Hultcrantz R. Fibrosis Stage is the srongest predictor for disease-specific mortality in NAFLD After Up to 33 Years of Follow-Up. Hepatology. 2015;61(5):1547-1554. http://onlinelibrary.wiley.com/doi/10.1002/hep.27368/fullEASL-ALEH Clinical Practice Guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis. Journal of Hepatology. 2015;63:237-264.EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. Journal of Hepatology 2016;64:1388-1402.Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313-1321. doi:10.1002/hep.20701Brunt EM, Kleiner DE, Wilson L, Belt P, Neuschhwander-Tetril. Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meaning. Hepatology. 2011;53(3):810-820. http://onlinelibrary.wiley.com/doi/10.1002/hep.24127/full (обращение 08.08.2016)Ratziu V, Charlotte F, Heurtier A, Gombert S, Giral P, Bruckert E, et al. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology 2005;128:1898-1906. CrossRef | PubMed | Web of Science® Times Cited: 624.Merriman RB, Ferrell LD, Patti MG, Weston SR, Pabst MS, Aouizerat BE, et al. Correlation of paired liver biopsies in morbidly obese patients with suspected nonalcoholic fatty liver disease. Hepatilogy. 2006;44:874-880. Wiley Online Library.PubMed.Web of Science® Times Cited: 120Thierry Poynard, Pascal Lebray, Patrick Ingiliz, Anne Varaut, Brigitte Varsat, Yen Ngo, Pascal Norha, Mona Munteanu, Fabienne Drane, Djamila Messous, Françoise Imbert Bismut, Jean Pierre Carrau, Julien Massard1, Vlad Ratziuev. Prevalence of liver fibrosis and risk factors in a general population using non-invasive biomarkers (FibroTest). Giordanella2Poynard et al. BMC Gastroenterology 2010;10:40. http://www.biomedcentral.com/1471-230X/10/40Sumida Y, Nakajima A, Itoh Y. Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Gastroenterol. 2014;20:475-485.Бакулин И.Г., Сандлер Ю.Г., Кейян В.А., Ротин Д.Л. Новый неинвазивный метод оценки стеатоза при хронических заболеваниях печени. Терапевтическийархив. 2016;88(2):49-57.Musso G, Gambino R, Cassader M, Pagano G. Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med. 2011;43:617-649. doi:10.3109/07853890.2010.518623Wong VW, Vergniol J, Wong GL, Foucher J, Chan HL, Le Bail B, Choi PC, Kowo M, Chan AW, Merrouche W, Sung JJ, de Lédinghen V. Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease. Hepatology. 2010;51(2):454-462. doi:10.1002/hep.23312Бакулин И.Г., Сандлер Ю.Г., Винницкая Е.В., Кейян В.А., Драпун С.В. Оценка стеатоза печени с помощью неинвазивного метода: миф или реальность? Доктор.Ру. Гастроэнтерология. 2015;12(113):57-64.Mikolasevic I, Orlic L, Franjic N., Hauser G., Stimac D., Milic S. Transient elastography (FibroScan) with controlled attenuation parameter in the assessment of liver steatosis and fibrosis in patients with nonalcoholic fatty liver disease — Where do we stand? World J Gastroenterol. 2016;22(32):7236-7251. Published online 2016 Aug 28.Article PubReader PDF-1.1MCitation. (обращение 01.09.2016).