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11
Сибирский медицинский журнал (Иркутск), 2019, № 4
оригинальные исследования
© УРАНБАЙГАЛЬ ЭНХБАЯР, ДАВААЛХАМ ДАМБАДАРЖАА, ОТГОНБАЯР РАДНАА - 2019
УДК: 616.36-002.17:[616.36-002.2-022.6+616.36-003.826]-091.8 001: 10.34673/вши.2019.96.18.007
сывороточный уровень M2BPGi в диагностике фиброза печени у пациентов с избыточной массой тела и ожирением в монголии
Уранбайгаль Энхбаяр, Даваалхам Дамбадаржаа, Отгонбаяр Раднаа (Монгольский национальный университет медицинских наук, Улан-Батор, Монголия)
Резюме.
Цель работы: оценить диагностические возможности сывороточного биомаркера M2BPGiB выявлении фиброза печени среди людей с избыточной массой тела и ожирением в возрасте от 40 до 65 лет в Монголии.
Материалы и методы. Обследовали 3315 человек в возрасте 40-65 лет, проживающих в городских и сельских районах. От участников исследования были получены заполненные анкеты, были проведены антропометрические измерения, УЗИ и лабораторные исследования. Уровень M2BPGi в сыворотке измеряли непосредственно с помощью хемилюминесцентного иммуноферментного метода с использованием автоматического иммуноанализатора. Статистический анализ был выполнен на SPSS вер. 20.0 (SPSSInc., Чикаго, Иллинойс, США). Мы использовали хи-квадрат Пирсона для оценки разницы между параметрами в процентах, а критерий Т - для оценки медианной разницы. Значение p<0,05 считается статистически значимым.
Результаты. Из 3315 участников исследования 1955 человек были набраны в Улан-Баторе (59,0%), 1360 человек были из сельской местности. Среди обследованных 1141 (34,4%) были мужчины и 2174 (65,6%) - женщины. 1326 (40%) опрошенных имели избыточную массу, а 1038 (31,3%) страдали ожирением. Фиброз печени был обнаружен у 51,2% пациентов с ожирением и избыточной массой. Повышение уровня биомаркера M2BPGI в сыворотке значительно отличалось от массы тела, возрастной группы и пола (р <0,0001).
Заключение. Из общего числа участников 40% имели избыточный вес и 31,3% страдали ожирением. Фиброз печени был обнаружен у 51,2% пациентов с ожирением и избыточной массой.
Ключевые слова: M2BPGI; HCC; неалкогольная жировая болезнь печени; Y93H; Монголия.
THE sERuM M2BpGi LEvEL cAN BE pRAcTicAL ТЕБТ TO DiAGNOsE LivER FiBROsis AMONGOvERwEiGHT And OBEsE pATIENTs In Mongolia
Uranbaigali Enkhbayar, Davaalkham Dambadarjaa, Otgonbayar Radnaa (Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia)
Summary.
Aim: To diagnose liver fibrosis among overweight and obese population of 40-65 years in Mongolia by serum M2BPGi glyco-biomarker level.
Methods. We enrolled 3315 people aged 40-65 years old who live in urban and rural areas. Questionnaires were obtained from participants, and anthropometric measurements, ultrasound, and laboratory tests were done. Serum M2BPGi level was directly measured with the chemilumines centenzyme immune method using an automatic immunoanalyzer. Statistical analysis was performed on SPSS ver. 20.0; SPSS Inc., Chicago, IL software. We used Pearson chi squaretest to estimate difference between parameters with percentage, and T test was used to estimate median difference. Ap value less than 0.05considered statistically significant.
Results. 3315 people participated in this study. 1955 people were recruited from Ulaanbaatar (59.0%) 1360 people were from rural areas, and 1141 (34.4%) were male and 2174 were female (65.6%). 1326 (40%) of the surveyed were overweight and 1038 (31.3%) were obese. Elevation of serum M2BPGI glyco-biomarker was significantly different from body weight, age group and sex (p<0.0001).
Conclusion. From total participants, 40% were overweight and 31.3% were obese. The liver fibrosis was found in 51.2% of obese and overweight patient.
Key words: M2BPGI;HCC; NAFLD; Y93H; Mongolia.
Introduction
Fatty liver is classified as alcoholic and non-alcoholic causes, and non-alcoholic fatty liver is caused by obesity. Recent study proved that fatty liver was found in 90% of the obese patients [8,17,18]. By collaboration study of the WHO, Millennium Challenge Account and Public Health Institute, in 2009, 42.7 percent of the population aged 1564 years had overweight andobesity. Nonalcoholic fatty liver disease (NAFLD) is characterized by increased hepatic triglyceride accumulation in the absence of excessive alcohol consumption. This condition is a precursor of other liver pathological conditions, including steatohepatitis, liver fibrosis, liver cirrhosis, and liver failure or hepatocellular carcinoma [4]. Mongolia has the highest hepatocellular carcinoma incidence in the world (78.1/100,000, 3.5* higher than China) [3,5]. Most common etiology for HCC was HCV infection 45.6%, followed by HBV infection 34.4%
in Mongolia [6]. Prevalence of HCV infection was 15.6% among apparently healthy populations in Mongolia [4] and ledipasvir/sofosbuvir therapy achieves a high SVR rate in Mongolia chronic hepatitis C genotype 1b patients without baseline Y93H RAS [13].
Furthermore, NAFLD has become more prevalent globally, affecting approximately 25% of the general population [29]. It has an estimated worldwide prevalence ranging from 20% to 46%, varying with study population and diagnostic criteria used [7]. In the United States, NAFLD is estimated to affect approximately 30% (100 million) of the population [14,20]. The prevalence is even higher amongst obese (70%) and diabetic (90%) individuals [11]. In addition, NAFLD is an independent cardiovascular disease risk factor with a 70% overall mortality increase, driven by a about 300% increase in cardiovascular disease mortality [2]. This has generated a need to investigate tools for improving the management of lifestyle or other factors.
To diagnosing liver fibrosis is important for predict the survival rate of chronic liver disease and for the appropriate treatment. Liver biopsy is a golden standard for diagnosing liver fibrosis, but there are several weaknesses. Liver biopsy has several complications such as pain and bleeding which accounts for 1-14%. Therefore, it is necessary to introduce non-invasive methods for assessing liver fibrosis in clinical use. Non-invasive radiologic method and laboratory analysis are used for the detection of liver fibrosis. Moreover, there are several disadvantages for using the diagnostic elastographic to diagnose liver fibrosis. It is challenging to evaluate the function and structure of liver due to deep location where anatomically located under the ribs, and he fluid of abdomen and pregnant women, overweight and obese people have more thick adipose tissue. Japanese scientists have identified the structure of the glycoprotein in the hepatocyte cell wall, which is characterized by a hepatic glyco-biomarker M2BPGI known as the liver fibrous marker. This biomarker may be able to identify fibrosis changes in fatty liver disease and viral hepatitis. Clinical trials compared the M2BPGi test with the liver biopsy tests and it demonstrated same results. In other words, M2BPGi showed negative results in patients with non-inflammatory chronic liver disease,M2BPGI COI = 1.0-3.0 + result in patients with fibrosis group and showed M2BPGI COI> 3.0 + + result in patients with liver cirrhosis [1, 10, 22, 28]. The diagnostic ability of M2BPGi on liver fibrosis is comparableto that of Virtual Touch Tissue Quantification (Siemens, Mountain View, CA, USA) [23], one of the latest shear wave elastography, and superior to other surrogate markers(liver-to-major psoas muscle intensity ratio, serum markers including hyaluronic acid, type 4 collagen and aspartate transaminase to platelet ratio index) [22]. The glyco-biomarker is the most suitable method for use in non-hospital-based research and it is effective, regardless of the cause of liver disease.
Aim: To diagnose the liver fibrotic changes among Mongolian population who aged 40-65 with excess weight using M2BPGi serum glyco-biomarker.
Objectives:
1. Identify changes in body weight among the population aged 40-65 years in Mongolia.
2. Assess the fibrotic change of a liver in the population with the body weight change using serum M2BPGi glyco-biomarker.
Materials and Methods
Sampling
The study was conducted from October 2016 to February 2019, based on the clinical laboratory of the University Hospital at the Mongolian National University of Medical Sciences. In order to reflect the administrative and geographical features of Mongolia, we involved 3315 participants age of 40-65 from Ulaanbaatar city, GobiAltai, Uvs provinces from Western region, Arkhangai and Khuvsgul provinces from Khangai region, Dornogobi, Umnugobi and Tuv provinces from Central region, and Sukhbaatar province from Eastern region. This study was conducted using "Analytical cross sectional survey" type.
Parameters: n- sample size, p - expected prevalence, z -statistic for a level of confidence, e - the acceptable sampling error, DE - desired margin of error.
Inclusion criteria:
- 40-64 years old while participating in the study,
- Citizen of Mongolia,
- Participant and the caregiver must have given approval to participate in the study.
Exclusion criteria:
- Liver cancer is diagnosed.
Questionnaire, body measurement, abdominal ultrasound and lab tests were done on all participants.
Obesity is calculated using BMI and classified as below.
BMI=Body weight (kg)/ Height (m2)
<18,5 kg/m2 - underweight,
18,5-24,9 kg/m2 - normal weight,
25,0 - 29,9 kg/m2 - overweight,
>30,0 kg/m2 - obesity.
Laboratory testing
Serum M2BPGi analysis was performed using Japanese fully automatic HISCL-5000 immunology analyzer by chemiluminescent enzyme immunoassay method.
1. If 1.0 < COI < 3.0s then (+)
2. IfCOI> 3.0 then (++)
3. If COI< 1.0 then (negative)
Statistical analysis was done on SPSS ver.20.0 SPSS ver. 20.0; SPSS Inc., Chicago, IL software and the result was detailed as descriptive, narrow statistical analysis. After determining whether the variable percentage is normal, the margin between parameters were calculated by using Pearson's Chi square test of variables expressed in percentage, the margin of averages was calculated by using T-test. If the p value is less than 0.05, the margin is assumed to be statistically true.
Ethical statement
The research study was approved by the Research Ethics Committee of the Mongolian National University of Medical Sciences (№8/3/2016-08). All participants gave written informed consent.
Results and Discussion
A total of 3451 people aged 40-65 years were elected by random sampling and statistical data were provided for 3315 people covered by all the research stages. Of the respondents, 1955 (59.0%) were from Ulaanbaatar and 1360 (41.0%) were from rural areas. Of these, 1141 (34.4%) were male and 2174 (65.6%) were female and 990 (29.9%) were 40-44 years old, 786 (23.7%) were 45-49 years old, 702 (21.2%) were 50-54 years old, 547 (16.5%) were 55-59 years old and 290 (8.7%) were 60-64 years old.
Table 1
Baseline characteristics of the participants (Region, age, sex)
Baseline characteristics
Region number %
Rural 1360 41.0
Urban 1955 59.0
Sex
Male 1141 34.4
Female 2174 65.6
Age
40-44 990 29.9
45-49 786 23.7
50-54 702 21.2
55-59 547 16.5
60-64 290 8.7
Body weight changes and obesity was measured by BMI. Of total participants, 33 (1%) of had underweight, 918 (27.7%) had a normal weight, 1326 (40%) were overweight and 1038 (31.3%) had obesity. The proportion of people with underweight was 1.4% in age 40-44, 0.5% -0.7% in age group 45-59, and 2.4% in age 60-64 years. Percentage of people with normal weight in age group was close, but the proportion of overweight among 40-44 and 50-54 years old was higher, and the proportion of people with obesity was significantly increased from 28.3% to 40.7% in older age groups (p < 0.0001).In urban and rural areas, the body weight was similar, but 30.6% of men and 26.2% of women have normal body weight. Overweight and obesity were significantly higher in women than men (p = 0.049).
Serum M2BPGI glyco-biomarker was negative in 60.6% of people with normal weigh, 35.1% (+), 4.3% (++), 51.6% of people with overweight, 45.4% (+) (++) in 3.0% (++), 45.3% in obese people, 50.6% in (+), 4.0% (++), indicating higher
Body Mass Index: Age, sex, region difference
Underweight Normal weight Overweight Obese P value
n |% n |% n |% n |%
Age 0.0001
40-44 14 1.4% 279 28.2% 417 42.1% 280 28.3%
45-49 4 0.5% 253 32.2% 304 38.7% 225 28.6%
50-54 4 0.6% 184 26.2% 290 41.3% 224 31.9%
55-59 4 0.7% 135 24.7% 217 39.7% 191 34.9%
60-64 7 2.4% 67 23.1% 98 33.8% 118 40.7%
Sex 0.049
Male 12 1.1% 349 30.6% 445 39.0% 335 29.4%
Female 21 1.0% 569 26.2% 881 40.5% 703 32.3%
Region 0.472
Rural 11 0.8% 390 28.7% 528 38.8% 431 31.7%
Urban 22 1.1% 528 27.0% 798 40.8% 607 31.0%
the body mass index higher the M2BPGI glyco-biomarker (p <0.0001). There was a statistically significant difference between BMI, age group and sex (p <0.0001).
M2BPGI change: Age, sex, region
M2BPGi COI< 1.0 1.0<COI< 3.0 COI >3.0 P value
(negative) (+) (++)
n % n % n %
BMI 0.0001
Underweight 24 77.4% 7 22.6% 0 0.0%
Normal 524 60.6% 303 35.1% 37 4.3%
Overweight 643 51.6% 566 45.4% 38 3.0%
Obese 438 45.3% 489 50.6% 39 4.0%
Age 0.0001
40-44 567 60.0% 360 38.1% 18 1.9%
45-49 444 59.0% 287 38.2% 21 2.8%
50-54 321 47.6% 318 47.2% 35 5.2%
55-59 228 44.1% 267 51.6% 22 4.3%
60-64 105 37.6% 154 55.2% 20 7.2%
Sex 0.002
Male 613 56.9% 425 39.5% 39 3.6%
Female 1052 50.3% 961 46.0% 77 3.7%
Region 0.001
Rural 767 56.2% 559 41.0% 39 2.9%
urban 898 49.8% 827 45.9% 77 4.3%
Increased M2BPGI protein significantly increases abnormalities in the abdominal ultrasound (p <0.0001).
Abdominal ultrasound changes
COI< 1.0 (negative) 1.0<COI< 3.0 (+) COI>3.0 (++) P value
n |% n 1 % n |%
Echogenicity 0.0001
Normal 794 48.7% 545 39.9% 48 41.7%
Slightly increased 362 22.2% 323 23.6% 30 26.1%
Increased 473 29.0% 497 36.4% 37 32.2%
Decreased 3 0.2% 1 0.1% 0 0.0%
Structure 0.0001
Regular 1545 96.1% 1252 92.7% 87 77.0%
Irregular 63 3.9% 99 7.3% 26 23.0%
Capsular contour 0.0001
Smooth 1521 98.7% 1270 97.5% 90 84.9%
Coarse 20 1.3% 32 2.5% 16 15.1%
Hepatic vein 0.104
Normal 1559 98.6% 1306 98.0% 107 99.1%
Dilated 6 0.4% 2 0.2% 1 0.9%
Narrowed 16 1.0% 24 1.8% 0 0.0%
Hepatocystic duct 0.294
Normal 1564 99.2% 1311 98.9% 105 99.1%
Dilated 2 0.1% 3 0.2% 1 0.9%
Narrowed 10 0.6% 12 0.9% 0 0.0%
Masses 0.108
Not occured 1403 87.3% 1156 86.2% 91 80.5%
Occured 204 12.7% 185 13.8% 22 19.5%
The survey covered 3315 people aged 40-65 years in Mongolia. NAFLD comprises a spectrum of disease that can be simplified into two categories: (1) Simple Steatosis (SS),
Table 2 70-75% of cases, defined by excess liver fat without inflammation or cellular injury; and (2) nonalcoholic steatohepatitis (NASH), 25%-30% of cases, defined by the presence of excess liver fat with inflammation and cellular injury [7,26].
It is important to appreciate that SS and NASH are not entirely distinct, with many patients falling along a spectrum of fatty accumulation, inflammation, and hepatocyte injury. Nonetheless, this simplification facilitates prognostication and assessment of clinical significance. In most cases, SS is non-progressive, and does not result in liver fibrosis or progressive liver disease. However, recent longitudinal paired biopsy studies have shown that some patients with SS can progress to develop inflammation and fibrosis [19], and up to 20-30% can progress to NASH [27]. Patients with NASH have a 20%-50% risk of developing progressive Table 3 inflammation or liver fibrosis [21,26] and have a 2-20% 5-year cumulative incidence of hepatocellular carcinoma [25]. According to our study, 1326 (40%) of people surveyed were overweight and 1038 (31.3%) were obese. Clinical trials have shown that M2BPGi glyco-biomarker result was close to liver biopsy test, besides M2BPGi in a group of no chronic liver inflammation was negative, in a group of chronic liver inflammation with fibrotic change was (+), and in a group of cirrhotic patients was (++). Furthermore, the results in our study 51.6% participants from overweight group showed negative M2BPGi, 45.4% is (+), 3.0% (++); in obese group negative M2BPGi was in 45.3%, (+) in 50.6, and (++) in 4.0% of participants, which is close to the results of other research works, that claims liver inflammation and liver fibrosis changes occur in 20-50 percent of obese population. Abe M, Miyake T, Kuno A, et al study showed that M2BPGi glyco-biomarker is effective glyco-biomarker to assess fibrotic changes in alcoholic and non-alcoholic fatty liver disease patients [1]. M2BPGi is a significantly effective glyco-biomarker for the diagnosis of fibrosis levels in patients with hepatitis C [15] and is applicable in the evaluation of outcome of the combination therapy with pegylated interferon and ribavirin. The result of combined treatment of PEG-Interferon and Ribavirin for chronic HCV patients in Mongolia was 78% [24]. Table 4 A high M2BPGi level predicts the onset of hepatic carcinoma[16]. The diagnostic ability of M2BPGi on liver fibrosis is comparable to that of Virtual Touch Tissue Quantification (Siemens, Mountain View, CA, USA) [23], one of the latest shear wave elastography, and superior to other surrogate markers (liver-to-major psoas muscle intensity ratio, serum markers including hyaluronic acid, type 4 collagen and aspartate transaminase to platelet ratio index) [22]. In the analysis of 707 patients infected with hepatitis C virus, the onset risk of hepatic carcinoma increased proportionally with the increase of M2BPGi levels [28]. M2BPGi is an effective glyco-biomarker for the evaluation of fibrosis in patients with nonalcoholic fatty liver disease [29]. The onset risk of hepatic carcinoma is significantly high in patients with M2BPGi levels of 4.2 and higher. Hepatocellular carcinoma is the most common cancer in Mongolia, occurring at a rate of 54.1 cases in 100,000 people [5]. M2BPGi and AFP are independent risk factors. M2BPGi is effective for the evaluation of fibrosis in patients infected with hepatitis B virus, but with a different cut-off value [10]. As stated above, we proved that M2BPGi is an effective glyco-biomarker for the objective evaluation of fibrosis, regardless of the causative liver disease. There fore, based on the data of the survey, there is an urgent need for monitoring of this disease in Mongolia, besides it is necessary to implement early detection, risk identification, epidemic and prevention strategies according to the WHO's Hepatic Disease Prevention Policy and Guidelines.
Conclusion
From total participants, 40% were overweight and 31.3% were obese. The proportion of people with obesity increases with age. The liver fibrosis was detected 49.7% in women and 43.1% in men and it was increasing 40% to 62.4% in age group. 48.4% of people with overweight and 54.6% of obesity patients have found liver fibrosis changes.
Конфликт интересов. Авторы заявляют об отсутствии конфликта интересов. / Conflict of Interest. The authors declare that they have no competing interests.
Прозрачность исследования. Исследование не имело спонсорской поддержки. Исследователи несут полную ответственность за предоставление окончательной версии рукописи в печать. / Transparency of research. The study did not have sponsorship. Researchers are solely responsible for providing the final manuscript in print.
Декларация о финансовых и иных взаимодействиях. Все авторы принимали участие в разработке концепции и дизайна исследования и в написании рукописи. Окончательная версия рукописи была одобрена всеми авторами. Авторы не получали гонорар за исследова-
литература
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ние. / Declaration of financial and other interactions. All
authors participated in the development of the concept and design of the study and in the writing of the manuscript. The final version of the manuscript was approved by all authors. The authors did not receive a research fee.
Благодарности. Мы хотели бы поблагодарить сотрудников монгольского представительства корпорации Sysmex (Япония) и корпорации Sysmex Японии, Медицинский факультет, Монгольский национальный университет медицинских наук, Улан-Батор, Монголия), Университетской больницы общего профиля MNUMS, Научно-технологического фонда MNUMS и Proliance LLC, за помощь в завершении этого исследовательского проекта. / Acknowledgements. We would like to thank the staff at the Mongolian Representative Office of the Sysmex Corporation (Japan) and Sysmex Corporation of Japan, School of Medicine, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia), University General Hospital of MNUMS, Science Technology Foundation of MNUMS and Proliance LLC, for their help in completing this research project.
Материал поступил в редакцию: 31.08.2019 г.
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Информация об авторах:
Отгонбаяр Раднаа - профессор, доктор медицины, доктор философии, профессор кафедры педиатрии, декан Школы медицины Монгольского Национального университета медицинских наук, e-mail: otgonbayar_r@mnums.edu.mn
Information About the Authors:
Otgonbayar Radnaa - MD, PhD, MPH, Professor of Department of Pediatrics,Dean School of Medicine, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia, e-mail:otgonbayar_r@mnums.edu.mn, Mongolian National University of Medical Sciences, Zorig street, POB-48/111, Ulaanbaatar-14210, Mongolia
© ЛАТИФОВА Н.Ф. - 2019
УДК: 616.61+617.586]-02:616.379-008.64)-085 001: 10.34673/вти.2019.39.61.008
роль некоторых цитокинов при диабетической нефропатии
Латифова Н.Ф.
(Азербайджанский Медицинский Университет, Баку, Азербайджан)
Резюме.
Цель работы: сравнительное изучение некоторых цитокинов (IL-6, IL-8, IL-10 и TNF-a) в сыворотке крови у больных сахарным диабетом 2-го типа на фоне изменения биохимических показателей начальной и терминальной стадии диабетической нефропатии.
Материалы и методы. Больные сахарным диабетом 2-го типа подразделены на 2 группы: 1-я - 21 больной, получившие медикаментозное лечение (начальная стадия диабетической нефропатии - консервативная группа), 2-я - 24 больных, которые регулярно подвергались гемодиализу («терминальная» стадия хронической болезни почек). В контрольную группу входили 17 практически здоровых доноров. Концентрации креатинина и мочевины в сыворотке крови были определены биохимическим методом с помощью набора реактивов «Lachema» (Чехия), концентрацию цитокинов IL-6, IL-8, IL-10 и TNF-a в сыворотке крови устанавливали иммуноферментным методом при помощи набора реактивов фирмы «Vector Best» (Россия). Статистическую значимость различий определяли методом ранговой вариационной статистики U-Mann-Whitney, с вычислением медианы (Me) и квартальных значений (Q1, Q3), с помощью статистического пакета IBM Statistics SPSS-21.
Результаты. При исследовании показателей, отображающих функцию почек, обнаружили значительное повышение креатинина мочевины в терминальной стадии в 2,8 и 7,9 раза, соответственно, относительно группы больных с начальной стадией и контрольной группы. При определении уровней провоспалительных цитокинов в группе с начальной стадией наблюдается статистически значительное увеличение содержания IL-8 и TNF-a в 1,7 (p<0,001) и 2,3 раза (p=0,006) по сравнению c контролем. В терминальной стадии также было выявлено более существенное повышение уровней IL-8 и TNF-a в 2,0 раза (p<0,001) и 4,6 раза (p<0,001) по сравнению с контролем, соответственно.
Заключение. Активация провоспалительных цитокинов у больных с диабетической нефропатией тесно связана с эндотелиальными поражениями почечных каналов, определяемыми повышенной концентрацией в крови креатинина и мочевины. Изучение цитокинового статуса позволяет говорить о значимости провоспалительных цитокинов в течении диабетической нефропатии, они могут быть применены для выбора наиболее оптимальной тактики лечения больных сахарным диабетом 2-го типа с нефропатией, профилактики развития почечной недостаточности.
Ключевые слова: диабетическая нефропатия; IL-6; IL-8; IL-10; TNF-a.
THE ROLE OF sOME cYTOKINEs IN DIABETic NEpHROpATHY
Latifova N.F.
(Azerbaijan Medical University, Baku, Azerbaijan)
Summary.
Aim: The aim of the work was a comparative study of certain cytokines (IL-6, IL-8, IL-10 and TNF-a) in blood serum of patients with type 2 diabetes amid a change in the biochemical parameters of the initial and terminal stages of diabetic nephropathy.
Material and methods. Type 2 diabetes patients are divided into 2 groups: 1) 21 patients who received medication (the initial stage of diabetic nephropathy - a conservative group), 2) 24 patients who underwent regular hemodialysis ("terminal" stage of chronic renal failure). The control group consisted of 17 healthy donors. Concentrations of creatinine and urea in blood serum were determined by the biochemical method using the "Lachema" reagents kit (Czech Republic), and the concentrations of IL-6, IL-8, IL-10, and TNF-a cytokines in blood serum were measured by enzyme immunoassay method using a set of reagents of "Vector Best" company (Russia). Statistical significance of differences was determined by the method of ranked variational statistics U-Mann-Whitney with the calculation of median (Me) and quarter values (Q1, Q3) with the help of statistical package IBM Statistics SPSS-21.
Results. The study of indicators representing renal function, revealed a significant increase in urea creatinine in the terminal stage by 2,8 and 7,9 times, respectively, relative to the group of patients with the initial stage and the control group. In determining the levels of pro-inflammatory cytokines there was a statistically significant increase in the concentration of IL-8 and TNF-a by 1,7 (p<0,001) and 2,3 times (p=0,006) in the group with the initial stage compared with the control values.
