Nghiên cứu một số đặc điểm lâm sàng, cận lâm sàng và nồng độ một số cytokin huyết tương trên bệnh nhân mắc bệnh gan mạn do rượu tt tiếng anh

THAI NGUYEN UNIVERSITY UNIVERSITY OF MEDICINE & PHARMACY LE QUOC TUAN STUDY OF CLINICAL AND SUBCLINICAL CHARACTERISTICS AND CYTOKINE LEVELS IN PATIENTS WITH ALCOHOLIC CHRONIC LIVER DISEASE Major: Internal Medicine ID: 97.20.107 DISSERTATION ABSTRACT THAI NGUYEN - 2018 Dissertation was completed at: Thai Nguyen University of Medicine & Pharmacy Advisors: Assoc.PhD Tran Viet Tu Assoc.PhD Nguyen Ba Vuong Reviewer 1: Assoc.PhD Reviewer 2: Assoc.PhD Reviewer 3: Assoc.PhD Dissertation will be defensed in front of dissertation’s university council at: h: 201 Held in: Thai Nguyen University of Medicine & Pharmacy The information from this thesis can be found at: - Vietnam National Library - Library of Thai Nguyen University - Library of Thai Nguyen University of Medicine & Pharmacy INTRODUCTION Alcohol Liver Disease (ALD) is the result of harmful alcohol abuse and prolonged exposure The first stage of ALD is asymptomatic, reversible if alcohol withdrawal occurs, but the later stages of ALD can not be reversed, usually resulting in death due to esophageal varices There is no radical treatment except liver transplantation It affect the quality of life of patients, but also have a great impact on the socio-economic development Studies show that altered immunity and inflammation are key factors contributing to the progression of ALD Mediators of the immune system, such as cytokines or inflammatory factors, are primarily involved in the stages of the disease In ALD, the use of chronic alcohol activates Kupffer cells through receptors, increases interleukin-1 (IL-1) production, and alpha tumor necrosis factor (TNF-α), contributes to confusion, hepatic dysfunction, necrotizing fasciitis, hepatic cellular dysfunction, progressive liver fibrosis, and cirrhosis Studies of alcoholic hepatitis patients showed TNF-α, IL-1, IL-8, leukemia, mononuclear activation and macrophage This further demonstrates that inflammation is a key factor in the progression of ALD Inflammation is a major factor contributing to the development of ALD, and therapies that inflammation are a reasonable strategy Understanding the role of some cytokines in ALD stages helps to detect new therapies that inhibit inflammation at an early stage and fibrosis in the later stages of the disease is actually beneficial to slow down progression of the disease In Vietnam, the increasing number of patients with alcoholic liver disease is a matter of concern and concern due to the increasing use of alcohol in Vietnam However, studies on the association of cytokines with clinical, subclinical and clinical characteristics in patients with alcoholic liver disease have not been studied by researchers For that reasons, we study: "Study of some plasma cytokines in patients with alcoholic liver disease" with the aim: Describe the clinical, subclinical characteristics and TNF-α, IL-12, IL-1β, TGF-β in plasma in patients with chronic liver disease caused by alcohol Analysis of the relationship between TNF-α, IL-12, IL-1β, TGF-β in plasma with clinical, subclinical and clinical features in patients with chronic liver disease caused by alcohol SCIENTIFIC SIGNIFICANCE Emphasizing the role of some cytokines in the diagnosis, prognosis, providing useful evidence is the scientific basis for the application of cytokine therapy in the treatment of alcoholic liver disease PRACTICAL SIGNIFICANCE Determination of TNF-α, IL-12, IL-1β, TGF-β levels in plasma in patients with alcoholic hepatitis and alcoholic cirrhosis Evaluate the relationship between these cytokines and some clinical and laboratory characteristics in patients with ALD SUMMARY OF NEW CONTRIBUTIONS OF DISSERTATION The first thesis studied cytokines in patients with ALD plasma Contributing additional information about the cytokine role in alcoholic liver disease is the scientific basis for the use of cytokine-based therapies for the treatment of alcoholic liver disease Suggestting use of biomarkers for clinical use to detect inflammation and fibrosis of the liver The layout of the dissertation: + The dissertation consists of 102 pages including of the following sections: the introduction (2 pages): chaper 1: overview (37 pages): chapter 2: objects and methods (14 pages): chapter 3: results (17 pages): chapter 4: discussion (22 pages): conclusions (2 pages): petition (1 pages) The dissertation consists of 52 tables, 12 pictures The theis references include 102 references consist of Vietnamese document, 95 English document + The three related articles to the dissertation have been published in the Vietnam Medical Journal Chapter OVERVIEW 1.1 Alcoholic liver disease Epidemiology: Alcohol abuse is prevalent throughout the world, with an estimated 18 percent of adults in the United States In 2010, alcoholic cirrhosis caused 493,300 deaths (accounting for 1% of total deaths) In the United States, the National Institute of Health estimates that in 2009, there were more than 31,000 deaths from cirrhosis and in which cirrhosis accounted for 48% of deaths The incidence of alcoholic liver disease is higher in areas with high levels of alcohol consumption per capita Areas with high rates of alcohol consumption and alcoholic liver disease include Eastern Europe, Southern Europe, and the United Kingdom Countries with large numbers of Muslims have the lowest rates of alcohol consumption and alcoholic liver disease The United States has an average consumption of 9.4 L/adult/year, compared with 13.4 L/year in England and 0.6 L/year in Indonesia 1.1.2 Clinical features, laboratory results of alcohol liver disease In most cases, the clinical is less or asymptomatic in the early stages and in the compensated period Clinical manifestations of ALD vary from asymptomatic or mild to fatal cirrhosis Therefore, the diagnosis is highly dependent on clinical signs, different tests and invasive or non-invasive techniques Typical ALD: - Anorexia, nausea, vomiting, discomfort, weight loss, abdominal pain and jaundice Fever sometimes up to 390C, 50% of cases - Examination: most have large liver, pain, one third of cases have large spleen - More likely: ascites, edema, hemorrhage, hepatic brain syndrome Symptoms of jaundice, ascites, and hepatic brain syndrome can be reduced by abstaining from alcohol If the patient continues to drink alcohol and poor nutrition can lead to repeated episodes with manifestations of decompensated cirrhosis, resulting in death Some patients with early signs of alcohol abuse such as salivary gland dysfunction, body weakness, malnutrition, may have peripheral neurological signs, but usually patients without symptoms and Reluctance to admit alcohol may be the cause of abnormal liver function During clinical examination of patients with cirrhosis, typical skin manifestations of liver disease include: cardiovascular disease, palmar edema and glossy tongue Jaundice, hepatic brachial syndrome, ascites and edema may also be seen in patients with endstage liver disease Consider ALD when patients have a history of excessive drinking ( > 40-50 g/day) and clinical abnormalities and abnormal test indices suggest liver damage However, when drinking history is often forgotten, it is often necessary to use indirect alcohol screening tools In patients with alcoholic liver disease, alcohol withdrawal symptoms, delirium, hypertension, mild fever, abdominal pain, paranoid hallucinations and hallucinations, have been reported after 72-96 hours of withdrawal AST/ALT > Increasing AST < 500 U/L, increasing ALT < 300 U/L Increasing GGT MCV > 100 fL Histopathology: Mallory hepatic degeneration, Mallory syndrome, giant mitochondria, inflammatory cell infiltration, liver fibrosis and fatty liver 1.4 Definitive diagnosis of alcoholic liver disease According to the guidelines of the American Liver Disease Research Association (AASLD - 2010): Diagnosis based on a history of alcohol use (screening alcohol use of the World Health Organization, AUDIT - WHO), clinical symptoms of liver disease, and abnormal liver enzymes Liver biopsy helps diagnose the cause, and identifies the stages of liver damage Observational studies showed that serum TNF-α levels as well as those of the liver increased in patients with alcoholic hepatitis, and were correlated with the severity of the disease Apply this scientific basis to use TNF-α inhibitor in the treatment of patients with ALD 1.5 The role of some cytokines in alcoholic liver disease Serum IL-12 levels are increased in patients with alcohol poisoning, alcoholic hepatitis, alcoholic cirrhosis IL-12 is highest in patients with alcoholic hepatitis and gradually decreases with alcohol abstinence TGF-β is central in chronic liver disease, which is related to the progression of the disease, from initial liver damage through inflammatory and fibrosis reactions leading to cirrhosis and hepatocellular carcinoma TGF-β activates the production of collagen from astrocytes Damage to the liver causes TGF-β to enhance astrocytomatic regulation and activate fibroblasts leading to a wound healing response, including myofibroblast and extracellular deposition Recognizing as a major profibrogenic cytokine, TGF-β signaling pathways are associated with the inhibition of progression of liver disease Numerous data indicate that the important role of IL-1β in alcoholic liver damage depends on the formation and activation of the inflammasome It relates to the progression of the disease Chapter MATERIAL AND METHODS 2.1 Focus group 2.1.1 The study group - 95 inpatients with ALD who were treated at the Gastrointestinal Department of Thai Nguyen Nation Hospital and 103 Military Hospital; 40 healthy students of Military Medical University - Time: From January 2015 to December 2015 Inclusion criteria * Study group: 95 inpatients had been diagnosed with ALD according to the guideline of the American Association for the Study of Liver Diseases (AASLD) 2010: The diagnosis of ALD is based on a combination of features, including a history of significant alcohol intake, clinical evidence of liver disease, and supporting laboratory abnormalities - The histological features of alcohol-induced hepatic injury vary, depending on the extent and stage of injury These may include steatosis (fatty change), lobular in-flammation, periportal fibrosis, Mallory bodies, nuclear vacuolation, bile ductal proliferation, and fibrosis or cirrhosis - Patients who agreed to take part in the research 12 Table 3.5 Evaluation of liver enzyme in patients with ALD Liver enzyme test Number (n=95) Ratio (%) Nomal 2,1 increasing 89 93,7 AST (U/L) ALT < 500 ≥ 500 4,2 198,19 ± 155,05 X ± SD Nomal 24 25,3 increasing 63 66,3 ALT (U/L) ALT < 200 ≥ 200 8,4 85,86 ± 71,06 X ± SD Nomal 2,1 GGT (U/L) increasing 93 97,9 749,10 ± 716,18 X ± SD The mean AST was 198,19 ± 155,05 U/L 77,1% of patients had increased ALT < 200 U/L The mean ALT was 85,86 ± 71,06 U/L The mean GGT was 749,10 ± 716,18 U/L Table 3.6 Histological findings in ALD Histological Findings in ALD Number (n=95) 21 Large-droplet fat Features of Small-droplet fat fatty liver 66 Mixed Steatosis grade Location fatty liver 5-33% 34-66% > 66% of Zone Zone Zone Ratio (%) 22,1 8,4 69,5 25 40 30 91 26,3 42,1 31,6 95,8 68 66 71,6 69,5 13 F0 F1 Fibrosis stage F2 (n=95) F3 F4 Significant fibrosis Fibrosis grade (≥ F2) (n=95) Severe fibrosis (≥ F3) Cirrhosis (F4) Lipogranuloma Foamy degeneration Hemosederosis Some indicators of Mallory-Denk histopathology Bodies (n=95) Megamitochondria Eosin hepatocellular change 14 20 25 24 12 14,7 21,1 26,3 25,3 12,6 61 64,2 36 12 80 54 37,9 12,6 9,5 84,2 56,8 61 64,2 59 62,1 60 63,2 The grade of steatosis of 34%-66% accounted for 42,1%, the fatty liver zone accounted for 95,8% Stage of fibrosis F2 accounted for 26,3% Foamy degeneration accounted for 84,2%, the megamitochondria accounted for 64,2%, the Mallory body accounted for 60.2% Significant stage of fibrosis (≥ F2) accounted for 64,2% 14 Table 3.8 Results of TNF-α, IL-12, IL-1β, TGF-β indicators in patients with ALD and the controls Cytokine indicators TNF-α (pg/mL) IL-12 (ng/L) IL-1β n 95% CI Median Study subjects 95 110,61 - 326,42 173,64 Controls 153,71 - 166,71 158,23 24,45 - 32,10 27,47 40 Study subjects 95 Controls 40 Study subjects 95 - 4,00 13,42 - 15,34 14,36 < 0,001 Controls (ng/L) < 0,001 < 0,001 (ng/L) TGF-β p 40 Study subjects 95 3,19 - 3,30 3,19 1126,43 - 1320,91 1191,46 < 0,001 Controls 40 79563,90- 666819,53 110829,44 There was a statistically significant decrease in the plasma TGF-β in patients with alcoholic liver disease as compared to controls There was a statistically significant increase in the plasma TNF-α, IL-12, IL-1β in patients with alcoholic liver disease as compared to controls 15 3.2 The relationship between levels of TNF-α, IL-12, IL-1β, TGF-β in plasma with clinical, subclinical features in patients with chronic liver disease caused by alcohol Table 3.14 Relationship between TNF-α in plasma with histological findings in ALD Histological findings in ALD 95% CI Median F0 14 146,37 - 251,43 164,17 F1 20 145,81 - 190,02 155,97 F2 25 147,50 - 185,40 166,71 F3 24 149,76 - 158,80 153,72 F4 12 154,28 - 312,77 168,12 Disease Hepatitis 83 151,74 - 166,71 157,10 stage Cirrhosis 12 152,59 - 362,41 168,12 Fibrosis stage TNF-α n (pg/mL) The median TNF-α decreased in the hepatitis group (157,10 pg/mL) was lower than in the cirrhosis group (168,12 pg/mL), the difference was significant (p < 0,05) p > 0,05 < 0,05 16 Table 3.26 Relationship between IL-1β in plasma with histological findings in ALD Histological findings in n ALD Median F0 14 11,30 - 17,65 15,55 F1 20 10,88 - 19,28 16,11 F2 25 11,42 - 16,60 14,09 F3 24 10,60 - 15,23 13,22 F4 12 11,16 - 38,06 13,81 Disease Hepatitis 83 13,21 - 15,89 14,36 stage Cirrhosis 12 11,16 - 27,61 13,81 Fibrosis stage IL-1β 95% CI (ng/L) p > 0,05 < 0,05 The median IL-1β in the cirrhosis group (13,81 ng/L) was lower than in the hepatitis group (14,36 ng/L), the difference was significant (p < 0,05) Table 3.31 A Relationship between TGF-β in plasma with histological findings in ALD Histological findings in ALD TGF-β (ng/L) Features of fatty liver Steatosis grade n Largedroplet fat Smalldroplet fat 95%CI Median 988,42 - 1542,33 1246,59 1119,54 - 1460,42 1289,92 p 21 Mixed 66 1083,58 - 1320,91 1169,89 Mild 25 1119,54 - 1460,42 1246,59 Moderate 40 1050,03 - 1474,32 1221,43 > 0,05 > 0,05 17 Severe 30 1059,61 - 1344,88 1136,33 No - 1089,58 Yes 91 1138,30 - 1320,91 1208,24 No 27 1059,61 - 1459,97 1154,26 Yes 68 1119,54 - 1344,88 1199,85 No 29 1119,54 - 1492,30 1270,57 Yes 66 1083,58 - 1321,09 1169,89 No 86 1119,54 - 1342,48 1181,87 Yes 1049,21 - 1474,32 1246,59 Foamy No 36 1229,59 - 1512,69 1331,70 degeneration Yes 59 1049,21 - 1191,46 1124,34 No 15 1145,91 - 1491,11 1239,40 Yes 80 1091,11 - 1344,88 1163,27 Mallory-Denk No 41 1131,53 - 1343,68 1208,24 Bodies Yes 54 1069,12 - 1370,26 1181,87 No 34 1018,86 - 1460,42 1163,27 Yes 61 1126,43 - 1344,88 1208,24 No 35 1232,21 - 1491,11 1342,48 Yes 60 1041,64 1210,07 1121,94 Zone Zone Zone Lipogranuloma Hemosederosis Megamitochondria Eosin hepatocellular change - > 0,05 > 0,05 > 0,05 > 0,05 > 0,05 > 0,05 > 0,05 > 0,05 < 0,05 The median TGF-β in the Eosin hepatocellular change group (1121,94 ng/L) was lower than in the without Eosin hepatocellular change group (1342,48 ng/L), the difference was significant with p < 0,05 18 Table 3.32 A Relationship between TGF-β in plasma with histological findings in ALD Histological findings in ALD TGF-β (ng/L) Fibrosis stage Disease stage n F0 14 95%CI 1145,91 - 1512,69 Median 1084,38 F1 20 1062,01 - 1460,42 1136,33 F2 25 1038,04 - 1581,31 1172,28 F3 24 1016,46 - 1344,88 1289,92 F4 12 997,28 - 1529,47 1290,94 Hepatitis 83 1141,12 - 1325,70 1210,64 Cirrhosis 12 997,28 - 1529,47 1084,38 p < 0,05 < 0,05 There was a relationship between TGF-β in plasma with disease stage and fibrosis stage in ALD, the difference was significant with p < 0,05 Chapter DISCUSSION 4.1 Clinical, subclinical characteristics and TNF-α, IL-12, IL-1β, TGF-β in plasma in patients with chronic liver disease caused by alcohol 4.1.1 General characteristics Characteristics of age Our results showed that the age group of 45-59 were the most common 50,5% the mean age of the group was 50,65 years, our results was also similar to the authors, most alcoholism were at working age, so alcoholism greatly affected the socio-economic development Characteristics of sex 19 There were 95 male patients and no female patients, because of the collection of data in military hospital The results of the study showed that the proportion of women with ALD in Vietnam was lower than in foreign country 4.1.2 Clinical features The most common clinical symptoms were fatigue (84,2%), jaundice (66,3%), anorexia (64,2%), enlarged liver (63,2%) Symptoms of fatigue, insomnia, poor appetite, jaundice, abdominal pain, gastrointestinal disorders are common symptoms with high rates 4.1.3 Subclinical characteristics 93,7% of patients had an increasing AST but less than 500 U/L The mean AST was 198,19 ± 155,05 U/L 66,3% of patients had increasing ALT but less than 200 U/L The mean ALT was 85,86 ± 71,06 U/L 97,9% of patients had a increasing GGT The mean GGT were 749,10 ± 716,18 U/L In this study, most of patients had fatty liver According to the documents, about 90% of people drinking alcohol with fatty liver - Mixed liver fatty was commonly seen in the study subjects (69.5%) According to the documents, the type of large droplet fatty or mixed liver fatty was commonly seen in alcoholic fatty liver - Steatosis grade: the results of our study showed that the moderate fatty liver was higher proportion than the mild and severe fatty liver The steatosis zone accounted for 95.8% - Our results showed that the foamy degeneration accounted for 84,2%), megamitochondria accounted for 62,1%, Mallory body accounted for 64,2% were common histological features According to the medical documents, Mallory body (found in 76% of ALD 20 patients), foam degeneration, megamitochondria were histologic features in ALD patients Our study showed that liver fibrosis F2 (26.3%) and F3 (25.3%) accounted for the highest proportion, and fibrosis F4 accounted for the lowest proportion Of the 95 subjects, the majority of the study subjects were alcoholic hepatitis, accounting for 87.4% Significant levels of liver fibrosis accounted for 62.1% 4.1.4.Characteristics of TNF-α, IL-12, IL 1β, TGF- β Of the 95 patients studied, plasma TNF-α median was 173,64 pg/mL; plasma IL-12 median was 27,47 ng/L; plasma IL-1β median was 14,36 ng/L and plasma TGF-β median was 1191,46 ng/L Of the 40 controls, plasma TNF-α median was 158,23 pg/mL; Plasma IL-12 median was 4,0 ng/L; plasma IL-1β median was 3,19 ng/L; plasma TGF-β median was 110829,44 ng/L The cytokine levels in our study group was very high and nonstandard delivery, so we used the median for comparison between the study groups and control groups as well as for the relationship analysis 4.2 The relationship between levels of TNF-α, IL-12, IL-1β, TGF-β in plasma with clinical, subclinical features in patients with chronic liver disease caused by alcohol 4.2.1.TNF-α TNF-α can play an independent role in alcoholic liver disease by promoting the hepatopancreas process Studies show that alcohol increases the sensitivity of the hepatocyte to the cytokine's toxic effects Of the cytokines identified in alcoholic liver disease, TNF-α was most closely related to the severity of the disease In patients 21 with alcoholic hepatitis treated, improvement in clinical presentation is associated with decreased cytokine levels in the blood In addition, TNF-α inhibitors have also been shown to be effective in the treatment of alcoholic hepatitis The results of our study showed that TNF-α was significantly higher in the plasma of the control group than in the control group The difference was statistically significant with p < 0,001 This result is consistent with González-Reimers et al., Mortensen, ZuwaaJagieo When analyzing the association between TNF-α levels and clinical and subclinical features, we did not find out much association TNF-α levels was related to the disease stage, TNF-α median in the alcoholic cirrhosis group (168,12 pg/mL) was higher than those in the alcoholic hepatitis group (157,10 pg/mL), with p < 0,05 4.2.2 IL-1β IL-1β plays an important role in inflammation in alcoholic liver disease, which is a major factor in inflammation, fat degeneration and hepatocellular injury Our results: plasma IL-1β median was higher in the study group compared with the control group, the difference was statistically significant with p < 0,001 Similar to Petrasek (2012), Tung et al (2012), Naoko et al (2013) When analyzing the relationship between plasma IL-1β concentrations and glucose The level of IL-1β in the group of alcoholic hepatitis (14,36 ng/L) was higher than in the alcoholic cirrhosis group (13,81 ng/L), the difference was statistically significant with p < 0,05 This result is consistent with that of Tung et al 22 4.2.3.TGF-β Astrocytes in the liver directly affect the fibrosis process by increasing scar formation The most potent form of collagen I production is TGF-beta, derived from both paracrine and autocrine sources; TGF-beta also stimulates the production of fibroneectin and proteoglycans Other factors that stimulate collagen I through astrocytes include retinoids, angiotensin II, IL-1β, TNF-α, and acetaldehyde However, the strongest is TGF-β Our results: TGF-β levels in plasma were significantly lower in the study group than in the control group with p < 0,001 Our results were similar to Szczerbińska et al (2015), Neuman In our study, TGF-β was correlated with disease stage and fibrosis stage: Median TGF-β levels in F3-F4 fibrosis group (1289,92 ng/L – 1290,94 ng/L) was significantly higher than that of F0-F1 liver fibrosis (1084,38 – 1136,33 ng/L) and the difference was statistically significant with p < 0,05 This finding is consistent with the results of Lavallard et al 4.2.4.IL-12 Results of our study: plasma IL-12 concentration was higher in the study group than control group with p < 0,001 Similar to author Tung et al (2012), Sowa In conclusion, Tung's research has demonstrated that levels of serum IL-12 reflect different stages of alcoholic liver disease and may indicate persistent alcohol consumption It has the potential to become a biomarker of alcoholic liver disease 23 In our study, there was no significant association between cytokine levels and clinical and subclinical characteristics But, it was just initial results; moreover, clinical and laboratory findings in patients with non-specific alcoholic liver disease In order to have more accurate, objective conclusions, it is necessary to study in a larger scale CONCLUSION Clinical, subclinical characteristics and TNF-α, IL-12, IL1β, TGF-β in plasma in patients with chronic liver disease caused by alcohol The age group was at least 30 years old, the highest was 76 years old and the average age was 50,65 years The most common clinical symptoms were fatigue (84,2%), jaundice (66,3%), anorexia (64,2%), enlarged liver (63,2%) Average AST was 198,19 ± 155,05 U/L, mean ALT was 85,86 ± 71.06 U/L, average GGT was 749,10 ± 716,18 U/L Mixed fatty accounted for the highest proportion of 69,5% Liver fatty of 34-66% accounted for 42,1% Zone fatty accounted for the highest rate of 95.8% Mallory was 64.2%, giant 62.1%, and eosinophilus were 63.2% Metavir Fibrosis Stage F2 and F3 stage accounted for 26.3%, 25.3% Histological results were mostly fatty liver and commonly significant liver fibrosis stage (64,2%) The patients had histological features of ALD such as alcoholic foamy degeneration (84,2%), megamitochondria (62,1%), Mallory body (64,2%) 24 The plasma TNF-α median was 173,64 pg/mL; plasma IL-12 median was 27,47 ng/L; plasma IL-1β median was 14,36 ng/L and plasma TGF-β median was 1191,46 ng/L The results of control group: plasma TNF-α median was 158,23 pg/mL; plasma IL-12 median was 4,0 ng/L; plasma IL-1β median was 3,19 ng/L; plasma TGF-β median was 110829,44 ng/L - TGF-β in the plasma in the study group was lower than in the control group TNF-α, IL-1β and IL-12 in the plasma in the study group was higher than in the control group The difference was statistically significant with p < 0,001 The relationship between levels of TNF-α, IL-12, IL-1β, TGF-β in plasma with clinical, subclinical features in patients with chronic liver disease caused by alcohol TNF-α was associated with the disease stage, TNF-α median in the alcoholic cirrhosis group (168,12 pg/mL) were higher than in the alcoholic hepatitis group (157,10 pg/mL), with p < 0,05 There was a correlation between plasma IL-1β concentrations and glucose Plasma IL-1β median in the alcoholic cirrhosis group (13,81 ng/L) were lower than that in the alcoholic hepatitis group (14,36 ng/L), the difference was statistically significant with p < 0,05 There was a correlation between TGF-β levels in plasma and eosinophilia There was a correlation between TGF-β with disease stage and fibrosis stage: plasma TGF-β median in F3-F4 liver fibrosis group (1289,92 ng/L - 1290,94 ng/L) was higher than F0-F1 liver fibrosis group (1084,38 -1136,33 ng/L) and plasma TGF-β median in the alcoholic cirrhosis group (1084,38 ng/L) was lower than in the 25 alcoholic hepatitis group (1210,64 ng/L), the difference was statistically significant with p < 0,05 RECOMMENDATIONS Cytokines play an important role in the stages of alcoholic liver disease, so it is possible to use as a marker to predict alcoholic liver disease PUBLISHED RELATED TO THE DISSERTATION Le Quoc Tuan, Tran Viet Tu, Nguyen Ba Vuong (2018), "Clinical characteristics and some biochemical indicators in plasma in patients with alcoholic liver disease", Viet Nam Journal of Medicine, No 2, June 2018, volume 467, pp.92-95 Le Quoc Tuan, Tran Viet Tu, Nguyen Ba Vuong (2018), "Characteristics of liver histopathology in patients with alcoholic liver disease", Viet Nam Journal of Medicine, No 2, June 2018, volume 467 pp.51-55 Le Quoc Tuan, Tran Viet Tu, Nguyen Ba Vuong (2018), "Research on some plasma cytokines in patients with alcoholic liver disease", Viet Nam Journal of Medicine, No 2, June 2018, volume 467, pp.129-132 Le Quoc Tuan (2018) “Role of cytokines in alcoholic liver Disease”, Gut; 67(Suppl 2): A1 – A118 ... patients had fatty liver According to the documents, about 90% of people drinking alcohol with fatty liver - Mixed liver fatty was commonly seen in the study subjects (69.5%) According to the documents,... the type of large droplet fatty or mixed liver fatty was commonly seen in alcoholic fatty liver - Steatosis grade: the results of our study showed that the moderate fatty liver was higher proportion... information about the cytokine role in alcoholic liver disease is the scientific basis for the use of cytokine-based therapies for the treatment of alcoholic liver disease Suggestting use of biomarkers