| Objectives:By monitoring the changes in peripheral blood immune indicators of the study subjects,comparing the differences in peripheral blood immune cells and cytokines between patients with metabolic related fatty liver disease and healthy individuals,and exploring whether MAFLD patients have immune dysfunction.Analyze the correlation between the progression of MAFLD and changes in peripheral blood immunological indicators,and explore the clinical significance of immune monitoring in the occurrence and development of MAFLD.Methods:A total of 128 patients who visited our hospital from November 2021 to December 2022 were collected.The basic information,clinical data,blood biochemical indexes,two-dimensional abdominal gray scale ultrasound and the results of liver instantaneous elastic hardness test of the included patients were sorted.T cells,B cells,NK cells,Th17 cells,Treg cells and 12 cytokines in peripheral blood were detected by Flow cytometry immunofluorescence sorting,and T cell activation was measured.The subjects were divided into healthy control group and MAFLD group according to the international expert consensus on MAFLD name change in2020.Independent sample T test and Wilcoxon Mann-Whitney test were used to analyze the differences of peripheral blood immune cells and cytokines between the two groups.MAFLD patients were divided into mild fatty liver group,moderate fatty liver group,and severe fatty liver group based on the abdominal two-dimensional gray scale ultrasound CUS score.Univariate analysis of variance and Kruskal Wallis test were used to analyze the differences in peripheral blood immune cells and cytokines among the three groups.Spearman correlation and multiple logistic regression were used to explore the relationship between different degrees of fatty liver and changes in peripheral blood immune indicators in MAFLD patients.Results:1.According to the international expert consensus on the renaming of MAFLD in 2020,the study subjects were divided into a healthy control group of 40 patients(7males and 33 females,with an average age of 34.0±13.38 years),and a MAFLD group of 88 patients(58 males and 30 females,with an average age of 35.44±8.49years).Based on the abdominal two-dimensional grayscale ultrasound CUS score,MAFLD patients were divided into three groups:21 mild fatty liver patients(9 males and 12 females,with an average age of 34.80±10.35 years),48 moderate fatty liver patients(35 males and 13 females,with an average age of 38.22±7.87 years),and 19 severe fatty liver patients(14 males and 5 females,with an average age of32.00±9.25 years).2.Comparison of general information:Body weight,waist circumference,BMI,HOMA-IR,blood glucose,TG,LDL-C,UA,ALT,gamma-GGT and ALP 2 hours after meal in MAFLD group were significantly higher than those in healthy control group,while HDL-C,ALB,TB and IB were significantly lower than those in healthy control group.There were statistically significant differences in gender,history of hypertension,history of diabetes and history of dyslipidemia between the two groups(P<0.05),while there were no statistically significant differences in age,FPG,Hb A1c,TC,AST and DB between the two groups.Weight,waist circumference,BMI,HOMA-IR,UA,AST,ALT,γ-GGT was significantly higher than the moderate and mild fatty liver groups,while TG in the moderate fatty liver group was significantly higher than that in the mild and severe fatty liver groups.HDL-C in the mild fatty liver group was significantly higher than that in the moderate and severe fatty liver groups,and the differences were statistically significant(P<0.05).3.Comparison of immune cells between MAFLD group and healthy group:The absolute number of neutrophils,eosinophils,proportion and absolute number of basophils,absolute number of monocytes,absolute number of lymphocytes,absolute number of T cells,absolute number of Tc/Ts,absolute number of Helper T cells,proportion and absolute number of B cells in the MAFLD group were significantly higher than those in the healthy control group,while the proportion of NK cells was significantly lower than that in the healthy control group,with statistical significance(P<0.05);There was no statistically significant difference in the proportion of neutrophils,eosinophils,monocytes,T cells,Tc/Ts,Helper T cells,Th/Ts,and NK cells between the two groups.4.Comparison of immune cells among MAFLD subgroups:The proportion of monocytes,absolute number of monocytes,proportion of B cells,and absolute number of B cells in the severe fatty liver group of MAFLD patients were significantly higher than those in the moderate and mild fatty liver groups,and the differences were statistically significant(P<0.05).There were no statistically significant differences in the proportion and absolute number of neutrophils,eosinophils,basophils,lymphocytes,T cells,Tc/Ts,Helper T cells,Th/Ts,NK cells among the three groups.5.Comparison of T cell activation:The CD4~+Th17/Treg levels in the MAFLD group were significantly lower than those in the healthy control group,with a statistically significant difference(P<0.05).There was no statistically significant difference in CD4~+Th17/Treg levels among the three groups in the MAFLD.There was no statistically significant difference in other T cell activation indicators.6.Comparison of cytokines:IL-5 in MAFLD group was significantly higher than that in healthy control group,while the proportions of IL-6,IL-8,IL-12p70,TNF-α,IFN-α,IL-4,IL-10 and IL-10/IL-17 in MAFLD group were significantly lower than those in healthy control group,with statistical significance(P<0.05).There were no significant differences in IL-1β,IL-2,IL-17 and IFN-γbetween the two groups.IL-1βin severe fatty liver group of MAFLD patients Significantly higher than the moderate and mild fatty liver groups,and the levels of IL-12p70 and IL-10 in the mild fatty liver group were significantly higher than those in the moderate and severe fatty liver groups,with statistically significant differences(P<0.05).There were no significant differences in IL-2,IL-5,IL-6,IL-8,IL-17,TNF-α,IFN-α,IFN-γ,IL-4 and IL-10/IL-17 ratio among the three groups.7.Spearman correlation analysis:The degree of fatty liver in MAFLD patients was positively correlated with the absolute number of monocytes(r=0.345,P=0.006),the proportion of B cells(r=0.407,P=0.002),the absolute number of B cells(r=0.474,P<0.001)and IL-1β(r=0.217,P=0.044).It was negatively correlated with IL-12p70(r=-0.264,P=0.013)and IL-10(r=-0.243,P=0.023).No correlation was found with other immune cells and cytokines.8.Multiple logistic regression analysis:BMI,ALT,absolute number of neutrophils are the influencing factors for the progression of MAFLD(P<0.05).Conclusion:1.MAFLD patients are closely related to obesity,glucose,lipid,purine,and bilirubin metabolism disorders.2.MAFLD patients have high expression of myeloid immune cells(absolute number of neutrophils,absolute number of eosinophils,proportion and absolute number of basophils,absolute number of monocytes)and lymphoid immune cells(absolute number of lymphocytes,absolute number of T cells,absolute number of Tc/Ts,absolute number of Th cells,proportion and absolute number of B cells),while low expression of NK cell ratio and CD4+Th17/Treg,and monitoring of peripheral blood routine Lymphocyte subpopulations and T cell activation can evaluate the immune disorders in MAFLD in vivo.3.MAFLD patients have high expression of pro-inflammatory cytokine IL-5,while low expression of anti-inflammatory cytokines IL-4,IL-10,and IL-10/IL-17.MAFLD patients have cytokine imbalance.4.The progression of MAFLD is related to the absolute number of peripheral blood monocytes,proportion of B cells,absolute number of B cells,and pro-inflammatory cytokine IL-1βThere is a positive correlation and a negative correlation with the anti-inflammatory cytokine IL-10.4.Monitoring the above indicators can predict the progress of MAFLD.5.BMI,ALT,absolute number of neutrophils are factors affecting the progression of MAFLD. |
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