Study On The Relationship Among Chronic Inflammatory Markers,Thyroid Hormones,Thyroid Stimulating Hormones And Non-alcoholic Fatty Liver Disease

Objective:The incidence of non-alcoholic fatty liver disease?NAFLD?is increasing every year with a trend of younger people,which is the main pathogenesis of liver enzyme index anomalies and occult cirrhosis.At the same time,the relationship between NAFLD and the cardiovascular system disease,chronic kidney disease,diabetes of type 2 is closely as a serious public health problem.In the early stage of NAFLD,there was no obvious clinical manifestation,and the incidence was insidious and lacking specificity,which was usually found in the medical examination or the visit to the hospital.At present,the treatment of NAFLD is lack of effective means,mainly depending to etiology prevention.Mild and moderate liver steatosis is reversible,therefore epidemiological studies of NAFLD has important practical significance.Besides the traditional risk factors of NAFLD,in recent years it found that some inflammatory markers such as white blood cell count,neutrophil count were associated with the occurrence of NAFLD.So a large sample size of epidemiological study is urgently needed.In addition,studies on the relationship between thyroid hormones,thyroid hormones and NAFLD were slightly different in the normal thyroid function population.Therefore,the healthy check-up crowd clinical data on the basis of large sample size were retrospectively analyzed,aiming to explore the potential risk factors of NAFLD and provide early prevention strategies from the perspective of health management of NAFLD.Methods:A retrospective analysis was conducted on the clinical indicators of the patients who underwent routine physical examination at the health management center of the hospital from January 2015 to December 2015.Using the pre-designed Excel spreadsheet,the relevant analysis indicators of the eligible study subjects were extracted from the hospital's HIS system after strict inclusion and exclusion criteria.All subjects were required to undergo a physical examination in the early morning after 12 hours of fasting,including a healthy self-test questionnaire,anthropometric examination,clinical and biochemical indicators.The questionnaire includes diet,life history,disease history and medication history.Record the demographic characteristics of the subjects,including basic information such as name,gender and age in detail.Anthropometric tests include height,weight,body mass index?BMI?,systolic blood pressure?SBP?,and diastolic blood pressure?DBP?.Clinical and biochemical indexes including white blood cell count?WBC?,neutrophil counts?NC?,alanine aminotransferase?ALT?,aspartate aminotransferase?AST?,alkaline phosphatase?ALP?and gamma glutamine transferase?GGT?,triglycerides?TG?,total cholesterol?TC?,high-density lipoprotein cholesterol?HDL-C?,low density lipoprotein cholesterol?LDL-C?,serum creatinine?Cr?,blood urea nitrogen?BUN?,fasting plasma glucose?FPG?,Serum free triiodothyroxine?FT3?,free thyroxine?FT4?and serum thyrotropin?TSH?.The normal reference ranges of FT3,FT4 and TSH are:2.63-5.70 pmol/L,9.01-19.05 pmol/L,0.35-4.94 mIU/L.The diagnosis of NAFLD was performed by color doppler ultrasonography.SPSS 17.0 statistical software was used for statistical analysis.For the measurement data,if data met normal distribution,with homogeneity of variance,describe with the mean±standard deviation and hypothesis testing using parametric tests,the main method of group t test,variance analysis etc.;where the data did not meet normal distribution,heterogeneity of variance,describe using median and interquartile range,hypothesis tests using non-parametric tests,between the two groups were compared using the Mann-Whitney test,Kruskal-Wallis test was used to compare multi-groups.For count data were compared using the chi-square test.Spearman rank correlation analysis was used for correlation test.Logistic regression model was used for multivariate analysis.The predictive value of WBC and NC on NAFLD was determined by using the ROC curve.The statistical test level was?=0.05.The significance level was P<0.05.The interaction of statistics was analyzed by multiplication effect model.Results:1.A total of 30,676 study subjects were included in the final study,of which12,664 met the diagnostic criteria of NAFLD.The prevalence was 41.28%.We defined NAFLD group and non-NAFLD group.The differences between WBC and NC in NAFLD group and non-NAFLD group were statistically significant.2.WBC and NC were divided into quartile.With the increasing of WBC and NC,the prevalence of NAFLD increased.Among the whole population,the prevalence rate of NAFLD in WBC 1,2,3 and 4 was 28.00%,37.41%,44.84%and 54.93%,respectively with the increasing trend??²=1239.228,P<0.001?.Among males,the prevalence rate of NAFLD was 41.07%,51.28%,58.42%and 67.17%??²=589.297,P<0.001?.Among females,the prevalence rate of NAFLD was 18.05%,23.00%,26.74%,and 34.24%,respectively,respectively??²=258.410,P<0.001?.Among the whole population,the prevalence rate of NAFLD in NC 1,2,3 and 4 was 30.42%,39.48%,44.42%and 50.65%,respectively??²=689.137,P<0.001?.Among the males,the prevalence rate of NAFLD was 43.39%,53.40%,58.86%and 64.51%,respectively??²=380.962,P<0.001?.Among females,the prevalence rate of NAFLD was 19.62%,23.57%,26.16%and 30.64%,respectively??²=123.859,P<0.001?.3.The results of single factor analysis showed that the risk of NAFLD increased by1.452 and 1.315 times respectively for each increment of white blood cell count and neutrophil count.4.Adjustment for age,gender,BMI,WC,SBP,DBP,FPG,TG,TC,HDL-C,LDL-C,ALT,AST,ALP,GGT,BUN and Cr,with the rising level of WBC,the odds ratio?95%CI?of NAFLD were 1.000?reference group?,1.192?1.094,1.094?,1.094?1.209,1.434?and 1.209?1.411,1.411?(P _{for trend}<0.001).With the increasing level of NC,the ratio of NAFLD?95%CI?was 1.000?reference group?,1.147?1.053,1.248?,1.242?1.141,1.353?and 1.299?1.193,1.416?(P _{for trend}<0.001).5.The area of ROC curve predicted by WBC for NAFLD was 62.2%with an optimal threshold of6.33x10⁹/L,The corresponding sensitivity and specificity were 60.4%and 57.3%respectively.The area of ROC curve predicted by NC for NAFLD was 58.9%with an optimal threshold of 3.50 x 10⁹/L.The corresponding sensitivity and specificity were59.9%and 53.2%respectively.6.From the total population and a normal thyroid function levels,we selected 1773 cases.And 638 cases met the diagnosis of NAFLD.The prevalence of NAFLD was 35.98%,which is divided into NAFLD group and non NAFLD group for comparison.The results showed that the serum FT4 level was not significantly different between the two groups in the general population,while the TSH and FT3 levels in NAFLD group were significantly higher than that in the non-NAFLD group.Subgroup analysis was conducted according to gender.The results showed that the serum TSH and FT4 levels were not significantly different between the two groups in the male population,while the FT3 level in NAFLD group was significantly higher than that in the non-NAFLD group.In the female population,the serum TSH,FT3 and FT4 levels were not significantly different between the two groups.7.With the increasing of serum TSH level,the prevalence of NAFLD showed an increasing trend.After controlling the influence of gender and age,the increase trend was still statistically significant(P _{for trend}=0.007).In addition,with the increasing of serum FT3 level,the prevalence of NAFLD also showed an upward trend with a statistical significance(P _{for trend}<0.001).With the increasing of FT4level,there was no significant change in the prevalence of NAFLD.8.Spearman rank correlation was used to analyze the level of the thyroid and metabolic parameters.The results showed that serum TSH level was positively correlated with BMI,WC,FPG,TC,AST,GGT and Cr,and negatively correlated with HDL-C.Serum FT3 levels were positively correlated with BMI,WC,SBP,DBP,FPG,TG,ALT,AST,ALP,GGT,BUN and Cr,and negatively correlated with HDL-C There was no significant correlation between serum FT4 level and other indicators.9.Multivariate logistic regression analysis showed that the elevated TSH and FT3 levels were independent influences of NAFLD in the general population?TSH,OR:1.108,95%CI:1.056-1.398,P=0.024,FT3,OR:1.238,95%CI:1.114-1.376,P=0.000?.While in the male population,only the elevated FT3 level was independent influence of NAFLD?OR:1.192,95%CI:1.032-1.376,P=0.017?.10.The results of interaction analysis showed that serum FT3 levels and metabolism-related components in the normal thyroid population included BMI,WC,FPG,TG and LDL-C,which had no interaction with NAFLD.The serum TSH level had no interaction with these metabolic indicators.The confidence interval of each interaction term OR value contained 1,P>0.05.Conclusion:1.After adjusting the influence of confounding factors,the count of white blood cells and neutrophils were positively correlated with NAFLD.2.White blood cell count and neutrophil count combined with body mass index,waist circumference,fasting blood glucose,triglyceride these metabolic indicators for the screening of NAFLD has a high predictive value.3.In the normal thyroid function group,serum thyroid hormone and thyrotropin levels were positively correlated with NAFLD,independent of BMI,WC,SBP,DBP,FPG,TG,TC,HDL-C,LDL-C,ALT,Except AST,ALP,GGT,BUN and Cr.4.In the normal thyroid male population,elevated serum FT3 levels are independent factors in the occurrence of NAFLD.