Association Between Phthalate Ester Exposure And Nonalcoholic Fatty Liver Disease In A Group Of People

Objective:Animal experiments have shown that Phthalic Acid Esters(PAEs)may cause chronic fatty lesions in the liver.The purpose of this study was to explore the correlation between the exposure level of diesters of phthalate and nonalcoholic fatty liver disease(NAFLD)on the basis of understanding the exposure level of PAEs and the prevalence of nonalcoholic fatty liver disease in the occupational population of our province.It provides theoretical support for the later systematic study on the mechanism of liver injury in Di(2-ethylhexyl)Phthalate(DEHP),and also provides the basis for the preventive measures of NAFLD in the future.Methods:Part 1:The questionnaire survey method was used to investigate the demographic characteristics and behavioral habits of the 3501 physical examination workers in the same coal group.The professional medical personnel of the affiliated hospitals of the Coal Group evaluated the blood glucose-related indicators,triglyceride(TG),total cholesterol(CHOL),and Density lipoprotein(HDL)and low-density lipoprotein(OX-LDL)were medically tested and diagnosed according to the diagnostic criteria of alcoholic liver disease and NAFLD.According to different data types,the corresponding statistical methods were used to analyze the demographic characteristics,behavioral habits and blood lipid-related biochemical indicators of the physical examination population;Logistic regression method was used to perform multivariate analysis on the relevant indicators with statistically significant differences in the univariate analysis.Part 2:In this study,a 1:1 matched case-control study was performed.Ninety-five pairs of age-and sex-matched pairs of NAFLD patients and controls were analyzed for urinary PAEs metabolites by high performance liquid chromatography tandem mass spectrometry(HPLC-MS)and Wilconxon paired-rank test was used.Statistical analysis.They are Monomethyl phthalate(MMP),Monoethyl phthalate(DEP),Mono-n-butyl phthalate(MBP),and Ortho-phthalate.Monobenzyl phthalate(MBz P),Mono(2-ethylhexyl)phthalate(MEHP),Monodecyl monophthalate(Mono-Isn-butyl phthalate(MNP),mono-iso-butyl phthalate(MOP).The univariate analysis was performed on the general conditions,behavioral habits,and lipid-related parameters of the matched population.The statistically significant differences in the above analysis were compared with those of the Wilcoxon paired-rank test to the multivariate conditional logistic regression model.analysis.Results :1.The detection rate of NAFLD of the employees of the Coal Group was as high as 31.7%.Univariate NAFLD analysis showed that age,sex,BMI index,marital status,intensity of physical activity,past medical history hypertension diabetes,taste tendency of edible oil,sleep self-evaluation,and related lipid levels in the physical examination population in the case and non-case groups The differences of the indicators were statistically significant(P<0.05).After adjusting the above variables into Logistic regression model,age groups were 5-45 years old and ? 45 years old(OR=1.28,1.58,P<0.05),BMI index(OR=1.68,P<0.05),and diabetes mellitus.(OR=1.79,P<0.05),serum triglyceride content(OR=1.37,P<0.05)and low-density lipoprotein content(OR=1.74,P<0.05)were statistically different.2.In this experiment,high performance liquid chromatography tandem mass spectrometry(HPLC-MS)was used to determine urine PAEs metabolites.The regression equation correlation coefficients were all higher than 0.97.The detection limits were in the range of 0.1-1.0 pg/?L and metabolite MEHP detection rates.At 83.7%,the detection rate of the remaining metabolites was more than 85%.The median content of the seven metabolites detected in the case group was MMP 2.92 pg/ ?L,MEP 2.69 pg/ ?L,MBP 23.93 pg/ ?L,MBzP 0.84.Pg/ ?L,MNP 0.67pg/ ?L,MEHP 1.26 pg/ ?L,MOP 0.98 pg/ ?L,and control group MMP 2.41 pg/ ?L,MEP 2.74pg/ ?L,MBP 20.04 pg/ ?L,MBzP 0.11 pg/ ?L,respectively MNP 0.37 pg/ ?L,MEHP 0.23 pg/?L,MOP 0.38 pg/ ?L.Wilconxon paired rank test results showed that the content of MMP,MEP and MBP in PAES metabolites was not significantly different between the case group and the control group(P>0.05),and the difference in MBzP,MEHP,MOP,and MNP levels was statistically significant.Significance(P<0.05),and the case group content was higher than the control group.After corrected by Logisitic regression model,the risk of high BMI population(OR=3.16,P<0.05)was 3.16 times that of the general population;the risk of urinary highMEHP content(OR=3.08,P<0.05)was common to the general population;urinary high MBzP content population(OR=1.58,P<0.05)NAFLD was 1.58 times that of the general population.Conclusion:1.The detection rate of NAFLD among employees of the Group was as high as 31.7%.Compared with non-NAFLD populations,the age group,non-alcoholic fatty liver patients,BMI index,prevalence of diabetes in previous medical history,and serum TG and high and low density LDL are the main influencing factors.2.The effective separation and high accurate quantitative detection of many metabolites showed that the occupational population in our province was generally exposed to PAEs pollutants.3.The corrected results from the Logisitic regression model suggest that the exposure of the body to PAEs plasticizers is likely to trigger abnormal lipid metabolism and induce lipid metabolism disorders.