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標題: | 六輕工業區北鄰之彰化縣大城鄉居民尿中硫代二乙酸與非侵襲性肝纖維指標的關係 Association between Urinary Thiodiglycolic Acid and Non-invasive Liver Index in Residents of Dacheng Township north of No.6 naphtha cracking Complex |
作者: | Jun-Lin Chen 陳俊霖 |
指導教授: | 詹長權(Chang-Chuan Chan) |
關鍵字: | 氯乙烯單體,1,2 二氯乙烷,硫代二乙酸,尿液生物偵測,肝臟非侵襲性指標,成人, VCM,EDC,Urine biomonitoring,Non-invasive liver index,Adult, |
出版年 : | 2018 |
學位: | 碩士 |
摘要: | 背景
雲林縣麥寮鄉第六套輕油裂解廠工業區(六輕工業區)其中的製程使用1,2二氯乙烷(Ethylene dichloride, EDC)作為原料生產氯乙烯單體(vinyl chloride monomer, VCM)進而加工生產聚氯乙烯(polyvinyl chloride, PVC),這些製程會排放或是逸散VCM與EDC到空氣中。International Agency for Research on Cancer (IARC)將VCM分類為1類的人類致癌物質,將EDC分類為2B類可能致癌物質,VCM與EDC兩者都具有肝毒性會造成肝臟損傷、肝臟纖維化甚至肝硬化,人體暴露這兩個化學物質後會透過肝臟的P450酵素主要代謝成為硫代二乙酸(thiodiglycolic acid, TdGA)再經由尿液排出體外。 目的 透過尿液中的代謝物TdGA濃度分析推測居民暴露VCM、EDC的程度再以個案的血液分析資料計算非侵襲性肝纖維指標,Fibrosis-4 (FIB-4)。探討尿液TdGA濃度、研究個案住家和六輕工業區的距離與非侵襲性肝纖維指標之間的關係。 方法 研究個案為彰化縣大城鄉與竹塘鄉之成人居民,收案日期2016年4月10日與4月16日,收案內容包含尿液、血液樣本以及生活習慣問卷調查,將個案中分析結果未能符合實驗分析QA/QC、有服用維他命B群者、患有B、C肝炎者、血小板異常偏低者排除,並限制兩地區年齡分布區間(70歲以下)後個案共447位。TdGA的尿液樣本分析使用LC-MS/MS並用肌酐酸(creatinine)校正尿液濃度,並以四分位距分組,作為VCM、EDC的暴露指標,血液樣本生化檢查項目中以天冬氨酸氨基轉移酶(aspartate aminotransferase, AST)、丙氨酸轉氨酶(alanine aminotransferase, ALT)與血小板數量(Platelet count)當作非侵襲肝纖維指數的計算因子來評估研究個案肝損傷的程度,以多重羅吉斯迴歸分析探討TdGA與FIB-4之間的關聯性。 結果 TdGA與個案距離六輕工業區VCM/PVC廠的相關係數為-0.20,P值<0.05,距離六輕工業區較近的彰化縣大城鄉研究個案平均TdGA濃度為269.6 μg/g creatinine,距離六輕工業區較近的竹塘鄉研究個案平均TdGA濃度為199.25 μg/g creatinine。以FIB-4數值1.29當切分點預測個案肝纖維化,大城鄉個案FIB-4值大於1.29的個案比例為39%,竹塘鄉則為32%。在TdGA與FIB-4的多重羅吉斯迴歸分析中,校正性別、是否有在六輕工業區工作、抽菸習慣、飲酒習慣、BMI以及總膽固醇後發現TdGA變項中最高濃度的組別OR值為2.092 ( 95%CI: [1.171-3.774])並達到統計上的顯著。 結論 本研究發現個案住家距離六輕工業區VCM/PVC廠的距離越近,其尿液中TdGA濃度越高,個案中尿液TdGA濃度最高組別較濃度最低組別有2.092倍的風險其FIB-4>1.29,預測為具顯著肝纖維化者。本研究的結論認為六輕石化工業區的VCM/PVC工廠逸散或排放的VCM與EDC可能對南彰化地區的居民造成肝臟健康上的影響,使該地區居民肝纖維化的風險上升。 Background No.6 Naphtha Cracking Complex, one of the industrial processes, produces vinyl chloride monomer (VCM) and polyvinyl chloride (PVC) by Ethylene dichloride (EDC), which might release trace level of VCM and EDC in the atmosphere. International Agency for Research on Cancer (IARC) classified VCM, EDC as group 1, 2B respectively. Both VCM and EDC can also cause liver damage and lead to liver fibrosis even cirrhosis. Upon exposure, these will be metabolized by the cytochrome P450 enzymes and be excreted through urine as thiodiglycolic acid (TdGA). Aim Our objective is to estimate the VCM and EDC exposure level with urinary thiodiglycolic acid (TdGA) as biomarker and utilize non-invasive index (FIB-4) to evaluate the liver damages caused by VCM and EDC among residents in Southern Changhua County, then establish the correlation between TdGA and FIB-4. Methods Urine samples, blood samples and life style questionnaire were collected during 2016 April 10 and Apri 16 in Dacheng Township and Zhutang Township, South Changhua, Taiwan. The TdGA level in urine samples were analyzed by LC-MS/MS with the adjustment of creatinine, also divided into 4 groups dummy variables by IQR. Bases on the study population age distribution, subjects older than 70 years old were excluded. Subjects who take Vitamin B complex, have hepatitis B virus infection, hepatitis C virus infection and abnormal platelet counts were also excluded, then there are total 447 subjects. Non-invasive, Fibrosis-4 (FIB-4) were utilized to evaluate the liver fibrosis level caused by VCM and EDC. The Logistic regression model were developed to assess the relationship between urinary TdGA and FIB-4. Results The correlation betweenTdGA and the distances to industry of subjects is -0.20, and p-value <0.05. Subjects in Dacheng Township, is nearer to complex than Zhutang Townhip, average TdGA level is 269.6 μg/g creatinine, Subjects in Zhutang Township average TdGA level is 199.25 μg/g creatinine. With FIB-4 cuttof 1.29, subjects whos FIB-4 value over 1.29 were predicted to have significant liver fibrosis. Proportion of FIB-4 >1.29, in Dacheng Township is 39%, in Zhutang Township is 32%. In the logistic regression model , after adjusting gender, wrok in complex or not, smoke habbit, drink habbit, BMI and total cholesterol variables, we found that the highest TdGA concentration group (>Q3), OR is 2.092( 95%CI: [1.171-3.774]), p-value <0.05. Conclusion Subjects living near to VCM/PVC factory with increasing level of urinary TdGA. Subjects with the highest TdGA concentration (>Q3) has 2.092 times than subjects with the lowest TdGA concentration group (<Q1) to be led to FIB-4 >1.29. VCM/PVC factory of No.6 Naphtha Cracking Complex has probably affects residents living in South Changhua County, and increase the risk of liver fibrosis. |
URI: | http://tdr.lib.ntu.edu.tw/handle/123456789/1194 |
DOI: | 10.6342/NTU201801387 |
全文授權: | 同意授權(全球公開) |
顯示於系所單位: | 職業醫學與工業衛生研究所 |
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