職場肝功能異常原因暨肝病管理探討

obesity, iron, chemical and liver diseases

蕭敦仁(Tun-Jen Hsiao)

指導教授 ： 王榮德

國立臺灣大學/公共衛生學院/職業醫學與工業衛生研究所/博士(2005年)

https://doi.org/10.6342/NTU.2005.01912

摘要

肝病是我國國民重大死因之一，每年死於肝病的國人超過10,000名，因此如何降低肝病死亡率是我們共同努力的目標；傳統上多以醫院及社區為肝病防治戰場，但是職場中多為青壯年人口，為社會的重要支柱，又擁有族群穩定的優勢，因此只要企業主願意配合，職場是一個非常適合進行肝病防治的場所。
肝病的種類繁多，但在台灣地區最重要的是病毒性肝炎、脂肪肝、酒精性肝病、藥物及化學性肝病、以及各種肝病較不好的結局---肝硬化及肝癌。其中以病毒性肝炎中的B型及C型肝炎荼毒國人健康最劇，80%的肝硬化病患及90%的肝癌病患與之相關；而脂肪肝則是台灣最盛行的肝病，其盛行率約21-25%，遠高於B型肝炎的15-20%及C型肝炎的2-4%；酒精性肝病雖然沒有全國性的流行病學調查，但臨床上此類病患越來越多；至於藥物及化學性肝病，其中前者多見於零星的個案報告，而後者則是職場必須特別注意的肝病。
本研究以兩種不同產業工廠為研究族群，探討職場中肝病之盛行狀況及其危險因子；並進一步分析工廠中最常見的肝病：脂肪肝的致病機轉及治療方式。最後並嘗試以研究中所瞭解之職場肝病危險因子進行肝病管理。
本研究共分四大部份，分別摘要如下：

第一部份：以PVC工廠為題材，共檢查全國五家PVC工廠347位員工，以肝臟超音波檢查為工具。其主要發現如下：
1. PVC從業員工肝纖維化之盛行率為5.8%。
2.肥胖症、病毒性肝炎、及氯乙烯累積暴露量過大是PVC員工肝臟纖維化之主要原因。

第二部份：脂肪肝為職場中最常見的肝病，但其其致病機轉並不全然瞭解，也欠缺有效治療方式，因此研究非酒精性脂肪肝之致病機轉，以做為治療之基礎。此部份共仔細評估210位BMI≧28之不喝酒的肥胖者，在進入減肥班之前以ALT及肝臟超音波體檢，其主要發現如下：
1. 脂肪肝只發現在80%肥胖者身上；而腰圍較粗及胰島素抗性增加為其危險因子。
2 肥胖者中合併脂肪肝之人，出現ALT異常升高者佔25.6%；而較高的鐵蛋白 (Ferritin)及較高的胰島素抗性為其危險因子。
第三部份：減肥是脂肪肝的有效治療模式，但其效果有待評估，本研究以53位BMI≧25之非酒精性脂肪肝病患者接受24週之減肥治療，其主要發現如下：
1. 24週平均體重下降為 8.6 ±5.0 kgs或原體重之10.3±5.6%。
2. ALT平均由 92.7 ±43.9 IU/L 降至31.6±16.2 IU/L，其中37位(70%) ALT恢復正常(p < 0.01)。
3. Fatty score (0-15分)則由平均由9.4 ±2.7降為3.6 ±2.7 (p <0.01)。
4. 新陳代謝症候群之盛行率由減肥前之41.5%降至減肥後之11.3%。
5. 以mixed linear model進行統計，發現在24週內，四週內體重每下降一公斤，ALT平均下降2.3 ±0.3 IU/L。

第四部份：以TFT-LCD作業員工為主，致力找出各種ALT上升的危險因子，並以此為職場肝病管理計劃之基礎。共有3,875位接受完整檢查，包括問卷調查、血液檢查、及肝臟超音波檢查，其主要發現如下：
1. ALT異常率為17.2%
2. ALT異常之顯著危險因子為：B型肝炎、C型肝炎、脂肪肝、較高的BMI、ferritin、 及insulin resistance，以及男性、較年輕、及工作於剝膜部。
3.剝膜部之主要暴露為monoethanolamine (MEA)及dimethyl sulfoxide (DMSO)。

關鍵字

肥胖 ； 鐵蛋白 ； 單乙醇氨 ； 肝功能 ； 脂肪肝

並列摘要

Liver diease is a major leading cause of mortality in Taiwan. The number of died in liver diseases more than 10 thousand per year in this island. So how to lower the mortality rate of iver disease is our common direction of effort. In tradition, hospital and community are the main sites of liver disease prevention. But in worksites, the more stable and young workers make it an important and suitable site for the program of liver disease prevention if the administrators agree.
There are many types of liver diseases, including viral hepatitis, non-alcoholic fatty liver disease, alcoholic liver disease, chemical and drug-induced liver injuries and their worse common outcomes- liver cirrhosis and hepatoma. Among the diversity of etiology of liver diseases, viral hepatitis has the worst health effect to victims; indeed, 80% of liver cirrhosis and 90% hepatoma related to the infection. Fatty liver is the most prevalent liver disease in Taiwan, the prevalence is about 21-25%, which is more than 15-20% of hepatitis B and 2-4% of hepatitis C. Although there is no national prevalence study of acoholic disease, the number of this kind of patients increased clinically. In that of drug-induced and chemical liver injury, the former only occur in occasional case reports, and the latter is the most important typr of liver disease which we should pay more attention to it in worksites.
This report consists of the studies of workers of two different plants to determine the prevalence and risk factors of liver diseases. We also further investigate the mechanism and the effect body weight reduction in treatmentof the most prevalent fatty liver.
This report is composed of 4 parts, the summaries are as below:

Part I. Liver fibrosis in asymptomatic poly-vinyl chloride workers
This study was designed to determine whether vinyl chloride monomer (VCM) exposure is associated with liver fibrosis. A total of 347 workers with occupational exposure to VCM were systemically examined using liver ultrasonography and routine liver function tests. Major findings were as below:
1. The prevalence of liver fibrosis in PVC workers was 5.8%.
2. Significantly increased risks of developing liver fibrosis were found in workers who had history of high exposure jobs, hepatitis B and/or C infection and body mass index greater than or equal to 25.

Part II. Insulin resistance and ferritin as major determinants of nonalcoholic fatty liver disease in apparently healthy obese patients
Two hundred and ten apparently healthy obese patients, aged from 18-65 years, with a body mass index (BMI) of 28 or more, were enrolled in a body weight reduction program in our hospital. All the subjects underwent screening and pre-program examinations including anthropometric data measurements, biochemistry testing, and ultrasonography of the liver. NAFLD was defined as fatty liver diagnosed by ultrasonograpgy plus persistent elevation of alanine aminotransferase (ALT) levels. The major findings were as below:
1. Fatty liver was found in only 80% (168/210) subjects with the risk factors of larger waist circumference and higher insulin resistacne.
2. Persistent ALT elevation was further detected in 25.6% (43/168) of subjects with the risk factors of higher serum ferritin level and insulin resistance.

Part III. Effects of body weight reduction in obese subjects with NAFLD
To assess the effect of body weight reduction in obese subjects with non-alcoholic fatty liver disease (NAFLD) and persistent elevated ALT. 54 patients were enrolled from our out patients department. These patients received 24 weeks of patial meal replacement with low calorie diet and exercise program. Fatty score from liver sonography were the sum score of liver-kidney contrast, masking of GB wall, blurring of portal vein, blurring of hepatic vein, and ultrasound far attenuation. 53 patietns completed the program.The major findings were as below:
1. The body weight reduction was 8.6 kgs on average, or 10.3% of initial body weight.
2. ALT was reduced from 92.7IU/L to 31.6 IU/L (p < 0.001). 37 (70%) out of the 53 patients had normal ALT value at the end of treatment.
3. The fatty scores of liver by ultrasound were reduced form 9.4 to 3.6 (p < 0.001).
4. The prevalence of metabolic syndrome was decreased from 41.5% to 11.3% after body weight reduction.
5. Linear mixed model analyses showed that within 24 weeks’ therapy, the average reduction of ALT was 2.3

Part IV. Elevated serum alanine transaminase level associated with stripping operation in thin film transistor workers: Is monoethanolamine the responsible agent?
The purpose of this study was to determine the etiology of elevated levels of alanine aminotransferase (ALT) among workers in Taiwan’s thin film transistor (TFT) industry.
3875 out of 4051 workers completed a structured questionnaire. Everyone received blood tests for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus antibody (Anti-HCV), ALT, insulin, and ferritin, and also underwent ultrasonographic examination of liver.
1. Six hundred sixty-seven (17.2%) employees were found to have elevated levels of ALT.
2. The risk factors of ALT elevation were: HBsAg, anti-HCV, fatty liver, higher BMI, ferritin, insulin resistance, being male, being younger, and working in stripping department .
3. The major exposure occurred during stripping operation were a solvent containing 70% of monoethanolamine (MEA) and 30% of dimethyl sulfoxide (DMSO).

並列關鍵字

obesity ； ferritin ； monoethanolamine ； liver function test ； fatty liver

參考文獻

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