Toxicant-associated steatohepatitis in vinyl chloride workers.
Toxicant-associated steatohepatitis in vinyl chloride workers.
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DOI：
10.1002/hep.23321
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发表时间：
2010-02
期刊：
影响因子：
13.5
通讯作者：
McClain, Craig J.
中科院分区：
文献类型：
--
作者：
Cave, Matt;Falkner, Keith Cameron;Ray, Mukunda;Joshi-Barve, Swati;Brock, Guy;Khan, Rehan;Homme, Marjorie Bon;McClain, Craig J.
虽然非酒精性脂肪性肝炎（NASH）通常与肥胖有关，但据报道，它也发生在暴露于工业化学品的瘦个体中。氯乙烯（VC）的职业暴露是血管肉瘤的一个有据可查的危险因素，但以前没有与脂肪性肝炎相关。在这里，我们评估了25名非肥胖，高暴露，VC工人的脂肪性肝炎肝活检。接下来，我们评估了相关的代谢和细胞因子异常受影响的工人控制的26个化学工人，没有到最低限度的VC暴露，和11个未暴露的健康志愿者。在高暴露VC工人中，脂肪性肝炎的患病率为80%。其中，55%患有纤维化，4例患有血管肉瘤。我们创造了一个术语，毒物相关性脂肪性肝炎（TASH），来描述这种不能用肥胖或酒精解释的疾病。虽然平均血清转氨酶是正常的TASH，总细胞角蛋白18，但不是半胱天冬酶裂解片段，升高。尽管没有肥胖，但患有TASH的工人有胰岛素抵抗，脂联素水平降低。TASH还与血清肿瘤坏死因子α和白细胞介素1β、6和8显著升高相关。血清抗氧化活性降低TASH。TASH经常发生在这些非肥胖VC工人与高累积暴露和正常的肝酶。总细胞角蛋白18升高提示TASH中存在坏死性细胞死亡，可能是一种有用的血清学生物标志物。TASH的进一步特征是胰岛素抵抗、促炎细胞因子升高和抗氧化防御受损。阈值VC暴露和其他化学试剂在TASH中的作用尚不清楚。
Although nonalcoholic steatohepatitis (NASH) is typically associated with obesity, it has also been reported to occur in lean individuals exposed to industrial chemicals. Occupational exposure to vinyl chloride (VC) is a well-documented risk factor for hemangiosarcoma, but has not previously been associated with steatohepatitis. Here, we evaluate liver biopsies from 25 non-obese, highly-exposed, VC workers for steatohepatitis. Next, we evaluate associated metabolic and cytokine abnormalities in affected workers controlled by 26 chemical workers with no to minimal VC exposures, and 11 unexposed, healthy volunteers. Among highly-exposed VC workers, the prevalence of steatohepatitis was 80%. Of these, 55% had fibrosis and four had hemangiosarcoma. We have coined the term, toxicant-associated steatohepatitis (TASH), to describe this condition which was not explained by obesity or alcohol. Although mean serum transaminases were normal in TASH, total cytokeratin18, but not the caspase-cleaved fragment, was elevated. Despite the absence of obesity, workers with TASH had insulin resistance with reduced adiponectin levels. TASH was also associated with markedly elevated serum tumor necrosis factor alpha and interleukins 1β, 6, and 8. Serum antioxidant activity was reduced in TASH. TASH occurred frequently in these non-obese VC workers with high cumulative exposures and normal liver enzymes. Elevated total cytokeratin 18 suggested the presence of necrotic cell death in TASH and may be a useful serologic biomarker. TASH was further characterized by insulin resistance, elevated pro-inflammatory cytokines, and impaired antioxidant defenses. The threshold VC exposure and the role of other chemical agents in TASH are as yet unknown.
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DOI：
10.1097/01.jom.0000137722.66767.38
发表时间：
2004-09-01
影响因子：
3.2
作者：
Hsiao, TJ;Wang, JD;Cheng, TJ
通讯作者：
Cheng, TJ
影响因子：
5.9
作者：
DANNAHER, CL;TAMBURRO, CH;YAM, LT
通讯作者：
YAM, LT
DOI：
10.1111/j.1478-3231.1999.tb00053.x
发表时间：
1999-08-01
期刊：
LIVER
影响因子：
--
作者：
Cotrim, HP;Andrade, ZA;Freitas, LAR
通讯作者：
Freitas, LAR
影响因子：
4.5
作者：
Hsieh, Hui-I;Chen, Pau-Chung;Cheng, Tsun-Jen
通讯作者：
Cheng, Tsun-Jen
影响因子：
6.7
作者：
Cotrim, HP;De Freitas, LA;Andrade, Z
通讯作者：
Andrade, Z