Mortality from liver angiosarcoma, hepatocellular carcinoma, and cirrhosis among vinyl chloride workers

Fedeli, Ugo; Girardi, Paolo; Gardiman, Giulio; Zara, Davide; Scoizzato, Luca; Ballarin, Maria Nicoletta; Baccini, Michela; Pirastu, Roberta; Comba, Pietro; Mastrangelo, Giuseppe

doi:10.1002/ajim.22922

Cited by 22 publications

(23 citation statements)

References 18 publications

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“…Moreover, this model has been, and can be further, used to investigate intervention therapies and indepth mechanistic studies of the mode of action for this prevalent toxicant 24 . As VC is a known carcinogen 26,27,28 , this exposure paradigm can also be modified for the study of VC-induced cancer. Other co-morbidities like alcoholic liver disease may also be enhanced by VC co-exposure.…”

Section: Representative Resultsmentioning

confidence: 99%

Vinyl Chloride and High-Fat Diet as a Model of Environment and Obesity Interaction

Lang

Goldsmith

Schnegelberger

et al. 2020

JoVE

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Vinyl chloride (VC), an abundant environmental contaminant, causes steatohepatitis at high levels, but is considered safe at lower levels.Although several studies have investigated the role of VC as a direct hepatotoxicant, the concept that VC modifies sensitivity of the liver to other factors, such as nonalcoholic fatty liver disease (NAFLD) caused by high-fat diet (HFD) is novel. This protocol describes an exposure paradigm to evaluate the effects of chronic, low-level exposure to VC. Mice are acclimated to low-fat or high-fat diet one week prior to the beginning of the inhalation exposure and remain on these diets throughout the experiment. Mice are exposed to VC (sub-OSHA level: <1 ppm) or room air in inhalation chambers for 6 hours/day, 5 days/week, for up to 12 weeks. Animals are monitored weekly for body weight gain and food consumption. This model of VC exposure causes no overt liver injury with VC inhalation alone. However, the combination of VC and HFD significantly enhances liver disease. A technical advantage of this co-exposure model is the whole-body exposure, without restraint. Moreover, the conditions more closely resemble a very common human situation of a combined exposure to VC with underlying nonalcoholic fatty liver disease and therefore support the novel hypothesis that VC is an environmental risk factor for the development of liver damage as a complication of obesity (i.e., NAFLD). This work challenges the paradigm that the current exposure limits of VC (occupational and environmental) are safe. The use of this model can shed new light and concern on the risks of VC exposure. This model of toxicant-induced liver injury can be used for other volatile organic compounds and to study other interactions that may impact the liver and other organ systems.

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Section: Representative Resultsmentioning

confidence: 99%

Vinyl Chloride and High-Fat Diet as a Model of Environment and Obesity Interaction

Lang

Goldsmith

Schnegelberger

et al. 2020

JoVE

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“…However, such mis-classification did not probably affect the main results since findings were confirmed after exposures were lagged by 10-40 years. More recently, an update of an Italian cohort of vinyl chloride workers found a strong association with VCM cumulative exposure in a large series of HCC confirmed by histology and/or clinical records[11]. In summary, all the original studies available provide compelling evidence of the causal role of occupational VCM exposure in the development of HCC (Table 1).…”

Section: Hepatocellular Carcinomamentioning

confidence: 98%

“…In the European cohort of vinyl chloride workers, an increase in liver cancer risk (all types) with increasing exposure was confirmed in analyses restricted to subjects with cumulative exposure < 1500 ppm-years[3]. In an Italian cohort, an approach based on a non-parametric regression was adopted to model in continuous form the relationship between exposure and mortality considering 31 confirmed HCC cases; HCC mortality rates were found to increase with cumulative VCM exposure already in the range below 2000 ppm-years[11]. In view of the above data, the risk of HCC seems not to be confined only to a few subjects in the highest exposure categories, but probably involves most workers from the United States and Europe, who had relevant exposures to VCM before the major improvements in working conditions achieved in the mid-1970s.…”

Section: Hepatocellular Carcinomamentioning

confidence: 99%

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Occupational exposure to vinyl chloride and liver diseases

Fedeli¹,

Girardi²,

Mastrangelo³

2019

WJG

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Portal hypertension, liver fibrosis, and angiosarcoma of the liver (ASL) have been reported among workers exposed to vinyl chloride monomer (VCM) since the 1970s. In 2007, the International Agency for Research on Cancer established the association of VCM with hepatocellular carcinoma (HCC), though only on the basis of the few cases available. Thereafter, recent reports from the United States cohort and a European sub-cohort of vinyl chloride workers provided compelling evidence of a strong association between cumulative VCM exposure and HCC risk. Further areas of research include the risk of liver cancer at lower levels of exposure and different patterns of risk of ASL and HCC with the time since exposure. The evidence of interaction between VCM exposure and other known liver carcinogens such as alcohol and chronic viral infection provides clues for the health surveillance of exposed workers. Notably, also the risk of VCM-associated chronic liver disease is modulated by alcohol consumption, viral infection, and genetic polymorphism. A counter-intuitive finding from cohort studies of exposed workers is the lower mortality from liver cirrhosis with respect to the general population; this can be attributed to the healthy worker effect and to the selection of liver cancer as the cause of death in the presence of concomitant chronic liver disease. Studies designed to overcome these intricacies confirmed an association between cumulative VCM exposure and the risk of liver cirrhosis.

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“…While periportal fibrosis has been clearly associated with long-term exposure to VCM, progression to cirrhosis has been discussed much more. 116,117 An excess of deaths from nonalcohol related cirrhosis has been observed among female rubber workers, suggested to be associated with occupational exposure to nitrosamines. 118 Vascular disorders A number of vascular lesions may be produced by toxicants.…”

Section: Fibrosismentioning

confidence: 99%

EASL Clinical Practice Guideline: Occupational liver diseases

Colombo¹,

Vecchia²,

Lotti³

et al. 2019

Journal of Hepatology

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A variety of chemicals have been linked to occupational liver diseases, including several solvents and mixtures thereof, pesticides, and metals. Workplace exposures have been associated with virtually the entire spectrum of acute and chronic liver diseases. However, their prevalence is inadequately quantified and their epidemiology limited. Occupational liver diseases may result from high accidental or from prolonged lower level exposures. Whereas the former is uncommon and easily recognised, the latter are relatively more frequent but often overlooked because they may display normal values of conventional markers, have an insidious onset and be asymptomatic or be obfuscated and confounded by concurrent conditions. In addition, specific tests of toxicity are not available, histopathology may not be revealing and the assessment of internal dose of chemicals is usually not decisive. Given these circumstances, the diagnosis of these liver disorders is challenging, one of exclusion and often requires an interdisciplinary approach. These recommendations offer a classification of the type of liver injuries associated with occupational exposures-based in part on the criteria for drug-induced liver injury-a grading of their severity, and the diagnostic and preventive criteria for chemically induced occupational liver disease.

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Mortality from liver angiosarcoma, hepatocellular carcinoma, and cirrhosis among vinyl chloride workers

Cited by 22 publications

References 18 publications

Vinyl Chloride and High-Fat Diet as a Model of Environment and Obesity Interaction

Vinyl Chloride and High-Fat Diet as a Model of Environment and Obesity Interaction

Occupational exposure to vinyl chloride and liver diseases

EASL Clinical Practice Guideline: Occupational liver diseases

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