Do occupational exposures to vinyl chloride cause hepatocellular carcinoma and cirrhosis?

Abstract

Controversy exists about the association between occupational exposures to vinyl chloride and hepatocellular carcinoma and cirrhosis. Two large multicentre mortality cohort studies, one American and another European, reported higher mortality for primary cancer of liver and biliary tract. However, the American study was not able to rule out misclassification, because based on death certificates and under the heading primary liver cancers, some angiosarcomas, the typical neoplasia associated with vinyl chloride, may have been included. The American study does not report on cirrhosis mortality. The European study also reports higher mortality of primary liver cancer, but contrary to the American study in a further analysis based on 10 verified cases of hepatocellular carcinoma, an exposure‐response trend with duration of employment and with cumulative exposure to vinyl chloride was detected. A smaller cohort belonging to this multicentre cohort confirmed these results. Meta‐analyses based on the two large cohorts concluded for a small excess of primary liver cancer, although misclassification could not be ruled out. Excess risk of cirrhosis was reported in the European cohort, in a subcohort and in a cross‐sectional study. However, a meta‐analysis did not confirm this excess. Several critical appraisals of the literature reached antithetical conclusions about hepatocellular carcinoma, cirrhosis and occupational exposures to vinyl chloride. For both hepatocellular carcinoma and cirrhosis, a study suggests an additive and multiplicative effect of vinyl chloride exposure with viral hepatitis and alcohol consumption respectively. Pathology reports seem to indicate a possible development of hepatocellular carcinoma but not of cirrhosis after high exposures to vinyl chloride.

EASL Clinical Practice Guideline: Occupational liver diseases

“…The pooled relative risk (RR) was 0.73 (95% CI 0.61-0.83), with no evidence of heterogeneity or publication bias. Thus, the available epidemiological data do not support a relationship between occupational exposure to VCM and cirrhosis, 15 which is in agreement with experimental studies of VCM-exposed rodents and pathology reports of VCM-exposed workers and patients with VCM-related liver angiosarcoma. These studies did not observe evidence of cirrhosis, only periportal fibrosis.…”

“…26,27 It is therefore unclear if the excess risk was real or due to misclassification of HCC. 12,15 In any case, in 2012, the IARC confirmed its earlier conclusion on VCM exposure as a causal factor for HCC. 24,25 In 2017, a US collaborative re-analysis provided results updated up to 2013 and, based on 32 deaths from the disease, found that the increased risk of HCC was restricted to workers with very high estimated cumulative exposures, i.e.…”

EASL clinical practice guidelines for the management of occupational liver diseases

“…The higher prevalence rates of self‐reported unspecified ‘liver diseases’ observed in blue‐collar or unskilled workers, often associated with tobacco and alcohol use, makes it difficult to determine causation . This was the case in European workers with high level exposure to vinyl chloride monomer (VCM), resulting in 203 deaths from cirrhosis . .…”

Endocrine Disruptors and Carcinogenesis

“…Pathology reports seem to indicate a possible development of hepatocellular carcinoma but not of cirrhosis after high exposures to vinyl chloride [63]. Further, Guardiola demonstrated that occupational exposure to polyvinyl chloride generated a distinct plasma metabolome with markedly altered lipid and amino acid metabolites [64].…”