Serum Cytokeratin 18 and Cytokine Elevations Suggest a High Prevalence of Occupational Liver Disease in Elastomer/Polymer Workers Highly Exposed to Acrylonitrile, Butadiene and Styrene

Abstract

Objective: Occupational liver disease is likely to be under-recognized because, in many cases, routine serologic liver chemistries are not effective biomarkers. Cytokeratin 18 (CK18) is a novel serologic biomarker for occupational liver disease. We recently demonstrated that serum CK18 and pro-inflammatory cytokines were elevated in chemical workers with toxicant-associated steatohepatitis (TASH) due to high-level vinyl chloride exposures. The purpose of this study is to determine the prevalence of CK18 elevation in elastomer/polymer workers exposed to mixtures of acrylonitrile, 1,3 butadiene, and styrene. Methods: 82 chemical workers were evaluated. CK18 was determined by ELISA and pro-inflammatory cytokines were measured by multianalyte chemiluminescent detection. Results: Mean routine liver chemistries (aspartate aminotransferase, alanine aminotransferase, total bilirubin, albumin, and alkaline phosphatase) were in the normal range. In fact, only 3 of 82 total subjects had any single lab abnormality detected by these tests. However, 39% (32 of 82) had elevated CK18 levels which were not explained by alcohol or obesity, except in potentially 4 cases. The pattern of CK18 elevation was consistent with TASH in the majority of cases (78%). TNFα, IL-6, IL-8, MCP-1, and PAI-1 were increased in these workers compared to those with normal CK18 levels. Conclusions: These results suggest a high prevalence of occupational liver disease and TASH in elastomer/polymer workers with elevated pro-inflammatory cytokines. Funding Information: NIEHS (P30ES014443-01A1, T35ES014559), the NIAAA (K23AA18399-01A, 1P01AA017103-01), and NCRR (5P20RR024489-02).