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Serum Cytokeratin 18 and Cytokine Elevations Suggest A High Prevalence of Occupational Liver Disease in Highly Exposed Elastomer/Polymer Workers

Cave, Matt MD; Falkner, Keith Cameron PhD; Henry, Latasha BS; Costello, Brittany BS; Gregory, Bonnie BS; McClain, Craig J. MD

Journal of Occupational and Environmental Medicine: October 2011 - Volume 53 - Issue 10 - p 1128–1133
doi: 10.1097/JOM.0b013e31822cfd68
Original Articles

Objective: Cytokeratin 18 (CK18) is a novel serologic biomarker for occupational liver disease. The purpose of this study is to determine the prevalence of CK18 elevation in elastomer/polymer workers exposed to acrylonitrile, 1,3-butadiene, and styrene.

Methods: A total of 82 chemical workers were evaluated. Cytokeratin 18 was determined by enzyme-linked immunosorbent assay and proinflammatory cytokines were measured by multi-analyte chemiluminescent detection.

Results: Thirty-nine percent (32 of 82) had elevated CK18 levels, which were not explained by alcohol or obesity, except in potentially four cases. The pattern of CK18 elevation was consistent with toxicant-associated steatohepatitis (TASH) in the majority of cases (78%). Tumor necrosis factor α, interleukin-6, interleukin-8, monocyte chemotactic protein-1, and plasminogen activator inhibitor-1 were increased in these workers compared with those with normal CK18 levels.

Conclusions: These results suggest a high prevalence of occupational liver disease and TASH in elastomer/polymer workers with elevated proinflammatory cytokines.

From the Department of Medicine Division of Gastroenterology, Hepatology, and Nutrition (Drs Cave, Falkner and McClain, Ms Henry, Ms Costello, and Ms Gregory) and Department of Pharmacology and Toxicology (Drs Cave and McClain), University of Louisville, and The Robley Rex Veterans Affairs Medical Center (Drs Cave and McClain), Louisville, Ky.

Address correspondence to: Matt Cave, MD, Department of Medicine Division of Gastroenterology, Hepatology, and Nutrition, University of Louisville, 505 S Hancock St, Louisville, KY 40202 (

This research was supported in part by the National Institute of Environmental Health Sciences (P30ES014443-01A1, T35ES014559), the National Institute on Alcohol Abuse and Alcoholism (K23AA18399-01A, 1P01AA017103-01), the National Center for Research Resources (5P20RR024489-02), the Department of Veterans Affairs, the Commonwealth of Kentucky (The University of Louisville Clinical & Translational Science Pilot Grant Program Advanced Award), and the National Institutes of Health Loan Repayment Program.

©2011The American College of Occupational and Environmental Medicine