The purpose of this investigation was to determine the efficacy of clinically available tests of hepatic function in detecting early hepatic changes associated with mixed solvent exposures. A cross-sectional investigation of 102 workers with a range of cumulative career exposure to organic solvents was conducted, ranging from carpenters with low cumulative exposure, millwrights with intermediate exposure, and industrial painters with higher cumulative exposure to mixed organic solvents. Data collection included an interview-administered questionnaire used to determine a cumulative exposure index to mixed general solvents, with both venous sample collection and hepatic ultrasonography performed at a regional medical center (Richland, WA). Laboratory evaluation of blood samples included tests of hepatic function parameters (ALT, AST, AP, GGT, and bilirubin), serum bile acid levels, and cytokine (pro-collagen biomarkers of hepatic fibrosis) analyses. In addition to comparison of hepatic biomarkers by job classification (carpenter, millwright, painter), multiple linear regression analyses were performed to assess hepatic biomarker levels as a function of a cumulative exposure (by a semi-quantitative exposure index), adjusting for confounders of age, gender, alcohol intake, body mass index, and serologic evidence of prior Hepatitis B/c infection. A significant increase in the hepatic cholestatic enzyme gamma glutamyl transpeptidase (GGT) was observed in painters, with a mean level of 41 IU/L , compared with carpenters and millwrights (27 IU/L; p equal to or less than 0.05). This effect was also demonstrated by a significant exposure-response for GGT and cumulative career exposure to mixed general solvents, observed in multiple linear regression analyses controlling for age, gender, alcohol, body mass index (p equal to or less than 0.05). In association with this cholestatic biochemical change, a trend towards moderate to severe sonographic parenchymal changes in association with general solvent exposure was observed by ultrasound (p=0.07). Other tests for hepatic biochemical function including hepatic transaminases (ALT, AST) and serum bile acids demonstrated no consistent exposure-response relationship with mixed solvents. Among the pro-collagen biomarkers of fibrosis, a trend towards elevation of Procollagen III was observed in millwrights (p=0.07). The significant exposure-response relationship between career cumulative exposure to mixed solvents and hepatic GGT levels supports a primary cholestatic effect of solvents, with an associated trend for hepatic parenchymal changes on ultrasonography. The absence of consistent elevations in cytokine biomarkers of fibrosis suggests that these ultrasonographic findings represent steatosis rather than fibrosis. The cholestatic hepatic effects observed in this study appear to be most prominent in industrial painters, a group with high exposure to mixed solvents.
University of Washington, Occupational and Environmental Medicine Program, Harborview Medical Center, Box 359739, 325 Ninth Avenue, Seattle, WA 98104
University of Washington, Occupational and Environmental Medicine Program, Harborview Medical Center, Seattle, WA 98104