Toxicant-associated steatohepatitis

Abstract

Hepatotoxicity is the most common organ injury due to occupational and environmental exposures to industrial chemicals. A wide range of liver pathologies ranging from necrosis to cancer have been observed following chemical exposures both in humans and in animal models. Toxicant-associated fatty liver disease (TAFLD) is a recently named form of liver injury pathologically similar to alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD). Toxicant-associated steatohepatitis (TASH) is a more severe form of TAFLD characterized by hepatic steatosis, inflammatory infiltrate, and in some cases, fibrosis. While subjects with TASH have exposures to industrial chemicals, such as vinyl chloride, they do not have traditional risk factors for fatty liver such as significant alcohol consumption or obesity. Conventional biomarkers of hepatotoxicity including serum alanine aminotransferase activity may be normal in TASH, making screening problematic. This article examines selected chemical exposures associated with TAFLD in human subjects or animal models and concisely reviews the closely related NAFLD and ALD.

Figure 1

Photomicrograph of a liver biopsy from an obese adult human subject with nonalcoholic steatohepatitis showing macrovesicular steatosis, inflammatory infiltrate, and hepatocyte ballooning with Mallory-Denk bodies (arrows, hematoxylin–eosin stain, 100×).

Figure 2

Liver photomicrograph from a C57/Bl6 mouse fed a Western diet for 12 weeks, demonstrating small and large dropletmacrovesicular steatosis and foci of inflammatory infiltrates (hematoxylin–eosin stain, 40×).

Figure 3

Liver photomicrograph from a C57/Bl6 mouse administered ethanol (28 g/kg/day) for 4 weeks, demonstrating macrovesicular steatosis and foci of inflammatory infiltrates (hematoxylin–eosin stain, 40×).

Figure 4

Computed tomography scan from a VC worker with a 20 cm hypodense liver mass which was subsequently confirmed to be hemangiosarcoma on biopsy. VC = vinyl chloride.

Figure 5

Photomicrograph of a liver biopsy (100×, hematoxylin–eosin [H&E] stain) of a VC worker with TASH and cirrhosis. VC = vinyl chloride; TASH = toxicant-associated steatohepatitis.