Hepatic injury associated with paraquat toxicity in humans

Thirteen patients are reported who developed evidence of hepatic damage after exposure to paraquat and subsequently died. At autopsy, the main changes involved the bile excretory pathways. Ten of the thirteen cases had cholestasis, usually localized to the centrilobular zone. There was cholangiocellular injury involving the small and medium-sized bile ducts in portal areas. It consisted of shrinkage of cells, poor definition of outline, separation from the basement membrane, desquamation of cells into the lumen, infiltration of the wall by neutrophils and possible loss of integrity of the basement membrane. These bile duct lesions have not been previously described in association with paraquat toxicity. On the basis of the overall histologic findings in this study and extrapolation from experimental studies, it is hypothesized that paraquat injury to the liver is biphasic; it is initially hepatocellular but becomes cholangiocellular after the first 2 days.