Azathioprine hepatotoxicity, direct complication or secondary effect in rat liver transplantation.

The risk of azathioprine-induced hepatocellular damage was investigated using the auxiliary liver transplantation model in rats. This model permits to study the effect of the drug on both graft and the recipient's liver vascularized in different ways. Neither histopathological changes were observed, nor could any deaths be directly attributed to toxic effects of the drug on hepatocytes. Morphological lesions were absent in treated and untreated, subtotally hepatectomized rats with normal bile flow. However, lesions did become manifest after reimplantation (grafts) and/or ligation of the common bile duct (hosts). We concluded that in rats azathioprine is toxic for hepatocytes only when the normal bile flow is impeded, independent of the way of the liver vascularization.