The role of the liver in exocrine pancreatic disease.

Heightened, but unmitigated, free radical activity within the liver, and the intrinsic bioactivity of certain FROPs and drug metabolites, would rationalise those liver aberrations that cannot be explained on the basis of enzyme induction. Thus the increased amounts of copper in bile suggest heightened production of non-biological reactive intermediates--perhaps derived from halogenated hydrocarbons [29]--and the consequent utilisation of glutathione; because it is known that copper in bile is bound to this protein. The increased amount of bilirubin in our patients' bile (Fig. 3), especially after an exacerbation of CP (Fig. 6), is reminiscent of the inductive response in rats that are deficient in certain antioxidants. Increased biliary concentration of bilirubin should predispose to pigment calculi. The liver biopsy changes of microvesicular fat and excess lipofuscin are in keeping with this general theme. The high concentrations of FROPs in our patients' bile, when viewed alongside evidence that certain products can alter the structure of gamma globulin and thereby its immunogenicity, may rationalise the cholangiographic and portal tract abnormalities--which fall into the sclerosing cholangitis/primary biliary cirrhosis spectrum--in our patients.