Iscopperhepatotoxic inprimary biliary cirrhosis

SUMMARY Inprimary biliary cirrhosis (PBC)liver copperretention occursas a complication of cholestasis. Byanalogy withWilson's disease, ithasbeensuggested that copperretention ishepatotoxic inPBC,andthis hasbeentherationale fortheuseofD-penicillamine inthis disease. The hypothesis that copperishepatotoxic inPBChasnotbeentested andinthis study we haveevaluated therole ofliver copperretention inthepathogenesis ofPBC. Sixty-four patients withPBChavebeenstudied. Fifty-four hadincreased liver copperconcentrations. Liver cell synthetic function was wellpreserved. Allthepatients hadnormalprothrombin times, andonly twohadsubnormal serumalbumin concentrations. There was no correlation between liver copperconcentrations andthedegree ofliver cell damageassessed biochemically (aspartate transaminase), andhistologically. Electron microscopy was performed on liver biopsies fromfive patients withmarkedly increased liver copperconcentrations. Theliver cell ultrastructure was compatible withcholestasis. Liver cells contained electron dense lysosomes, which were shownto contain copperandsulphur byx-rayprobemicroanalysis. Thecharacteristic organelle changes associated with coppertoxicity inWilson's disease werenotobserved. Thebiochemical, histological, andhistochemical differences between PBCcomplicated byliver copperretention, andWilson's disease, indicates that there aredifferences inthehandling ofcopper inthese disease. Inthis study we could find no evidence tosuggest that copperplays an important role inthepathogenesis ofliver dysfunction inPBC.