Copper metabolism and biliary secretion in patients receiving orthotopic liver transplantation

The quantitative aspects of biliary copper excretion in health and disease have not been fully defined yet. The aim of the study was to evaluate copper metabolism and biliary excretion of patients who have received an orthotopic liver transplant (OLT) during the immediate postoperative period.

We have studied retrospectively 16 patients undergoing primary OLT and eight undergoing cholecystectomy, and measured serum concentration of copper and its secretion in bile and urine by flame atomic absorption spectrometry (FAAS).

We found a progressive increase of biliary copper secretion rates and a corresponding lowering of urinary copper during the postoperative period. Thus, in OLT patients, the mean of biliary copper secretion on day 1 is 0.7+/-0.2 micromol/day compared with 2.3+/-1.1 micromol/day on day 7 (p<0.01) and 6.1+/-2.5 micromol/day on day 15 (p<0.0001). The rate of copper output on day 5 after surgery is about one sixth of the value reported for patients who had undergone cholecystectomy. In patients suffering an acute rejection episode, there was an abrupt fall in bile flow (<15 ml/day) and excretion of biliary copper (<1 micromol/day), accompanied by an increase of urine copper excretion (>3 micromol/day), and both were recovered when the rejection episode was solved. We found an inverse relationship between the serum bilirubin (Bt), alkaline phosphatase (ALP) and the biliary copper excretion (p<0.01), and a direct relationship with urinary copper excretion (p<0.01).

The copper measurements in urine and bile are non-invasive techniques, of low cost, rapid and easy to accomplish, and available in hospitals accredited for hepatic transplantation. These characteristics make these methods helpful in the monitoring of patients submitted to OLT for assessment of graft quality and subsequent outcome.