Abstract
BACKGROUND: Biliary obstruction impairs liver function although the pathophysiological mechanism is incompletely understood. AIMS: The aim of this study was to examine serial changes in liver metabolism in patients with obstructive jaundice using image guided in vivo 31-phosphorus magnetic resonance spectroscopy ((31)P MRS). This technique allows repeated and non-invasive assay of organ energy metabolism and phospholipid biochemistry. PATIENTS: We studied 10 patients presenting with obstructive jaundice secondary to extrahepatic localised malignancy. There were eight men and two women, median age 72 years (range 54-94), six with cholangiocarcinoma (all Bismuth type 1) and four with carcinoma of the head of the pancreas. Ten healthy volunteers (median age 24 years (range 21-26)) were studied for comparison. METHODS: Hepatic metabolism in jaundiced patients was measured by (31)P MRS at presentation and again after a one week period of biliary drainage. Conventional liver function tests were also recorded. RESULTS: Compared with controls, liver spectra from jaundiced patients contained an excess of phosphomonoester (PME) metabolites (PME/total phosphate median 10.3% (interquartile range 8.7-11.5) in controls, 15.4% (13.1-17.7) in jaundiced cases; p<0.01). Biliary decompression was achieved in all patients (five with internal stents and five by external drainage catheters), and plasma biochemistry improved predictably (bilirubin 176 micromol/l (158-351) at presentation, 110 micromol/l (42-241) after drainage for one week; p<0.01). Enhancement of hepatic energy status, measured by the ratio of adenosine triphosphate (ATP) to inorganic phosphate (Pi), was observed in all cases after relief of biliary obstruction (ATP/Pi 1.4 (1.17-1.69) at presentation, 1.97 (1.4-2.48) after drainage; p<0.01) and was independent of the route of bile drainage. Hepatic phosphodiester (PDE) content was decreased after relief of obstruction (PDE/total phosphate 25.2% (20.5-27.4) at presentation, 19.8% (16.6-24.5) after drainage; p<0.01). This change was probably due to a reduction in the contribution from bile contents to this resonance as a strong PDE signal was also detectable in spectra obtained from separate bile specimens. CONCLUSIONS: Obstructive jaundice produces alterations in liver phosphoester biochemistry, most likely reflecting disturbances in phospholipid metabolism. Relief of biliary obstruction is associated with a measurable increase in hepatic energy status. Bile may contribute to the phosphodiester signal of the 31-phosphorus liver spectrum and changes in these resonances must therefore be interpreted with caution and in relation to the clinical situation. Monitoring of liver metabolism by (31)P MRS may allow clinicians to refine the selection and timing of therapeutic options in jaundiced patients.