A 2-YEAR PROSPECTIVE-STUDY OF THE EFFECT OF URSODEOXYCHOLIC ACID ON URINARY BILE-ACID EXCRETION AND LIVER MORPHOLOGY IN CYSTIC FIBROSIS-ASSOCIATED LIVER-DISEASE

The efficacy of 2 years of treatment with ursodeoxycholic acid (UDCA) in cystic fibrosis (CF)-associated liver disease was evaluated by live r biopsies and liver function tests in 10 patients aged 8 to 28 years. The metabolism of UDCA was investigated by analysis of urinary bile a cids with fast atom bombardment mass spectrometry (FABMS) and gas-liqu id chromatography-mass spectrometry. Eight patients responded with nor malization of liver function tests (LFT) and all with decreased serum levels of immunoglobulin G (IgG). Blind evaluation of liver biopsies i ndicated improved liver morphology with less inflammation and/or bile duct proliferation than before treatment with UDCA in 7 patients. Only 1 patient had signs of progression of clinical liver disease. The pro portion of UDCA and isoUDCA in urine varied, but increased during trea tment from a mean (median) of approximately 4% (3%) to 40% (40%) of to tal bile acids, The increase was not related to LFT. The secondary bil e acids, such as lithocholic acid (LCA) and deoxycholic acid (DCA), di d not increase significantly. The excretion pattern of glycosidic conj ugates of UDCA and its metabolites was similar to that found in health y individuals, UDCA and isoUDCA being mainly excreted in conjugation w ith N-acetylglucosamine. This study shows that UDCA modulates inflamma tion in CF-associated liver disease and indicates improvement of liver morphology during 2 years of treatment.