URINARY ASSAYS FOR DESMOSINE AND HYDROXYLYSYLPYRIDINOLINE IN THE DETECTION OF CIRRHOSIS

Background/Aims: Non-invasive markers of liver fibrosis have great pot ential for both the diagnosis and therapy of liver disease and cirrhos is, The aim of this study was to evaluate the potential of urinary ami no acids desmosine (DES) and isodesmosine (IDES) derived from the brea kdown of elastin and hydroxylysylpyridinoline (HP) and lysylpyridinoli ne (LP) derived from fibrillar collagen in diagnosing chronic liver di sease, Methods: We studied 48 patients with chronic liver disease who had varying degrees of liver fibrosis, graded 0-6 using a modified Kno dell score, and 20 control subjects without liver disease, Urinary DES (mu g/g creatinine) and HP (nmol/mmol creatinine) were measured by an isotope dilution, high performance liquid chromatography method, For liver disease patients, aminoterminal propeptide of type III procollag en (PIIINP) and alanine aminotransferase were determined, The urine an d serum markers were correlated to degree of fibrosis and inflammation on liver biopsies, Differences between groups were analyzed by ANOVA and multiple linear regression was applied determine independence of v ariables, Sensitivity, specificity and receiver operating curves were derived for each marker. Results: In the 17 patients with liver fibros is score of 5-6, mean urinary DES, IDES, KP and LP were all significan tly greater than in the control group (p<0.05), Urinary DES and IDES c orrelated best with fibrosis score, r=0.61 for both markers. The corre lation coefficient between serum PIIINP and fibrosis score was 0.47, U rinary DES and HP each had an overall diagnostic accuracy of 77% for f ibrosis. Combining markers improved accuracy to over 80%. No correlati on was seen between the urinary markers and inflammation scores. Concl usions: Urinary DES and HP are potentially useful clinical markers for liver fibrosis, especially when used in combination or in association with PIIINP.