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PROCOLLAGEN PEPTIDE SERUM LEVELS IN CHRONIC LIVER DISEASE: COMPARISON OF ANTIBODY - AND FAB - RADIOIMMUNOASSAYS FOR ASSESSMENT OF LIVER FIBROSIS P.Y. Zauqq, K. WeiqaDd, *A. Zimmermann, R. Preisig, Departments of Clinical Pharmacology and of *Pathology, University of Berne, Switzerland

Procollagen peptide (PP) serum levels have been shown to be re l i ab le indicators of f ibros is in chronic l i ve r disease. Hitherto, the i r measurement was cumbersome, since with the antibody(Ab)-RIA a serum d i l u t i on curve had to be obtained for each sample. Recently, a Fab-RIA (Hoechst) with ident ica l a f f i n i t y to PP and i ts degradation product Col-I was developed permitt ing measurement by single d i l u t i on . To assess the i r c l i n i ca l signif icance, PP-Fab determinations were compared with PP-Ab results in 12 healthy volunteers (HV), 8 subjects with fa t t y l i ve r (FL) and 47 patients with biopsy documented chronic l i ve r disease: I0 a lcohol ic (AC), I I posthepatic and 12 primary b i l i a r y c i r rhot ics , I0 chronic active and 4 chronic persistent hepat i t is . Reproducibi l i ty of PP-Fab results was excel lent with coef f ic ients of var ia t ion in te r - and intra-assay of 7 and I0 %, respectively. In subjects with nonf ibrot ic FL, PP-Fab levels (49 + S.D, 9.5 ng/ml) were comparable to those in HV (47 + 5.9); in f i b r o t i c l i ve r diseases, on the other hand, PP-Fab concentrations were on the average elevated with highest mean values (88 ± 30) achieved in AC. Interest ingly , a l l 8 patients studied under immunosuppressive treatment (prednisone, azathioprine, penici l lamine or combinations thereof) had PP-Fab levels within control range. PP-Fab levels correlated s ign i f i can t l y (r=0.69) with PP-Ab concentrations. More important, in the 30 patients where morphometric measurements of l i ve r biopsies were avai lable, PP-Fab levels showed a close re lat ionship with portal t rac t area (r=O.80) and with number of f ibroblasts (Rs=O.68). Thus, the Fab-RIA may become the f i r s t serum test sui table for c l i n i ca l routine with PP-Fab concentrations y ie ld ing semiquantitat ive information on extent and ac t i v i t y of l i ve r f ibros is .

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PROCOLLAGEN PEPTIDE (PP) SERUM LEVELS IN CHRONIC LIVER DISEASE: LO~G TERM FOLLOW-UPS WITH ANTIBODY (Ab)- AND FAB - RIA. P. Y. Zau~, K. Wei~and, Department of Clinical Pharmacology, Uni- versity of Berne, Switzerland

As previous studies have shown, PP reflects fibrotic activity of the liver and may be helpful in the follow-up of patients with chronic liver disease. The available antibody reacts with PP and its degradation product col i. Since the affinity to the latter is 1/10 only, a serum dilution curve has to be obtained for each individual sample. Recently, a Fab-RIA was developed with identical affinity to both PP's, allowing measurement by single dilution. Furthermore, simultaneous determination of Ab- and Fab-PP may give information on the degra- dation of PP in liver disease. Therefore, PP was measured sequentially in 18 pat with chronic liver disease for 3.7 ~ SD 1.8 years with both assays. All pat had at least one biopsy. Nine of 11 with CAH had histological signs of fibrosis or cirrhosis, 5 had PBC, and 2 alcoholic cirrhosis. In 9 both, Ab- and Fab-PP, were always elevated, in 6 Fab was normal or fluctuated around the upper limit of normal whereas Ab-PP was slightly elevated. In all 15 pat the ratio Ab/FAB remained constant in the range of 0.2 - 0.4. However, in 2 pat during immuno- suppresive therapy and in one during treatment with the antifibrotic drug malo- tilate, Fab and Ab diverged and the ratio decreased remarkably. In conclusion: In the majority of patients Fab and Ab- PP changed in parallel, indicating a steady state between release and degradation of PP. The Fab-assay, suitable for routine use, may therefore replace the Ab-RIA. In a few p@t, the degradation of PP seems to be disturbed and it is tempting to speculate that this is related to treatment. Its clinical significance, however, remains to be investigated.

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