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Procollagen peptide serum levels in chronic liver disease: Comparison of antibody — And FAB — Radioimmunoassays for assessment of liver fibrosis
345
PROCOLLAGEN PEPTIDE SERUM LEVELS IN CHRONIC LIVER DISEASE: COMPARISON OF ANTIBODY AND FAB - RADIOIMMUNOASSAYSFOR ASSESSMENTOF 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 r e l i a b l e indicators of f i b r o s i s in chronic l i v e r disease. Hitherto, t h e i r measurement was cumbersome, since with the antibody(Ab)-RIA a serum d i l u t i o n curve had to be obtained f or each sample. Recently, a Fab-RIA (Hoechst) with i d e n t i c a l a f f i n i t y to PP and i t s degradation product Col-I was developed permitting measurement by single d i l u t i o n . To assess t h e i r c l i n i c a l significance, PP-Fab determinations were compared with PP-Ab results in 12 healthy volunteers (HV), 8 subjects with f a t t y l i v e r (FL) and 47 patients with biopsy documented chronic l i v e r disease: I0 a l c o h o l i c (AC), I I posthepatic and 12 primary b i l i a r y c i r r h o t i c s , I0 chronic active and 4 chronic persistent h e p a t i t i s . R e p r o d u c i b i l i t y of PP-Fab results was e x c e lle n t with c o e f f i c i e n t s of v a r i a t i o n i n t e r - and intra-assay of 7 and I0 %, respectively. In subjects with n o n f i b r o t i c 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 v e r diseases, on the other hand, PP-Fab concentrations were on the average elevated with highest mean values (88 ± 30) achieved in AC. I n t e r e s t i n g l y , a l l 8 patients studied under immunosuppressive treatment (prednisone, azathioprine, penicillamine or combinations thereof) had PP-Fab levels within control range. PP-Fab levels correlated s i g n i f i c a n t l y (r=0.69) with PP-Ab concentrations. More important, in the 30 patients where morphometric measurements of l i v e r biopsies were a v a i l a b l e , PP-Fab levels showed a close r e l a t i o n s h i p with portal t r a c t area (r=O.80) and with number of f i b r o b l a s t s (Rs=O.68). Thus, the Fab-RIA may become the f i r s t serum test suitable f o r c l i n i c a l routine with PP-Fab concentrations y i e l d i n g semiquantitative information on extent and a c t i v i t y of l i v e r fibrosis.
P R O C O L L A G E N PEPTIDE (PP) SERUM LEVELS IN CHRONIC LIVER DISEASE: TERM F O L L O W - U P S WITH A N T I B O D Y (Ab)- AND FAB - RIA. P. Y. Z a u ~ , K. Wei~and, D e p a r t m e n t of Clinical Pharmacology, University of Berne, S w i t z e r l a n d LO~G
346
As p r e v i o u s 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 a n t i b o d y reacts w i t h PP and its d e g r a d a t i o n product col i. Since the affinity to the latter is 1/10 only, a serum d i l u t i o n curve has to be o b t a i n e d for each individual sample. Recently, a Fab-RIA was d e v e l o p e d with identical affinity to both PP's, a l l o w i n g m e a s u r e m e n t by single dilution. Furthermore, simultaneous d e t e r m i n a t i o n of Ab- and Fab-PP may give information on the degradation of PP in liver disease. Therefore, PP was m e a s u r e d 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 h i s t o l o g i c a l 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 A b - P P was slightly elevated. In all 15 pat the ratio Ab/FAB remained c o n s t a n t in the range of 0.2 - 0.4. However, in 2 pat during immunosuppresive therapy and in one during treatment with the antifibrotic drug malotilate, Fab and Ab d i v e r g e d and the ratio d e c r e a s e d remarkably. In conclusion: In the m a j o r i t y of p a t i e n t s Fab and Ab- PP changed in parallel, indicating a steady state between release and d e g r a d a t i o n 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 d i s t u r b e d and it is tempting to speculate that this is related to treatment. Its clinical significance, however, remains to be investigated.
S351
PROCOLLAGEN PEPTIDE SERUM LEVELS IN CHRONIC LIVER DISEASE: COMPARISON OF ANTIBODY AND FAB - RADIOIMMUNOASSAYSFOR ASSESSMENTOF 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 r e l i a b l e indicators of f i b r o s i s in chronic l i v e r disease. Hitherto, t h e i r measurement was cumbersome, since with the antibody(Ab)-RIA a serum d i l u t i o n curve had to be obtained f or each sample. Recently, a Fab-RIA (Hoechst) with i d e n t i c a l a f f i n i t y to PP and i t s degradation product Col-I was developed permitting measurement by single d i l u t i o n . To assess t h e i r c l i n i c a l significance, PP-Fab determinations were compared with PP-Ab results in 12 healthy volunteers (HV), 8 subjects with f a t t y l i v e r (FL) and 47 patients with biopsy documented chronic l i v e r disease: I0 a l c o h o l i c (AC), I I posthepatic and 12 primary b i l i a r y c i r r h o t i c s , I0 chronic active and 4 chronic persistent h e p a t i t i s . R e p r o d u c i b i l i t y of PP-Fab results was e x c e lle n t with c o e f f i c i e n t s of v a r i a t i o n i n t e r - and intra-assay of 7 and I0 %, respectively. In subjects with n o n f i b r o t i c 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 v e r diseases, on the other hand, PP-Fab concentrations were on the average elevated with highest mean values (88 ± 30) achieved in AC. I n t e r e s t i n g l y , a l l 8 patients studied under immunosuppressive treatment (prednisone, azathioprine, penicillamine or combinations thereof) had PP-Fab levels within control range. PP-Fab levels correlated s i g n i f i c a n t l y (r=0.69) with PP-Ab concentrations. More important, in the 30 patients where morphometric measurements of l i v e r biopsies were a v a i l a b l e , PP-Fab levels showed a close r e l a t i o n s h i p with portal t r a c t area (r=O.80) and with number of f i b r o b l a s t s (Rs=O.68). Thus, the Fab-RIA may become the f i r s t serum test suitable f o r c l i n i c a l routine with PP-Fab concentrations y i e l d i n g semiquantitative information on extent and a c t i v i t y of l i v e r fibrosis.
P R O C O L L A G E N PEPTIDE (PP) SERUM LEVELS IN CHRONIC LIVER DISEASE: TERM F O L L O W - U P S WITH A N T I B O D Y (Ab)- AND FAB - RIA. P. Y. Z a u ~ , K. Wei~and, D e p a r t m e n t of Clinical Pharmacology, University of Berne, S w i t z e r l a n d LO~G
346
As p r e v i o u s 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 a n t i b o d y reacts w i t h PP and its d e g r a d a t i o n product col i. Since the affinity to the latter is 1/10 only, a serum d i l u t i o n curve has to be o b t a i n e d for each individual sample. Recently, a Fab-RIA was d e v e l o p e d with identical affinity to both PP's, a l l o w i n g m e a s u r e m e n t by single dilution. Furthermore, simultaneous d e t e r m i n a t i o n of Ab- and Fab-PP may give information on the degradation of PP in liver disease. Therefore, PP was m e a s u r e d 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 h i s t o l o g i c a l 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 A b - P P was slightly elevated. In all 15 pat the ratio Ab/FAB remained c o n s t a n t in the range of 0.2 - 0.4. However, in 2 pat during immunosuppresive therapy and in one during treatment with the antifibrotic drug malotilate, Fab and Ab d i v e r g e d and the ratio d e c r e a s e d remarkably. In conclusion: In the m a j o r i t y of p a t i e n t s Fab and Ab- PP changed in parallel, indicating a steady state between release and d e g r a d a t i o n 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 d i s t u r b e d and it is tempting to speculate that this is related to treatment. Its clinical significance, however, remains to be investigated.
S351