Serological markers for monitoring disease progression in noncirrhotic primary biliary cirrhosis on ursodeoxycholic acid therapy.
OBJECTIVE
Liver biopsy has so far been the only method to accurately follow the progression of primary biliary cirrhosis (PBC). The stage and the severity of lymphocytic piecemeal necrosis (LPN) have been shown to be an independent factor for the development of cirrhosis. In this 3-year prospective study, we evaluated the diagnostic value of several liver function tests, surrogate markers of fibrogenesis, hyaluronic acid (HA), procollagen III N-terminal peptide (S-PIIINP), cholestanol and plant sterols in noncirrhotic PBC patients treated with ursodeoxycholic acid (UDCA) or with UDCA and budesonide to assess the stage, inflammation and fibrosis.


METHODS
Seventy-seven stage I-III PBC patients were included into the study, with control biopsy at 36 months. Serum liver enzymes, bile acids (BA), HA, PIIINP, immunoglobulins, lipids and cholesterol precursors and plant sterols were measured at baseline and at 36 months.


RESULTS
Aspartate aminotransferase (AST), HA, BA and PIINP were significantly different between stages I to III and differentiated mild (F0F1) from moderate (F2F3) fibrosis. The combination of these variables (PBC score) exhibited best sensitivity and specificity, compared with AST/platelet ratio, Forns' score and fibrosis index. Using a cut-off value of 66 for the PBC score, the sensitivity was 81.4% and specificity was 65.2% for classifying the stage of PBC, regarding the stage the and fibrosis in noncirrhotic PBC.


CONCLUSIONS
Serum HA, BA, PIIINP and AST may serve as valuable simple tools to monitor the treatment response to UDCA in early stages of PBC. Combinations of these biomarkers into a single index further potentiate the diagnostic value of such measurements.
Färkkilä
Martti
M
Department of Medicine, Division of Gastroenterology, Helsinki University Central Hospital, Helsinki, Finland. martti.farkkila@hus.fi
Rautiainen
Henna
H
Kärkkäinen
Päivi
P
Karvonen
Anna-L
AL
Nurmi
Heimo
H
Niemelä
Onni
O
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D001647:Bile Acids and Salts / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D019819:Budesonide / Q000627:therapeutic use; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005355:Fibrosis / Q000097:blood / Q000473:pathology*; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy; D008111:Liver Function Tests; D010446:Peptide Fragments / Q000097:blood; D011237:Predictive Value of Tests; D011347:Procollagen / Q000097:blood; D011446:Prospective Studies; D012372:ROC Curve; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D001647:Bile Acids and Salts; D015415:Biomarkers; D002756:Cholagogues and Choleretics; D010446:Peptide Fragments; D011347:Procollagen; C041876:procollagen Type III-N-terminal peptide; D019819:Budesonide; D014580:Ursodeoxycholic Acid; D006820:Hyaluronic Acid; D001219:Aspartate Aminotransferases