Serum type III procollagen aminopeptide for assessing liver damage in methotrexate-treated psoriatic patients.
This study was designed to establish whether measurement of a serological marker of fibrosis might reduce the need for liver biopsy in psoriatic patients receiving methotrexate (MTX). Levels of type III procollagen aminopeptide (PIIINP-O and PIIINP-B) and laminin P1 (LamP1-B) were measured in 147 serum samples taken at the time of liver biopsy in 87 patients receiving long-term MTX treatment for severe psoriasis. Biopsies were classified as: (1) normal, (2) steatosis, (3) inflammation, (4) fibrosis, or (5) cirrhosis. Groups 3-5 were considered to show clinically relevant abnormality. Compared with controls, PIIINP-O was significantly raised in the group of MTX-treated psoriatics (P < 0.001). Within this group, levels were significantly higher in patients with inflammation, fibrosis or cirrhosis compared with those with normal histology or steatosis alone (P < 0.0001). In contrast, PIIINP-B and LamP1-B did not distinguish between controls and MTX-treated patients or between histological groups. Forty-two patients had two or more biopsies with simultaneous PIIINP-O measurement. PIIINP-O levels at the time of the first biopsy were normal in six of the seven patients whose histology was initially normal and subsequently became abnormal. A single measurement of PIIINP-O thus did not predict which patients might develop abnormal histology following further MTX. In a group of 17 patients, PIIINP-O was measured 3-monthly for up to 6 years during MTX treatment. PIIINP-O was elevated at some time during follow-up in all three patients who developed abnormal histology but was consistently normal in eight of the 11 patients whose histology remained or became normal. Our findings indicate that PIIINP-O is of value in detecting liver damage and, particularly if measured serially, may reduce the need for liver biopsy in MTX-treated patients. Although the test does not detect all patients with fibrosis, it would appear that the risk of missing significant liver damage in patients with persistently normal PIIINP-O is low.
Dermatology Centre, University of Manchester School of Medicine, U.K.
M J
MJ
Boffa
A
A
Smith
R J
RJ
Chalmers
D M
DM
Mitchell
B
B
Rowan
T W
TW
Warnes
M
M
Shomaf
N Y
NY
Haboubi
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury; D003879:Dermatologic Agents / Q000009:adverse effects*; D005500:Follow-Up Studies; D006801:Humans; D007797:Laminin / Q000097:blood; D008107:Liver Diseases / Q000097:blood / Q000175:diagnosis*; D008727:Methotrexate / Q000009:adverse effects*; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*; D011347:Procollagen / Q000097:blood*; D011565:Psoriasis / Q000188:drug therapy; D012680:Sensitivity and Specificity
D015415:Biomarkers; D003879:Dermatologic Agents; D007797:Laminin; D010446:Peptide Fragments; D011347:Procollagen; C055716:laminin P1; C041876:procollagen Type III-N-terminal peptide; D008727:Methotrexate