The value of amino-terminal propeptide of type III procollagen in routine screening for methotrexate-induced liver fibrosis: a 10-year follow-up.
BACKGROUND
Methotrexate (MTX) -induced liver damage is an important complication in patients treated with this drug for skin disease. Reliable non-invasive monitoring tests would have considerable importance.


OBJECTIVE
This retrospective study was designed in order to evaluate if serial normal serum levels of amino-terminal propeptide of type III procollagen (PIIINP) might indicate that no significant fibrosis is taking place in the liver, and thereby reduce the need for repeated liver biopsies in psoriatic patients treated with MTX.


METHODS
The clinical records of 70 patients with psoriasis, who in the years 1989/90 were on MTX and had both a liver biopsy without fibrosis and a normal PIIINP, were examined and followed until the patient stopped taking the drug. The follow-up time was from 1 to 11 years.


RESULTS
A total of 189 liver biopsies and 329 analyses of PIIINP were recorded. Twenty-one patients had only one and no further biopsies, but their data included at least two to three PIIINP samples obtained within a year around the time of the biopsy, and at least two were taken either prior to or at the time of the biopsy. The remaining patients had from two to seven liver biopsies each and a total of 267 analyses of PIIINP. In the study period only four patients developed fibrosis of the liver as shown by liver biopsies, and all four of these patients developed elevated serum PIIINP levels. In addition two further patients, one of them with psoriatic arthritis, had elevated PIIINP, but normal liver biopsy. Thus no liver fibrosis was missed in the 63 patients with consistently normal PIIINP levels.


CONCLUSIONS
Present data support the view that, as long as PIIINP is consistently normal in serial investigations, there is minimal risk of development of substantial liver fibrosis.
Zachariae
H
H
Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark. hzach@dadlnet.dk
Heickendorff
L
L
Søgaard
H
H
D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D003879:Dermatologic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000175:diagnosis / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000009:adverse effects* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000097:blood*; D011347:Procollagen / Q000097:blood*; D011565:Psoriasis / Q000188:drug therapy; D012189:Retrospective Studies
D015415:Biomarkers; D003879:Dermatologic Agents; D010446:Peptide Fragments; D011347:Procollagen; C041876:procollagen Type III-N-terminal peptide; D008727:Methotrexate