title: Methotrexate-induced liver cirrhosis. Clinical, histological and serological studies--a further 10-year follow-up.
abstract: BACKGROUND
  Methotrexate (MTX) may induce liver damage, which in some psoriatics will lead to fibrosis or cirrhosis. Studies performed 10 years ago on 25 patients with MTX-induced liver cirrhosis indicated that this type of cirrhosis was not of an aggressive nature.
  
  
  OBJECTIVE
  The aim of this study was to evaluate the present status of surviving patients 10 years later, together with the latest clinical and histological data on patients who had died.
  
  
  METHODS
  The investigations were carried out on 186 liver biopsies and 5 autopsies. All biopsies were studied by the same pathologist. Eleven surviving patients were also studied by analysis of serum aminoterminal propeptide of type III procollagen (PIIINP), which is an indicator of fibrogenesis, which is especially suitable for follow-up of fibrotic liver disease.
  
  
  RESULTS
  Thirteen patients had died; 1 of these died of liver failure. Another patient died form an overdose due to misunderstanding of the prescribed dosage given elsewhere. The remaining deaths were non-MTX related, but all 5 autopsies showed some degree of cirrhosis. On the other hand, 13 patients had no histologically verified liver cirrhosis in their latest biopsy, and PIIINP was within the normal range in all 11 patients investigated, this in spite of total cumulative MTX doses from 1,120 to 18,645 mg (mean 7,171 mg).
  
  
  CONCLUSIONS
  This study confirmed that in most patients MTX-induced liver cirrhosis is not aggressive. However, continued low-dose MTX led, in spite of normal liver tests, 8 years after the last biopsy to liver failure and death in 1 of our patients. Our data support the continued use of liver biopsies in the surveillance of MTX-treated psoriatics.
authors.affiliation: Department of Dermatology, Marselisborg Hospital, University of Aarhus, Denmark.
authors.forename: H
authors.initials: H
authors.lastname: Zachariae
authors.forename: H
authors.initials: H
authors.lastname: Søgaard
authors.forename: L
authors.initials: L
authors.lastname: Heickendorff
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D003879:Dermatologic Agents / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000139:chemically induced*; D008297:Male; D008727:Methotrexate / Q000009:adverse effects*; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D011565:Psoriasis / Q000188:drug therapy
chemical_list: D015415:Biomarkers; D003879:Dermatologic Agents; D010446:Peptide Fragments; D011347:Procollagen; C041876:procollagen Type III-N-terminal peptide; D008727:Methotrexate