title: Liver stiffness correlates with methotrexate cumulative dose in patients with rheumatoid arthritis.
abstract: BACKGROUND
  Liver stiffness values were recently proposed to identify patients with methotrexate-induced liver fibrosis. Aim of this study was to assess the clinical and laboratory determinants of the association between liver stiffness, measured by transient elastography, and methotrexate treatment in patients with rheumatoid arthritis in the absence of other factors contributing to liver damage and fibrosis.
  
  
  METHODS
  100 patients with rheumatoid arthritis, with a cumulative methotrexate dose ranging from 1530 to 13,000 mg over a mean period of 7.07±3.89 yrs, were retrospectively evaluated.
  
  
  RESULTS
  The average liver stiffness value in the whole population was 4.93±1.8 kPa, excluding the presence of significant fibrosis. At univariate analysis, a significant correlation was found between liver stiffness and methotrexate cumulative dose, duration of treatment, alanine transaminases levels, body mass index, gamma glutamyl-transpeptidase and the presence of steatosis. At multivariate analysis, a significant association was detected only between liver stiffness and methotrexate cumulative dose. Out of 11 patients with liver stiffness >7.0 kPa, five were subjected to liver biopsy and mild or moderate perisinusoidal fibrosis was detected in two patients with a cumulative dose >4000 mg and liver stiffness >9 kPa.
  
  
  CONCLUSIONS
  Chronic methotrexate treatment induces a progressive increase in liver stiffness corresponding to mild or moderate perisinusoidal fibrosis for values >9 kPa.
authors.affiliation: Dipartimento di Medicina Interna, Università degli Studi di Firenze/Azienda Ospedaliero Universitaria Careggi (AOUC), Firenze, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Arena
authors.forename: Cristina
authors.initials: C
authors.lastname: Stasi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mannoni
authors.forename: Maurizio
authors.initials: M
authors.lastname: Benucci
authors.forename: Susanna
authors.initials: S
authors.lastname: Maddali-Bongi
authors.forename: Daniele
authors.initials: D
authors.lastname: Cammelli
authors.forename: Ali
authors.initials: A
authors.lastname: Assarat
authors.forename: Fabio
authors.initials: F
authors.lastname: Marra
authors.forename: Massimo
authors.initials: M
authors.lastname: Pinzani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004548:Elasticity; D054459:Elasticity Imaging Techniques; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000503:physiopathology*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D018501:Antirheumatic Agents; D008727:Methotrexate