Quantitative liver function in patients with rheumatoid arthritis treated with low-dose methotrexate: a longitudinal study.
The objectives were to determine quantitative liver function prospectively in patients with rheumatoid arthritis (RA) treated with low-dose methotrexate (MTX), to search for risk factors for a loss of quantitative liver function and to assess the relationship between quantitative liver function and histological staging. A total of 117 patients with RA (ACR criteria, 85 women, mean age 59 yr) had measurements of galactose elimination capacity (GEC), aminopyrine breath test (ABT) and liver enzymes [aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (AP), 7-glutamyl transferase (GGT), bile acids, bilirubin, albumin] before treatment with weekly i.m. MTX injections and every year thereafter. In 16 patients, liver biopsies were performed. Before the introduction of MTX, mean GEC was 6.6 mg/min/kg [5th to 95th percentile (5-95 PC) 5.1-8.5; reference range 6.0-9.1] and mean ABT was 0.80% kg/mmol (5-95 PC 0.42-1.30: reference range 0.6-1.0). During treatment with MTX [mean weekly dose 11.8 mg (5-95 PC 5.4-20.2), mean observation period 3.8 yr (5-95 PC 0.4-6.9)], significant declines of GEC (-0.12 mg/min/kg per year. t = 3.30, P < 0.002) and ABT (-0.06% kg/mmol per year, t = 4.81, P < 0.001) were observed. Negative correlations were found between the annual change in GEC and GEC at baseline (Rs = -0.40, P < 0.0001), and the annual change in ABT and ABT at baseline (Rs = -0.43, P < 0.0001). No correlations were found between the annual change in GEC or ABT and weekly MTX dose, age or percentage of increased liver enzymes, and no effect of a history of alcohol consumption > 30 g/week became evident. Two patients with Roenigk grade III had impaired quantitative liver function, while 14 patients with Roenigk grades I and II exhibited a high variability of GEC and ABT from normal to abnormal values. The continuous declines in GEC and ABT observed deserve attention in patients with prolonged treatment. Patients with a low GEC or ABT at baseline seem not to be at increased risk for a further loss of quantitative liver function. An impaired GEC or ABT does not necessarily concur with hepatic fibrosis on histological examination.
Beyeler
C
C
Department of Rheumatology, University of Berne, Switzerland.
Reichen
J
J
Thomann
S R
SR
Lauterburg
B H
BH
Gerber
N J
NJ
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D001219:Aspartate Aminotransferases / Q000097:blood; D001706:Biopsy; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D008875:Middle Aged; D012217:Rheumatoid Factor / Q000097:blood; D005723:gamma-Glutamyltransferase / Q000097:blood
D012217:Rheumatoid Factor; D003404:Creatinine; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D008727:Methotrexate