QUANTITATIVE LIVER-FUNCTION IN PATIENTS WITH RHEUMATOID-ARTHRITIS TREATED WITH LOW-DOSE METHOTREXATE - A LONGITUDINAL-STUDY

The objectives were to determine quantitative liver function prospecti vely in patients with rheumatoid arthritis (RA) treated with low-dose methotrexate (MTX), to search for risk factors for a loss of quantitat ive 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 galac tose elimination capacity (GEC), aminopyrine breath test (ABT) and liv er enzymes [aspartate amino transferase (AST), alanine amino transfera se (ALT), alkaline phosphatase (AP), gamma-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/mi n/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)], signific ant declines of GEC (-0.12 mg/min/kg per year, t = 3.30, P < 0.002) an d ABT (-0.06%kg/mmol per year, t = 4.81, P < 0.001) were observed. Neg ative correlations were found between the annual change in GEC and GEC at baseline (R-S = -0.40, P < 0.0001), and the annual change in ABT a nd ABT at baseline (R-S = -0.43, P < 0.0001). No correlations were fou nd 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 Roen igk grade III had impaired quantitative liver function, while 14 patie nts with Roenigk grades I and II exhibited a high variability of GEC a nd ABT from normal to abnormal values. The continuous declines in GEC and ABT observed deserve attention in patients with prolonged treatmen t. Patients with a low GEC or ABT at baseline seem not to be at increa sed risk for a further loss of quantitative liver function. An impaire d GEC or ABT does not necessarily concur with hepatic fibrosis on hist ological examination.