P417 Non-invasive assessment of liver fibrosis by transient elastography and AST to ALT ratio in patients with Crohn's disease treated with methotrexate

Abstract

Background: One of the most feared concerns about the use of methotrexate (MTX) is the risk of developing chronic liver injury. Transient elastography is a simple, non-invasive method for estimating liver fibrosis. AST to ALT ratio (AST/ALT ratio) is also a good easy-to-use indicator of the risk of fibrosis in chronic liver diseases. The aim was to assess the risk of chronic liver injury induced by MTX in a cohort of patients with Crohn's disease (CD) at a high-volume tertiary center. Methods: Cross-sectional study including CD patients treated with methotrexate. Clinical and laboratorial data, duration of treatment, and cumulative dose of methotrexate were obtained. Liver stiffness was assessed by FibroScan®, and the cutoff values for significant liver fibrosis (according to METAVIR) was F ≥2: 7.1 kPa. AST/ALT ratio was considered significant for risk of fibrosis if >1. Patients with chronic hepatitis B or C, excessive daily consumption of alcoholic, non-alcoholic steatohepatitis, or other known causes of chronic liver disease were excluded. Estimates of the presence and severity of steatosis according to the parameter of controlled attenuation (CAP) were also evaluated, considering the absence of significant steatosis (S0) if less than 200 dB/m, mild (S1) if 200–249 dB/m, moderate (S2) if 250–299 dB/m, and severe (S3) if 300 dB/m or greater. Results: 62 patients were included, 35 female (56.5%), with a mean age of 37.5±11.3 years. MTX was the first-line immunosuppressant in 9 patients (14.5%). Indications for initiating MTX included: adjuvant to anti-TNF agent (43.5%), intolerance to azathioprine (27.4%), corticodependence (19.4%) and corticoresistance (9.7%). Mean treatment duration was 88±86 weeks. Mean cumulative MTX dose was 998±871 mg. All patients received MTX subcutaneously. In sixteen patients MTX was discontinued due to changes in liver function tests. The mean value of Fibroscan was 5.3±1.5 kPa, and in 11.1% of cases the value was considered significant for fibrosis (≥7.1 kPa). In none of the cases was a value compatible with METAVIR F4 (>11 kPa). The mean CAP value was 198±58 dB/m, distributed as follows: S0 63.3%, S1 16.7%, S2 13.3% and S3 6.7%. The mean AST/ALT ratio was 1.12±0.43 and was considered significant (>1) in 58.7% of the cases. Fibroscan values correlated directly with ALT (0.44, p=0.026) and bilirubin (0.426, p=0.038), but not with duration of treatment or cumulative dose. Likewise, these variables did not correlate with the AST/ALT ratio. Conclusions: Excluding patients with other risk factors for chronic liver disease, the use of methotrexate regardless of the cumulative dose appears to be safe in the medium to long term in CD patients according to non-invasive methods.