Risk of liver fibrosis induced by methotrexate and other rheumatoid arthritis medications according to the Fibrosis-4 Index

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CER14239
2022 Vol.40, N°1
PI 0150, PF 0157
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PMID: 33938795 [PubMed]

Received: 18/11/2020
Accepted : 08/02/2021
In Press: 23/04/2021
Published: 28/01/2022

Abstract

OBJECTIVES:
We aimed to estimate the amount of scarring in the liver with the fibrosis-4 (FIB-4) index in patients with rheumatoid arthritis (RA) with special interest in methotrexate (MTX) influence.
METHODS:
This was a cross-sectional monocentric study including successive RA patients recruited for a 12-month period. Data on liver function, disease activity, hepatotoxic and cardiovascular risk factors were systematically collected. The FIB-4 index was calculated according the following formula: (age(years)× AST(U/L)/platelet (PLT) (109/L)×√ALT(U/L)).
RESULTS:
We included 170 patients with established RA: 141 (83%) were women with a mean age of 59±12 years and mean disease duration of 15±11 years. The FIB-4 was low and not significantly different between patients receiving MTX (n=102), patients previously treated with MTX (n=39) and patients never treated with MTX (n=29). No correlation was observed between FIB-4 values and cumulative MTX dose (r=0.09, p=0.271). No relationship was observed between FIB-4 and MTX treatment duration. The FIB-4 index was found significantly increased in patients receiving leflunomide (n=24), (median (range) 1.58 (0.46–3.16) vs. 1.18 (0.54–3.40), p=0.019) and tocilizumab (n=14), (median (range) 1.82 (0.75–3.73) vs. 1.18 (0.54–3.40), p=0.005) compared to patients not receiving DMARDs (n=29). Multivariate logistic regression analyses revealed an independent association between increased FIB-4 (>1.45) and male gender, low disease activity, and treatment with leflunomide and tocilizumab.
CONCLUSIONS:
RA patients with long-term maintenance MTX therapy have low FIB-4 values suggesting that MTX is not associated with an increased risk of advanced liver fibrosis. Increased FIB-4 values have been detected in leflunomide- and tocilizumab-treated patients, which will deserve dedicated further investigations.