Background/Purpose: Methotrexate ( MTX ) is an anchor drug in the treatment of Rheumatoid ( RA ) and Psoriatic arthritis ( PSA )and is the first line therapy in RA according to international guidelines and recommendations. However, there is constant concern on drug related hepatoxicity in long term use, particularly in patients with psoriasis. Guidelines had laid out the need for liver biopsy depending on the cumulative methotrexate dose but were controversial as liver biopsy itself carries considerable risk. Fibroscan ( transient elastography TE ) is a newly developed non-invasive technique to examine liver stiffness and hence liver fibrosis. Validation and correlations have been made in various liver diseases for fibrosis and cirrhosis detection and screening.

Methods: RA and PsA patients in a local rheumatology clinic were recruited. Patients with known pre-existing liver diseases were excluded. Demographic variables including age, sex, alcohol use, disease characteristics, concurrent co-morbidities, cumulative and duration of MTX use were recorded. TE were performed on these patients and liver stiffness were measured. A stiffness level of 7.9 kPa was used as cut off value as probable significant liver fibrosis and liver biopsy was offered.

Results: A total of 50 PsA and 215 RA patients were contacted and 128 ( 33 PsA,95 RA ) of them were eligible for TE. Average disease duration was 8 years ( SD 6.2 ). Mean cumulative MTX dose was 2427.3 mg ( SD 2330.6 ). 55 % of patients had cumulative dose of MTX > 1500 mg and 21 % had cumulative dose of MTX > 3500 mg. Mean duration of MTX use was 4.2 years ( SD 3.59 ). PsA patients had higher body mass index ( 25.2 vs 23.2, p=0.02 ), higher percentage of insulin resistance ( 45.5 vs 21.1 %, p=0.07 ) and abnormal HDL cholesterol level ( 63.3 vs 37.9 %, p=0.01 ) at baseline but lower cumulative MTX dose use ( 1775 mg vs 2654 mg, p=0.06 ) than RA patients. Mean liver stiffness was significantly lower in RA- 4.67kPa ( SD 1.42 ) than in PsA patients- 5.67 kPa ( SD 3.34 ). In univariate analysis, liver stiffness determined by TE was found to be positively associated with the presence of psoriasis, age, insulin resistance, hypertension, metabolic syndrome and duration of MTX use. However, only presence of psoriasis (β=0.947; p=0.022), insulin resistance (β=0.815; p=0.043) and age ( β=0.058; p<0.001) was found to be significant associative factors on multivariate analysis. At a cutoff point of 7.9 kPa, only 4.9 % of patients ( 3 RA and 3 PsA ) had probable significant fibrosis. All 6 patients had cumulative MTX dose > 1500 mg. However, logistic regression analysis only found that hypertension ( OR= 11.02, 95% CI: 1.13-107.5, p= 0.039) to be an independent risk factor for development of significant fibrosis. There is no correlation of MTX dose, duration of MTX use, and disease entity with significant fibrosis. 2 of these 6 patients had liver biopsies performed showing mild peri-portal fibrosis and steatosis.

Conclusion: PsA patient on MTX had higher liver stiffness than RA patients on TE. However, significant liver fibrosis was not common in these patients on methotrexate. Cumulative dose of MTX was probably not related to the development of significant liver fibrosis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/prevalence-and-predictors-of-significant-liver-fibrosis-in-methotrexate-treated-rheumatoid-and-psoriatic-arthritis-patients-using-transient-elastography-fibroscan/