Methotrexate-induced liver fibrosis: The end of a long-held belief

Article Gastroenterology & Hepatology

Risk of liver fibrosis associated with long-term methotrexate therapy may be overestimated

Edmond Atallah et al.

Summary: This study evaluated the risk of long-term methotrexate (MTX) therapy on liver fibrosis using non-invasive markers and found that the risk attributed to MTX itself may have been overestimated, suggesting a need to modify current monitoring guidelines.

JOURNAL OF HEPATOLOGY (2023)

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Review Rheumatology

Busting the myth of methotrexate chronic hepatotoxicity

Vincent Di Martino et al.

Summary: Methotrexate is an important treatment for inflammatory rheumatic diseases, especially rheumatoid arthritis. Liver toxicity is a concern for long-term methotrexate therapy, particularly in patients with non-alcoholic fatty liver disease (NAFLD). Understanding the mechanisms of hepatotoxicity and liver fibrosis is crucial for pretreatment screening and long-term monitoring in patients with chronic liver disease.

NATURE REVIEWS RHEUMATOLOGY (2023)

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Article Rheumatology

Using FibroScan to Assess for the Development of Liver Fibrosis in Patients With Arthritis on Methotrexate: A Single-center Experience

Saman Darabian et al.

Summary: This study investigated the association between cumulative methotrexate (MTX) intake and liver fibrosis development using noninvasive transient elastography (FibroScan). The results showed no significant correlation between cumulative MTX dosage and liver stiffness, even at high doses of MTX. However, there was a significant correlation between body mass index (BMI) and FibroScan score.

JOURNAL OF RHEUMATOLOGY (2022)

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Review Medicine, General & Internal

Review of existing evidence demonstrates that methotrexate does not cause liver fibrosis

Hira Imad Cheema et al.

Summary: New evidence suggests that methotrexate may not directly cause liver injury but potentially mediates injury and fibrosis through non-alcoholic fatty liver disease. Meta-analysis did not find a statistically significant association between methotrexate dose and liver fibrosis. Existing evidence shows that advanced liver fibrosis and cirrhosis previously attributed to methotrexate are actually caused by metabolic liver disease or other chronic liver diseases.

JOURNAL OF INVESTIGATIVE MEDICINE (2022)

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Review Dermatology

Is methotrexate hepatotoxicity associated with cumulative dose? A systematic review and meta-analysis

Ali Azzam et al.

Summary: This synthesis reviewed 35 studies on the association between methotrexate hepatotoxicity and cumulative dose, finding that 38 analyses identified no significant association while 8 studies found a significant one. The pooled correlation coefficient from 5 studies using elastography showed limited correlation with significant heterogeneity between studies. This challenges the belief that liver injury is directly caused by drug accumulation.

AUSTRALASIAN JOURNAL OF DERMATOLOGY (2021)

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Review Pharmacology & Pharmacy