Transient elastography (TE) is a better screening tool for liver fibrosis when compared to Hepascore, FIB-4 or APRI in people with rheumatoid arthritis treated with methotrexate.

A WA study, published in the Internal Medicine Journal, recruited 56 patients with long-standing methotrexate use from outpatient general rheumatology and inflammatory arthritis clinics at a single tertiary centre from July 2017 to October 2018.

The study identified potential significant fibrosis in 18% of patients using TE, 4% using APRI, 36% using Hepascore and 2% using FIB-4. A small proportion of patients (7%) had ≥2 positive screening tests.

The majority of study participants had ALT and AST levels within the reference range.

Only one patient was considered to have significant clinical fibrosis out of 13 participants warranting referral for conventional liver ultrasound (US), shear wave elastography, comprehensive biochemical workup for liver disease and specialist hepatology review.

The patient had returned three out of six non-invasive liver fibrosis screening tests suggestive of at least moderate liver fibrosis.

The other patients reviewed by a hepatologist were deemed not to have significant fibrosis based on further testing.

The study found APRI had moderate correlation with FIB-4 and Hepascore but not with TE.

“TE exhibited 100% sensitivity and 84% specificity (p=0.029) for detecting hepatologist-diagnosed significant liver fibrosis, with APRI, Hepascore and FIB-4 performing less well,” the study said.

Hepascore had a sensitivity of 100% and specificity of 64% while FIB-4 and APRI both had 0% sensitivity and specificity of 96% and 93% respectively.

“Our findings are consistent with the current literature and suggest TE is a useful screening tool in RA patients on methotrexate.”

“To our knowledge, this is the first direct comparison of these screening tests for liver fibrosis together in RA subjects treated with methotrexate,” the investigators said.

“In our small cohort of patients with varying durations of methotrexate therapy, we found a high prevalence of suspected liver fibrosis using non-invasive screening, that was not confirmed on hepatologist assessment.”

The study authors noted that about 3% of patients treated with methotrextate may develop liver fibrosis, due to its mechanism of action  to inhibit dihydrofolate reductase and reduce intracellular stores of folic acid, affecting its role in the synthesis of purine and pyrimidine.

However, currently recommended screening tests such as LFTs may not be a reliable indicator of fibrosis in RA patients treated with methotrexate.

They noted that Hepascore may be falsely elevated since the algorithm includes hyaluronic acid in its calculation. Hyaluronic acid levels were found to be high in all patients with suspected liver fibrosis by Hepascore and in 80% of participants overall.

“APRI and FIB-4 also have the potential to be falsely elevated in patients with poor RA control due to platelets being an acute phase reactant and elevated in inflammation.”

However RA disease activity, as assessed by the DAS-28, did not correlate with any of the screening tests.

“Pragmatically, there is likely to be growth in the use of non-invasive liver fibrosis screening tests and it is important to understand the limitations of these in the assessment of subjects with RA,” the study said.

“Whilst the risk of MTX induced liver fibrosis remains low, given its seriousness, and the current widespread use of methotrexate, reliable screening for MTX induced liver fibrosis is required.”

“Further and larger studies would be useful to confirm these findings, ideally considering comparison against the gold standard of liver biopsy.”