Rheumatoid arthritis

Which screening test is best for liver fibrosis in patients treated with MTX?


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, an Australian study shows.

Published in the Internal Medicine Journal, the WA study 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.

Potentially significant fibrosis was identified 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 which the investigators said was suggestive of at least moderate liver fibrosis.

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 authors said.

Hepascore had a sensitivity of 100% and specificity of 64% respectively 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.”

They suggested some of the screening tests may not be a reliable indicator of fibrosis in RA patients treated with methotrexate.

For example, 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.

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

Senior investigator Associate Professor Helen Keen, from the Fiona Stanley Hospital, told the limbic that effective monitoring for hepatotoxicity was important because methotrexate was a drug used as a first line treatment for people with RA.

“The prevalence of RA in Australia is estimated at about 2% so that’s a common disease and if all of them are on methotrexate then even when it is a rare complication, it’s not unusual.”

“And the other thing is that most of these people will be on this drug for life if they can tolerate it. So we certainly want to minimise the risk of harm.”

She said most guidelines for the use of methotrexate only recommended monitoring liver transaminases.

“But we certainly shouldn’t be doing the things we normally do which is measuring liver function tests. And normally that is just ALT, we don’t even measure their AST generally. If you just ask for liver function, our lab doesn’t give an AST which is certainly more specific than ALT.”

“And then we shouldn’t do an ultrasound because that is not particularly good for detecting fibrosis.”

Associate Professor Keen said the FIB-4 was probably a good screening test before moving onto a FibroScan.

“You want to have screening tests that are cheap and easy to do. That’s why FIB-4 may be better but we do need to redo the study in a more generalised population to confirm our findings.”

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