Arthritis a clue to liver fibrosis in HFE haemochromatosis

Arthritis, one of the first clinical manifestations in HFE haemochromatosis, predicts the likelihood of advanced hepatic fibrosis.

A retrospective of 112 HFE haemochromatosis subjects with liver biopsy-validated fibrosis from a Queensland cohort found arthritis – defined as type 2 polyarticular arthritis​​ involving metacarpophalangeal joints or bilateral large joint arthropathy – was present in 34% of males and 8% of females.

Over 90% of subjects with arthritis had joint disease involving the metacarpophalangeal joints.

The study, published in Mayo Clinic Proceedings, found there was a significant association between liver biopsy-proven advanced hepatic fibrosis and arthritis (p<0.001)

Sixteen of 19 subjects (84%) with F3-4 fibrosis had arthritis. Thirty-one of 93 subjects (33%) who had F0-2 fibrosis had arthritis.

“Arthritis had 84% sensitivity (SENS), 67% specificity (SPEC), 34% positive predictive value (PPV), 95% negative predictive value (NPV) and a relative risk of 7.4 (95% CI 2.5-23) for detecting F3-4 fibrosis,” the study said.

Arthritis provided a risk ratio of 4.5 for the presence of an AST to platelet ratio (APRI) >0.44 however arthritis exhibited limited utility for detection of advanced hepatic fibrosis using the FIB-4 index.

Co-author Professor John Olynyk, from the South Metropolitan Health Service in WA, told the limbic the findings were relevant in practice.

“Here we are saying that if you have arthritis then you are most at risk for getting liver disease and if you have liver disease, well it tends to associate very strongly with arthritis. So they tend to travel together as a pair.”

So clinicians could advise patients without arthritis that they were highly unlikely to develop severe liver disease.

“The absence of arthritis predicts a low likelihood of advanced hepatic fibrosis, supporting its use as a clinical marker for advanced hepatic fibrosis in HFE haemochromatosis,” the study said.

“We recommend that all HFE haemochromatosis subjects with arthritis undergo evaluation for advanced hepatic fibrosis either using liver biopsy or noninvasively using APRI.”

“Furthermore, those HFE haemochromatosis subjects who do not have arthritis are at low risk of advanced hepatic fibrosis and may avoid further invasive investigation in the form of liver biopsy.”

The study also supported relatively recent findings that patients with arthritis had elevated erythrocyte mean corpuscular volume (MCV).

The current study found MCV values were significantly higher in those subjects with F3-4 fibrosis compared with the F0-2 fibrosis group (P=.004).

“Thus, the association between arthritis and F3-4 fibrosis is reflected in the relationship between both these clinical entities and the MCV. The biological processes which underlie this observation remains unclear,” it said.

Professor Olynyk said in patients of Northern European origin presenting with arthritis, clinicians should consider haemochromatosis and order iron tests in the first instance.

“The arthritis can come on early in the disease before liver disease, it can go on after the patients has been diagnosed and treated, and it can come on anytime in between.”

The study said arthritis was clinically useful in HFE haemochromatosis because it was not always associated with iron deposition or improved by therapeutic phlebotomy whereas liver injury was.


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