IBD preclinical phase may start eight year before symptoms


By Mardi Chapman

9 Nov 2023

Widespread changes in biochemical and haematological parameters occur up to eight years before an IBD diagnosis supporting the existence of a long suspected extended preclinical phase, researchers say.

But the ‘subtle’ changes do not lend themselves to accurate early identification of people at risk of IBD, according to the authors of a Danish study.

Published in Cell Reports Medicine [link here], the study analysed pre-diagnosis results across 17 routine blood tests from a nationwide cohort of about 20,000 IBD patients and 4.6 million controls.

Tests included CRP, a differential blood cell count, platelet count, haemoglobin, iron, folate, vitamins B12 and D, liver enzymes and a faecal calprotectin ordered by GPs or at non-hospital clinics.

The study investigators found 16 of 17 tests at baseline showed statistically significant differences between Crohn’s disease (CD) cases and controls and between ulcerative colitis (UC) cases and controls.

“When analysing results over time, 12 of 17 tests also showed time-dependent differences—implying that there were temporal trends in test results within the pre-diagnostic period that differed between individuals who developed CD and controls,” they wrote.

For ulcerative colitis, 15 of 17 tests showed time-dependent differences.

The largest differences in test results were seen in the year immediately preceding an IBD diagnosis and the association tended to weaken at earlier time points.

“However, 8 years before a diagnosis of CD, levels of leukocytes, neutrophils, and platelets remained significantly higher in CD cases compared to controls,” the study authors said.

“Seven years before CD diagnosis, levels of CRP were also higher, while levels of haemoglobin were lower. 5 years before CD diagnosis, levels of monocytes were higher in cases than controls, while levels of iron, albumin, and bilirubin were lower.”

The study found a much shorter period with detectable differences between blood tests for UC cases and controls.

“For example, 3 years before UC diagnosis, cases had higher levels of CRP, leukocytes, neutrophils, eosinophils, and platelets compared to controls, but these differences were not apparent at earlier time points.”

It found that the median values for all blood tests were within their respective normal ranges.

“This suggests that while pre-diagnostic results in future IBD patients may have significantly differed from controls, these results would generally not have been considered abnormal,” the study said.

The investigators said their findings, from the largest objective study of its kind, suggest that IBD initiation is likely to begin far earlier than previously thought, especially in CD.

“This has important implications for the future development of strategies aimed at preventing the onset of disease and conversely highlights a considerable window of opportunity that could be targeted pharmacologically for early therapy or by addressing modifiable risk factors (e.g., smoking and diet).”

The study found a combination of tests – CRP, neutrophils, monocytes, platelets, haemoglobin, and eosinophils – only had a modest ability to predict an IBD diagnosis.

“It is not known whether the changes we detect in the pre-clinical phase of IBD are specific to IBD or would also be seen in other inflammatory disorders, e.g., rheumatoid arthritis,” it said.


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