Abstract
Inflammatory bowel disease (IBD) involves life-long chronic inflammation of the gastrointestinal tract. The diagnosis of IBD requires an endoscopic assessment, which is considered an invasive procedure. The long-term management of IBD is to work towards achieving and maintaining mucosal healing. Currently, this typically requires repeated endoscopic assessments. Other non-invasive tests such as blood and faecal tests that could be used in clinical practice as surrogate markers would reduce the need for endoscopy.
This thesis aimed to explore the perspectives of patients with regards to the current and potential tests used to monitor IBD, to evaluate the performance of combining faecal calprotectin (FCP) and standard blood results to improve detection of IBD in the current clinical practice, and to investigate the potential roles of five novel urinary and faecal biomarkers in IBD.
Two cross-sectional surveys explored the perspectives of New Zealand adults with IBD and parents of children with IBD on the current and potential IBD tests. Both surveys reported general blood tests were the most requested tests and had the highest completion rate, while medical imaging tests were the least ordered and most refused tests. Adults and parents preferred any test less invasive than colonoscopy for diagnosing or monitoring IBD.
Next, a study evaluated the performance of FCP in detecting IBD in children. Although FCP was a sensitive test in detecting IBD, two false-negative cases were identified. The positive predictive value (PPV) in diagnosing IBD was further improved if FCP was combined with albumin or platelet count compared to FCP alone.
Given adults and parents preferred non-invasive tests, a pilot study was conducted to evaluate the roles of four urinary novel biomarkers (intestinal fatty acid-binding protein (I-FABP), liver fatty acid-binding protein (L-FABP), claudin-3 and calprotectin) in young adults with active Crohn’s disease (CD). The study found urinary I-FABP may be a sensitive indicator of disease activity, and that urinary L-FABP may be a potential indirect nutritional marker. No role was identified for urinary claudin-3 or calprotectin.
The preliminary findings of urinary I-FABP led this thesis to extend the validation of this novel epithelial barrier biomarker together with another novel inflammatory biomarker, chitinase 3-like-1 protein (CHI3L1) in urine and faeces of children with and without IBD. Neither biomarker when assessed in urine was able to detect active IBD or detect clinical improvement in children with IBD who received remission treatment.
I-FABP and CHI3L1 were also evaluated in faeces from the same cohort of children and compared against FCP. While the faecal extraction process for I-FABP requires further optimisation before this protein can be considered further as a biomarker for IBD, CHI3L1 proved to be equally sensitive to FCP as a biomarker of inflammation. It is also a sensitive indicator of clinical improvement in children who received remission therapy. The combination of CHI3L1 and FCP biomarkers may improve the PPV in diagnosing IBD.
Non-invasive biomarkers play an essential role in the diagnosis and management of IBD. The findings from this thesis provided insights into future research for more specific non-invasive IBD biomarkers considering the preference of NZ patients with IBD.