Faecal Haemoglobin Estimated by Faecal Immunochemical Tests—An Indicator of Systemic Inflammation with Real Clinical Potential

Abstract

Multimorbidity is the major cause of ill-health and premature death in developed countries. The ability to identify individuals at risk of developing chronic disease, particularly multimorbidity, reliably, and simply, and to identify undiagnosed disorders, is vital to reducing the global burden of disease. This narrative review, the first of recent studies, demonstrates that raised faecal haemoglobin concentration (f-Hb) is associated with increased all-cause and cause-specific mortality and with longer-term conditions including diabetes, hypertension, cardiovascular disease, and psoriasis, and with probable intake of particulate matter. We and others have hypothesized that elevated f-Hb (measured using a faecal immunochemical test) has considerable potential to identify individuals at risk of, or who already have, early stage, undiagnosed chronic disease. If f-Hb does prove to be an effective biomarker for chronic disease and multimorbidity, individuals with detectable f-Hb, but without an obvious source of gastrointestinal blood loss, could benefit from further assessment and early intervention. To test this hypothesis rigorously, longitudinal data-linkage methodology is required linking colorectal cancer screening data, and data on patients presenting with lower gastrointestinal symptoms, with routinely collected health information.

A positive faecal immunochemical test result and its association with the incidence of rheumatoid arthritis, systemic lupus erythematosus, and psoriatic arthritis: an analysis of one-million national colorectal cancer screening programme results

“…It is difficult to clearly explain the FIT (+) but colonoscopy negative group. We inferred that this finding may indicate systemic inflammation, as previously described [9]. Therefore, this study started with the assumption that the FIT (+) group would differ from the FIT (−) group, as they could potentially represent subclinical inflammation.…”

“…Nonetheless, Libby et al [30] and Chen et al [13] have indicated that occult blood in faeces could predict an increase in mortality that is not accounted for CRC among national health-examination recipients, probably representing a generalised inflammatory status. This is also highlighted by a number of studies that have demonstrated an association between positive FIT and the risk of developing chronic disorders, raising a possibility that FIT abnormality, without gross abnormal mucosal lesions, could be an indicator of subjects that are at risk of chronic diseases mirroring heightened inflammation [9]. In the present study, we classified participants undergoing FIT in a national CRC screening programme into FIT (+) and FIT (−) groups and compared the incidence of IMIDs.…”

“…Recent studies have revealed a relationship between the presence of haemoglobin in the faeces and diseases associated with systemic inflammation [9]. Raised faecal haemoglobin concentrations without clear evidence of gastrointestinal bleeding, which can be measured by the faecal immunochemical test (FIT), reflect subclinical inflammation.…”

Alternative diagnoses and demographics associated with a raised quantitative faecal immunochemical test in symptomatic patients

“…It is interesting that this association with deprivation is shared by screening and symptomatic patients. In the review by Barnett et al, 39 they hypothesise that an elevated systemic inflammatory response (SIR) may explain the higher f-Hb concentrations observed in the absence of colorectal pathology, in screener participants with chronic conditions (ischaemic heart disease, cerebrovascular disease, diabetes and hypertension) and on certain medications (PPIs and anticoagulants). Perhaps a heightened SIR is one confounding variable which may link deprivation, co-morbidity and a raised f-Hb in the absence of colorectal pathology.…”

Faecal haemoglobin examinations have come of age, but further maturation seems desirable

“…In contrast, recent studies have shown that detectable f-Hb is associated with increased all-cause and cause-specific mortality, and with longer-term conditions including diabetes, hypertension, cardiovascular disease and psoriasis, and with probable intake of particulate matter. 25 All of these conditions are associated with systemic inflammation. In consequence, the suggestion has been made that elevated f-Hb has considerable potential to identify individuals at risk of, or who already suffer from, early stage, undiagnosed, chronic disease.…”