Our study showed that the changes in serum LRG between two consecutive colonoscopy tests were significantly correlated with the changes in the endoscopic and histologic activity, when presently available serum biomarkers are not sufficiently effective for monitoring the disease activity. To our knowledge, our results are unique in real-world clinical practice, in the point of view that comparing the changes in the serum LRG/CRP levels and the Fcal/FIT levels with the changes in the endoscopic and histologic scores in the same UC patient.
determined the correlation between serum LRG and the disease activity of UC using single-point analyses
16,17. In addition, the comparison of the biomarkers including LRG with findings of multiple endoscopies has already been reported and discussed in a previous well-conceived prospective report
18. In contrast to the previous studies, our report has the following advantages. First, most of our patients were in remission or mild disease in outpatient settings that enabled validation of usefulness of LRG in real clinical practice with not so large changes in disease activity. Second, all analyzed biomarkers including FIT, which was clinically useful but was not examined in the previous reports, were compared to the endoscopic and histologic findings. The results that the changes in the serum LRG had a strong correlation in with the trend in UC activity, similarly to fecal markers, are meaningful for daily clinical practice.
Based on the above results, we propose the following usage of each biomarker in clinical practice related to UC. In cases with high activity (MES2-3) during the induction period, CRP has been reported to be more strongly correlated with the MES in comparison to fecal markers22,23. The heterogeneity in fecal samples in cases of diarrhea due to excessive disease activity may make measurements inaccurate. In these situations, however, LRG could be useful because CRP are likely to be negative during remission induction despite residual endoscopic activity.
In cases with low disease activity (MES 1), such as those with mild inflammation without clinical symptoms, serum CRP levels are often negative and are not useful9. On the other hand, Fcal and FIT may be significantly correlated with the change from low disease activity to remission (MES 0–1)19,23,24. Based on the present study, the examination of serum LRG may also be useful for these cases. Especially when fecal markers do not show any significant decrease despite appropriate therapeutic intervention, the combined use of the changes in serum LRG with fecal markers may be useful because fecal markers yield false positive results due to the use of non-steroidal anti-inflammatory drugs, the presence of hemorrhoids, inflammatory polyps, colonic diverticulum, the infection with bacteria or viruses, the diurnal variation, or menstruation in women25–30. In determining endoscopic remission (MES 0) and assessing the maintenance of MES 0, fecal markers may be more useful than serum LRG4,5. However, once fecal markers become elevated with or without symptom relapse, the examination of changes in serum LRG may be useful for assessing the changes in disease activity.
The present study was associated with several limitations. First, since this was a single-center study, confirmation by multi-center studies is desirable. Second, the population was biased toward patients with relatively low inflammation (MES 0–1). Similar studies should be conducted that include cases with high inflammation (MES 2–3). Third, the intervals of colonoscopy and biomarker examinations were not fixed and different among individuals. Fourth, all cases with fecal hemoglobin concentrations of < 50 ng/mL were treated as 50 ng/mL in this study. More accurate data may be necessary for patients with hemoglobin concentrations of < 50 ng/mL.
In conclusion, the examination of the changes in serum LRG may be more useful and accurate than serum CRP for assessing the changes of UC disease activity, and shows similar clinical significance to the examination of fecal markers. Measurement of serum LRG can be performed by simple blood collection. Hence, LRG may have utility in the management of the chronic course of UC.