Monitoring of leucine-rich alpha-2-glycoprotein and assessment by small bowel capsule endoscopy are prognostic for Crohn's disease patients

Abstract

Background and aim: Endoscopy is important to determine the effectiveness of treatment for Crohn's disease (CD), but searching the entire small intestine is difficult. Thus, we investigated the usefulness of leucine-rich alpha-2 glycoprotein (LRG), a new biomarker for predicting mucosal activity, in evaluating the activity of CD small intestinal lesions. This will further determine whether the results of small bowel capsule endoscopy (SBCE) affect the prognosis of patients with CD.

Methods: A total of 114 patients with CD who underwent SBCE were included. We analyzed the correlation between LRG and Capsule Endoscopy Crohn's Disease Activity Index (CECDAI). The cutoff value of LRG to achieve mucosal healing was calculated using the receiver operating characteristic curve. Then, we compared the presence or absence of intervention and the relapse rate of patients who could not achieve mucosal healing.

Results: The CECDAI correlated with LRG. The calculated LRG value for achieving mucosal healing was ≤11.9. Ninety-one patients were in clinical remission at the time of SBCE. During the follow-up period, 17 patients relapsed. As a result of SBCE, when no treatment intervention was performed in the case of CECDAI ≥3.5, the relapse rate was significantly higher than when CECDAI <3.5 or intervention was performed in the case of CECDAI ≥3.5.

Conclusions: The results reveal that LRG correlates with the activity of the entire small intestine and that SBCE assessment and therapeutic intervention can influence patient prognosis.

Keywords: Crohn's disease; capsule endoscopy Crohn's disease activity index; leucine‐rich alpha‐2 glycoprotein; prognosis; small bowel capsule endoscopy.

Figure 1

Correlation between Lewis score and biomarkers. The relationship between the Lewis score and biomarkers was examined using a correlation chart. All serial time points were put into the chart. The Lewis score ranged from 0 to 4560. No correlation was found between the Lewis score and the WBC count (a). A weak correlation was found between the Lewis score and CRP (b). The Lewis score correlated with LRG (c).

Figure 2

Correlation between CECDAI and biomarkers. The relationship between the CECDAI and biomarkers was examined using a correlation chart. All serial time points were added to the chart. The CECDAI ranged from 0 to 17. No correlation was found between CECDAI and the WBC count (a). A weak correlation was found between CECDAI and CRP (b). The CECDAI correlated with LRG (c).

Figure 3

Determination of LRG values to predict mucosal healing. ROC curve analysis was used to identify optimal cutoff values of LRG with maximum sensitivity and specificity for achieving mucosal healing (Lewis score <135 or CECDAI <3.5). In ROC curve analysis, (a) the calculated LRG value for achieving the “Lewis score” of <135 was ≤11.9, and the AUC was 0.723; sensitivity, 79.5%; specificity, 60.9%; PPV, 55.4%; NPV, 83.0%; and accuracy, 68.0%. (b) The calculated LRG value for achieving CECDAI of <3.5 was also ≤11.9, and the AUC was 0.843; sensitivity, 81.0%; specificity, 80.0%; PPV, 83.9%; NPV, 76.6%; and accuracy, 80.6%.

Figure 4

Relationship between treatment intervention and relapse according to SBCE results. The relationship between treatment intervention after SBCE and relapse was investigated using the Kaplan–Meier method. As a result of SBCE, when no treatment intervention was performed in the case of CECDAI ≧ 3.5 (black), the relapse rate was significantly higher than when intervention was performed in the case of CECDAI ≧ 3.5 or CECDAI <3.5 (P < 0.001).

Figure 5

Images of SBCE in a patient with CD in clinical remission. Multiple small ulcers and erosions are seen in the entire small intestine. This male patient in his 70s had the ileitis type, and he received vedolizumab. His CRP level was within the normal range, and his LRG level was mildly elevated. The CECDAI was 13, and the Lewis score was 3592, but no additional treatment was given at the patient's request. His symptoms flared up 51 days after the SBCE.

Figure 6

Flow of examination with reference to LRG values. When a patient with Crohn's disease does not have active lesions during colonoscopy, if the LRG is ≤12 μg/dL, an aggressive small bowel examination using SBCE or other methods is recommended, and if the activity is high, performing therapeutic intervention is advisable.