In this issue of the Journal of Clinical Gastroenterology, Park et al1 report on the long-term outcome of South Korean patients with Crohn’s disease (CD) involving the jejunum. In the retrospective review of 1403 consecutive patients with CD followed up at their medical center, the authors observed jejunal involvement in 14.1% (198/1403) of patients. Jejunal involvement was defined at the time of diagnosis of CD and was made by small bowel follow-through (SBFT) (active and chronic changes in the proximal two fifths of the small bowel) in the majority (96.1%) of patients. Capsule endoscopy, computed tomography (CT) enterography, double balloon endoscopy, and surgery were other modalities used for diagnosis. Of note, 72.3% of CD patients were men with a median age at diagnosis of 23 years, unlike western population studies, which have a slight female preponderance at diagnosis of CD.2,3 In the jejunal group, there were more patients with ileal CD (28.3% vs. 20.6%) and fewer with colonic CD (0% vs. 6.6%) compared with the nonjejunal group (P=0.001). Thus, the jejunal CD group was associated with more extensive small bowel involvement. In addition, more patients in the jejunal group had stricturing (16.7% vs. 9.4%) and penetrating (15.2% vs. 11.2%) disease behavior when compared with nonjejunal CD patients (P<0.001). The 15-year cumulative probability of using thiopurines (98.1% vs. 94.0%; P=0.008) and corticosteroids (94.9% vs. 85.2%; P=0.014) was significantly higher in the jejunal group than in the nonjejunal group, whereas the use of anti-tumor necrosis factor was similar in both groups. Even though the 15-year cumulative probability of the first major surgery was higher in the jejunal CD group, there were no differences in the incidence rates of major surgeries or bowel resections between the 2 groups. In contrast, the incidence rate of strictureplasties [risk ratio (RR), 2.77 (95% confidence interval (CI) , 1.77-4.32, P<0.001)] and all hospitalizations [RR, 1.40 (95% CI, 1.24-1.59; P<0.001)] was significantly higher in the jejunal group than in the nonjejunal group.
A limitation of this study is the potential for misclassification bias. For the ascertainment of jejunal disease, the authors used SBFT as the primary means of determining jejunal involvement in 96.1% of patients, with confirmation by another method in approximately 59.4% of patients. Previous studies have shown that SBFT has a low sensitivity of 65% compared with 82% to 83% for capsule endoscopy and CT enterography.4 By using a low-sensitivity technique, many patients classified as not having jejunal disease may actually have jejunal disease. Hence, gastroenterology societies like the European Crohn’s and Colitis Organisation recommend using CT or magnetic resonance enterography/enteroclysis as the primary means of determining small bowel involvement and reserving SBFT when the above are not available.5 Therefore, when the authors limited their analysis to patients in whom ≥2 diagnostic methods were used or surgical diagnosis was made, there were no differences in the use of thiopurines and corticosteroids, nor in the incidence rates of major surgeries or bowel resections, between the 2 groups. In contrast, the incidence rate of strictureplasties was twice as high in the jejunal group than in the nonjejunal group, with an RR of 2.65 (95% CI, 1.63-4.30; P<0.001). Similarly, the incidence of all hospitalizations (RR, 1.29; 95% CI, 1.13-1.48) and total duration of hospitalizations (RR, 1.32; 95% CI, 1.27-1.36) were significantly higher in the jejunal group than in the nonjejunal group (P<0.001).
In their regression analyses, the authors showed that jejunal involvement was not associated with an increased incidence rate for all major surgeries or bowel resections but was an independent risk factor predicting the increased incidence of strictureplasties, hospitalizations, and the total duration of hospitalizations. The results from patients who underwent 2 tests for diagnosis of jejunal CD were thus similar to their regression analyses. Previous studies have shown that stricturing and penetrating disease behavior along with ileal involvement are associated with the need for surgery.2,6 The more extensive small bowel involvement (more ileal CD patients) and more severe disease behavior seen in the jejunal group could be one of the reasons for the increased stricturplasties and incidence and length of hospitalizations seen in the present study.
Park and colleagues have demonstrated that jejunal CD in Korean patients results in increased hospitalization and strictureplasties but is not an independent predictor of the increased need for major surgery, unlike their western counterparts. The incidence of CD is increasing throughout the world, including in Asia, but there is a dearth of population-based studies from Asia that are devoid of referral center bias.7 As highlighted by this study, phenotypic characteristics that portend worse prognosis may be somewhat dissimilar between western and Asian populations. A single nucleotide polymorphism 3020insC of NOD2 has been correlated with small bowel involvement in French Canadians with CD.8 The decreasing costs of genome sequencing has resulted in newer inflammatory bowel disease (CD and ulcerative colitis) susceptibility loci being identified at a rapid pace, and a recent meta-analysis updated the total to 163 loci.9 With the launch of the Metagenome of Human Intestinal Tract Consortium and Human microbiome project, studies evaluating the role of human gut microbiome in normal subjects and those with disease have also seen an exponential growth.10 A reduction in Faecalibacterium prausnitzii abundance in ileal mucosal samples has been associated with a higher risk for postoperative recurrence of ileal CD.11 Microbiota has been shown to be affected by diet, environment, and host genetics.10 Could the difference in microbiota and the underlying CD susceptibility genes be responsible for the difference in outcomes seen with the same phenotype between western and Korean patients? Future studies, both hospital and population based, from Asian countries that incorporate genetic and gut microbiome profiling in addition to phenotypic characteristics are needed to further elucidate the factors that predict disease behavior and outcomes in patients with CD. Such studies will also lead to a better understanding of the pathogenesis of CD and not just outcomes.
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