Background/Aims Inflammatory bowel disease (IBD) is increasing across the globe, more so in populous countries like India. We aimed to study the disease burden and epidemiological trends of IBD in India and look closer into the disease pattern across the country from 1990 to 2019.
Methods The burden of IBD was estimated in India using the data from the Global Burden of Disease estimate for 2019, which is a comprehensive worldwide project. The analysis included various parameters like incidence, prevalence, mortality, disability-adjusted life years, years lived with disability, and years of life lost as age-adjusted rates (per 100,000 population). Using modeling, the prediction was also made for 2050 in India.
Results The age-standardized incidence, prevalence, mortality, and disability rates of IBD in India for 2019 were 2.34, 20.34, 0.40, and 13.04, respectively. These are lower than the global incidence, prevalence, mortality, and disability rates of 4.97, 59.25, 0.54, and 20.15, respectively. The annual rates of change in incidence, prevalence, mortality, and disability rates in India from 1990 to 2019 were 0.05, –0.02, –0.36, and –0.35, respectively. The annual rates of change in incidence and prevalence are higher than the global rate of –0.18 and –0.19, while the annual rates of change in mortality and disability are lower than the global rate of –0.19 and –0.26.
Conclusions The incidence and prevalence of IBD in India are lower compared to the global population but are increasing at a faster rate than the global population.
Background/Aims Sarcopenia is implicated in inflammatory bowel disease (IBD) complications and surgical outcomes. This study aimed to investigate the prevalence and follow-up of sarcopenia in patients with IBD.
Methods Consecutive consenting patients with IBD aged > 18 years were included. Patients with associated sarcopenic diseases were excluded. All had measurements of anthropometry, body mass index (BMI), mid-arm muscle circumference, muscle strength, physical performance, and muscle mass (on computed tomography scan). They were followed up for up to 12 months, and incidence of flares, fractures, and surgery was noted.
Results Of 157 patients screened, 35 refused participation; 5 with associated sarcopenic diseases were excluded. Of 117 patients (median age, 41 years; interquartile range, 18–81 years; 65 men), 73 had ulcerative colitis, 42 Crohn’s disease, and 2 IBD-unclassified. Forty (34.2%) had probable sarcopenia; 47 (40.2%) had sarcopenia (29 ulcerative colitis and 18 Crohn’s disease) including 10 (8.5%) with severe sarcopenia. Ten (21.3%) were in disease remission. Of factors associated with sarcopenia in univariate analysis, only BMI was significant in multivariate analysis. Ninety-nine patients followed up for a median of 7 months (interquartile range, 2–12 months). Freedom from flares was 5.3% in patients with sarcopenia and 46.1% in those without (P= 0.004). Three patients (1 with sarcopenia, 2 without) required surgery.
Conclusions Sarcopenia was present in 40% of patients with IBD; one-fifth of these had severe sarcopenia. One-fifth were in remission. Low BMI correlated with sarcopenia. More patients with sarcopenia had disease flare. Screening for sarcopenia should be considered in patients with IBD.
Background/Aims Crohn’s disease (CD) leads to bowel damage and disability if suboptimally treated. We investigated firstyear treatment decisions and real-world use of biologics in patients with CD in Japan.
Methods In this retrospective observational study (2010–2021) from the JMDC claims database, patients with a new diagnosis of CD (no CD claims record within 12 months before index) who received ≥ 1 pre-defined treatment were grouped by use of biologics and systemic corticosteroids (SCS) within the first year of diagnosis.
Results Of 823 patients included, 470 (57.1%) were prescribed biologics and 353 (42.9%) were not; 77.6% were male, 75.7% had adult-onset CD, and median age was 24 years. Patients prescribed biologics were younger (median: 23 years vs. 28 years) and more had perianal lesions (43.0% vs. 22.9%) than those not prescribed biologics; 64.9% (95% confidence interval, 60.4%–69.2%) received a top-down treatment approach (no SCS before biologics). Factors significantly associated with a top-down treatment approach were male sex, perianal lesions, no use of immunomodulators, and use of anti-tumor necrosis factor therapies. The proportion of patients receiving SCS before biologics (step-up approach) increased after 2018, with a shift from prednisolone to budesonide from 2016. Persistence with first biologics decreased over time, with no differences between biologic types.
Conclusions Use of biologics for treatment of CD within the first year of diagnosis in Japan has remained stable over the past decade. However, there was a shift to a step-up treatment approach, with an increase in use of SCS before biologics over time.
Background/Aims Fatigue is a common symptom in patients with inflammatory bowel disease (IBD). The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale has demonstrated reliability and validity in assessing fatigue in patients with IBD and is used worldwide. This study aimed to examine the current state of fatigue among Japanese patients with IBD using the FACIT-F scale and to compare these findings with data from global studies through a systematic review.
Methods Data from 488 patients with IBD treated at a specialized IBD clinic were analyzed. Patient characteristics, such as sex, age, disease duration, disease activity, FACIT-F scores, and sleep duration, were collected. A literature search identified 8 studies that met our inclusion criteria for an international comparison. A meta-analysis was performed on the Fatigue Subscale (FS) scores of FACIT-F to estimate the pooled mean.
Results The mean FACIT-F (FS) score in this study was 39.9 ± 8.6. Four variables were significantly associated with fatigue: low Emotional Well-Being subscale scores, sleep duration < 6 hours, albumin level below the reference value, and being unmarried. The meta-analysis revealed that the pooled mean score was 40.2 (95% confidence interval, 39.5–40.9), and between-study heterogeneity was moderate (I2 = 41%).
Conclusions The FACIT-F (FS) scores and related factors in Japanese patients with IBD demonstrated a similar trend to those in other countries. These findings can be used to identify patients in need of support and to consider interventions for modifiable factors. This study will help promote international collaborative research.
Background/Aims Radial incision and cutting (RIC) is an alternative dilation method for stenosis of the lower gastrointestinal tract. However, its safety and efficacy for the small intestine requiring balloon-assisted enteroscopy (BAE) remain limited. Therefore, this pilot study aimed to evaluate the safety and efficacy of RIC using BAE.
Methods We included 10 patients with Crohn’s disease and performed 12 sessions of RIC for 10 lesions. The rate of adverse events 1 month after RIC was the primary outcome, whereas short- and long-term prognoses and improvements in subjective symptoms that were evaluated using a visual analog scale were the secondary outcomes.
Results The technical success rate for RIC, defined as scope passage immediately following the procedure, was 100% (12/12). The rates of delayed bleeding and perforation were 0% (0/12). One patient developed restenosis because of the worsening of Crohn’s disease and underwent surgery 2 months after RIC. The cumulative restenosis-, reintervention-, and surgery-free rates at 1 year after RIC were 67.5%, 78.7%, and 90.0%, respectively. Abdominal pain, abdominal bloating, nausea, and difficulties in defecation significantly improved 4 weeks after RIC.
Conclusions RIC for small intestine using BAE has the potential to be safe and effective for relieving symptoms (jRCT identifier jRCTs022200040).
Background/Aims There are few studies that comprehensively report real-world persistence for first-line advanced therapies used to treat inflammatory bowel disease. We aimed to describe persistence of first-line advanced therapies among incident biologic or Janus kinase inhibitor users with inflammatory bowel disease.
Methods Retrospective cohort study using the Japan Medical Data Center database from January 1, 2010, until September 30, 2022. Patients aged ≥15 years with relevant diagnostic and treatment codes were included. All eligible patients were observed until study end (September 30, 2022), death, or disenrollment, whichever occurred first.
Results Among 1,115 patients with Crohn’s disease included in the analysis, 41.4% initiated adalimumab, 37.4% infliximab, 18.1% ustekinumab, and 3.0% vedolizumab. Median age was 31.2–34.8 years, 72.8% to 85.9% were male. Persistence at 12 months was 84.7% for adalimumab, 87.7% for infliximab, 91.3% for ustekinumab, and 53.1% for vedolizumab. Persistence at 24 months was 76.3%, 76.8%, 80.4%, and 28.6%, respectively. Among 1,942 patients with ulcerative colitis, 24.8% initiated adalimumab, 33.6% infliximab, 11.2% golimumab, 17.5% vedolizumab, 5.6% ustekinumab, and 7.3% tofacitinib. Mean age was 38.2–40.4 years, 57.4% to 65.8% were male. Persistence at 12 months was 57.6% for adalimumab, 87.7% for infliximab, 54.9% for golimumab, 69.7% for vedolizumab, and 84.0% for ustekinumab. At month 24, persistence for ustekinumab was 75.0%, versus 42.9%–59.4% for other treatments.
Conclusions Index treatment with ustekinumab resulted in high persistence through 24 months after initiation in patients with Crohn’s disease or ulcerative colitis. Our study provides insights into the real-world usage of advanced treatments for patients with IBD in Japan.
June Hwa Bae, Su Hyun Park, Jung-Bin Park, Ji Eun Baek, Seung Wook Hong, Sung Wook Hwang, Dong-Hoon Yang, Byong Duk Ye, Jeong-Sik Byeon, Seung-Jae Myung, Suk-Kyun Yang, Kyeong Ok Kim, Byung Ik Jang, Mi Rae Lee, Eun Soo Kim, Sang Hyoung Park
Received April 18, 2024 Accepted July 15, 2024 Published online August 29, 2024
Background/Aims Video capsule endoscopy is rarely used to diagnose Crohn’s disease in patients with negative ileocolonoscopy or cross-sectional image findings. We evaluated clinical characteristics and long-term outcomes of these rare cases.
Methods This multicenter study included patients with Crohn’s disease from 3 tertiary hospitals from January 2007 to October 2022. Patients with normal findings on ileocolonoscopy and computed tomography (CT)/magnetic resonance (MR) enterography but had ulcerations at the small bowel detected by video capsule endoscopy were included. The controls were patients with abnormal findings on endoscopy or CT/MR enterography. Controls were case-matched in a ratio of 3:1 for sex, calendar year of diagnosis, and age at diagnosis.
Results Among 3,752 patients, 24 (0.6%) were diagnosed with Crohn’s disease using video capsule endoscopy findings. The disease location (P< 0.001) and behavior at diagnosis (P= 0.013) of the cases significantly differed from that of controls. The perianal fistula modifier (25.0% vs. 33.3%, P= 0.446) did not differ significantly between the 2 groups. Initial disease activity and C-reactive protein and fecal calprotectin levels were significantly lower in cases versus controls. The median Lewis score was 838 (interquartile range, 393–1,803). Over 10 years of follow-up, the cases showed significantly lower cumulative risk of complicated behavior, biologics use, Crohn’s disease-related hospitalization, and surgeries (log-rank test P< 0.05).
Conclusions Patients with Crohn’s disease whose lesions were observed only by video capsule endoscopy were rare, and exhibit different clinical characteristics and a more favorable long-term disease course compared to those who were conventionally diagnosed.
Background/Aims Treatment using tumor necrosis factor-α (TNF-α) inhibitors is one of the risk factors for active tuberculosis (TB) in patients with Crohn’s disease (CD). Biologics, such as ustekinumab (UST) and vedolizumab (VDZ), are less likely to cause opportunistic infections. However, large-scale studies for active TB and biologics other than TNF-α inhibitors are limited. We aimed to investigate the association between biologics and active TB utilizing a Japanese medical claims database.
Methods We analyzed retrospectively the association of the risk of active TB development with treatment using TNF-α inhibitors and other biologics (UST and VDZ) in patients with CD using the Japanese Medical Data Vision (MDV) database between April 2008 and June 2022. The durations of each biologic and biologic-free treatment were calculated for each patient. Univariate and multivariate analyses were performed using the Cox proportional hazards model, with the utilization of biologics considered as time-dependent covariates.
Results We included 28,811 patients with CD in MDV database. Finally, 17,169 patients were analyzed. In total, 7,064 patients were categorized as biologic-naïve, while 10,105 were classified as biologic-experienced. Seventeen patients developed active TB, including 7 on infliximab, 5 on adalimumab, and 5 on no biologics. None of the patients treated with UST and VDZ developed active TB. Multivariate analysis suggested that TNF-α inhibitors were the risk factors for active TB (hazard ratio, 3.66; P= 0.020).
Conclusions TNF-α inhibitors, but not UST or VDZ, are risk factors for active TB in Japanese patients with CD.
Background/Aims Serum leucine-rich alpha-2 glycoprotein (LRG) is a potential biomarker of Crohn’s disease (CD). This study aimed to evaluate the usefulness of LRG in predicting clinical relapse in patients in remission with CD.
Methods This retrospective observational study assessed the relationships among patient-reported outcome (PRO2), LRG, and other blood markers. The influence of LRG on clinical relapse was assessed in patients in remission with CD.
Results Data of 94 patients tested for LRG between January 2021 and May 2023 were collected. LRG level did not correlate with PRO2 score (ρ = 0.06); however, it strongly correlated with C-reactive protein (CRP) level (r=0.79) and serum albumin level (r=–0.70). Among 69 patients in clinical remission, relapse occurred in 22 patients (31.9%). In the context of predicting relapse, LRG showed the highest area under the curve, followed by CRP level, platelet count, and albumin level. Multivariate analysis revealed that only LRG (P= 0.02) was an independent factor for predicting clinical remission. The cumulative non-relapse rate was significantly higher in patients with LRG < 13.8 μg/mL than in patients in remission with LRG ≥ 13.8 μg/mL and normal CRP level (P= 0.002) or normal albumin level (P= 0.001). Cumulative non-relapse rate was also higher in patients with LRG < 13.8 μg/mL compared to those with LRG ≥ 13.8 μg/mL in patients with L3 or B2+B3 of Montreal calcification.
Conclusions LRG is useful in predicting clinical relapse in patients with CD during biological remission. LRG is a useful biomarker for predicting prognosis, even in patients with intestinal stenosis, or previous/present fistulas.
Crohn’s disease (CD) is a chronic, fluctuating inflammatory condition that primarily affects the gastrointestinal tract. Although the incidence of CD in Taiwan is lower than that in Western countries, the severity of CD presentation appears to be similar between Asia and the West. This observation indicates the urgency for devising revised guidelines tailored to the unique reimbursement system, and patient requirements in Taiwan. The core objectives of these updated guidelines include the updated treatment choices and the integration of the treat-to-target strategy into CD management, promoting the achievement of deep remission to mitigate complications and enhance the overall quality of life. Given the diversity in disease prevalence, severity, insurance policies, and access to medical treatments in Taiwan, a customized approach is imperative for formulating these guidelines. Such tailored strategies ensure that international standards are not only adapted but also optimized to local contexts. Since the inception of its initial guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease (TSIBD) has acknowledged the importance of continuous revisions for incorporating new therapeutic options and evolving disease management practices. The latest update leverages international standards and recent research findings focused on practical implementation within the Taiwanese healthcare system.
Background/Aims Crohn’s disease (CD) has a progressive nature and commonly perianal involvement. The aim of this study is to assess the prevalence, surgical treatment, and outcome of perianal fistulizing CD with associated risk factors in a large Chinese cohort.
Methods Hospitalized patients diagnosed with CD in our center were consecutively enrolled between January 2000 and December 2018. Transition of disease behavior was classified according to the presence or absence of penetrating behavior (B3 in the Montreal classification) at diagnosis and at a median follow-up of 102 months.
Results A total of 504 patients were included, of whom 207 (41.1%) were classified as B3 and 348 (69.0%) as L2/3 at follow-up. Transition of behavior to B3 was observed in 86 patients (17.1%). The incidence of perianal fistulizing lesions was 10.9% at 10 years with a final prevalence of 27.0% (n = 136) at the end of follow-up. Multivariate Cox regression identified independent risks of perianal fistulizing lesions for persistent B3 (hazard ratio, 4.72; 95% confidence interval, 1.91–11.66) and behavior transition of progressed to B3 (hazard ratio, 9.90; 95% confidence interval, 4.60–21.33). Perianal surgical treatments were performed in 104 patients (20.6%). Thirty-six cases (7.1%) were refractory, and it is independently associated with behavior of persistent B3 (P= 0.011).
Conclusions Perianal fistulizing lesions occurred frequently in Chinese CD patients. Its incidence and refractory outcome were closely associated with the penetrating CD behavior. An additional risk of perianal fistulizing lesions was indicated for CD patients with behavior of progressing to B3, suggesting further attention.
Nonalcoholic fatty liver disease (NAFLD) has been shown to be linked to inflammatory bowel disease (IBD) due to established risk factors such as obesity, age, and type 2 diabetes in numerous studies. However, alternative research suggests that factors related to IBD, such as disease activity, duration, and drug-induced toxicity, can contribute to NAFLD. Recent research findings suggest IBD relapses are correlated with dysbiosis, mucosal damage, and an increase in cytokines. In contrast, remission periods are characterized by reduced metabolic risk factors. There is a dichotomy evident in the associations between NAFLD and IBD during relapses and remissions. This warrants a nuanced understanding of the diverse influences on disease manifestation and progression. It is possible to provide a holistic approach to care for patients with IBD by emphasizing the interdependence between metabolic and inflammatory disorders.
Background/Aims Small bowel capsule endoscopy (SBCE) is an evaluation method for small bowel (SB) lesions in Crohn’s disease (CD). However, the relationship between SBCE findings and the serological biomarker leucine-rich alpha-2 glycoprotein (LRG) remains unclear. We aimed to establish appropriate cutoff values of LRG to predict the presence of SB lesions in CD through SBCE.
Methods Patients with CD with SB lesions who had undergone SBCE and LRG measurements 1 month before and after the SBCE were included. The LRG values for ulcers ≥0.5 cm and other inflammatory lesions noted in SBCE were determined using the Youden Index, and the sensitivity and specificity were calculated. Additionally, the correlation between the SBCE scores (CD Activity in Capsule Endoscopy) and LRG values was evaluated.
Results Forty patients without active colorectal lesions were included in the study. When the cutoff value of LRG for SB ulcers ≥ 0.5 cm was set at 14 μg/mL, the sensitivity was 92.3%, specificity was 81.5%, positive predictive value (PPV) was 70.6%, and negative predictive value (NPV) was 95.7%. In contrast, an LRG cutoff value of 12 μg/mL without inflammatory findings had a sensitivity of 91.7%, specificity of 82.1%, PPV of 68.8%, and NPV of 95.8%. CD Activity in Capsule Endoscopy correlated well with LRG values (Spearman’s rank correlation coefficient ρ = 0.681, P< 0.001).
Conclusions An LRG cutoff value of 14 μg/mL may be useful in predicting the presence of SB ulcers ≥ 0.5 cm, and an LRG cutoff value of 12 μg/mL may be useful in predicting the absence of SB inflammatory findings.
Background/Aims Nonalcoholic fatty liver disease (NAFLD) is a common disease with severe inflammatory processes associated with numerous gastrointestinal diseases, such as inflammatory bowel disease (IBD). Therefore, we investigated the relationship between NAFLD and IBD and the possible risk factors associated with the diagnosis of IBD.
Methods This longitudinal nationwide cohort study investigated the risk of IBD in patients with NAFLD alone. General characteristics, comorbidities, and incidence of IBD were also compared.
Results Patients diagnosed with NAFLD had a significant risk of developing IBD compared to control individuals, who were associated with a 2.245-fold risk of the diagnosis of IBD and a 2.260- and 2.231-fold of increased diagnosis of ulcerative colitis and Crohn’s disease, respectively (P< 0.001). The cumulative risk of IBD increased annually during the follow-up of patients with NAFLD (P< 0.001).
Conclusions Our results emphasize that NAFLD significantly impacts its incidence in patients with NAFLD. If patients with NAFLD present with risk factors, such as diabetes mellitus and dyslipidemia, these conditions should be properly treated with regular follow-ups. Furthermore, we believe that these causes may be associated with the second peak of IBD.
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Background/Aims Transabdominal ultrasonography (US) helps evaluate Crohn’s disease (CD) activity. We investigated whether the US could predict subsequent adverse outcomes for patients with CD in clinical remission.
Methods This single-center retrospective study included patients with CD in clinical remission who underwent US between April 2011 and April 2021, focusing on the predictability of subsequent adverse outcomes within 5 years. We used the US-CD, which was calculated using multiple US findings. Predictive variables were assessed using Cox proportional hazards regression analysis, and the predictive value was evaluated using receiver operating characteristic curves.
Results Seventy-three patients were included. During a median follow-up of 1,441 days (range, 41–1,825 days), 16.4% (12/73) experienced clinical relapse, 9.6% (7/73) required endoscopic balloon dilation (EBD), 58.9% (43/73) required enhanced treatment, and 20.5% (15/73) underwent surgery. In the multivariate analysis, US-CD was significantly associated with clinical relapse (P= 0.038) and the need for enhanced treatment (P= 0.005). The area under the receiver operating characteristic curve for predicting clinical relapse and the need for EBD was 0.77 and 0.81, respectively, with US-CD (cutoff value = 11), and that for requiring enhanced treatment was 0.74 with US-CD (cutoff value = 6). Patients with US-CD ≥ 11 demonstrated a significantly higher occurrence of clinical relapse (P= 0.001) and EBD (P= 0.002) within 5 years. Patients with US-CD ≥ 6 experienced a significantly higher likelihood of requiring enhanced treatment (P< 0.001) within 5 years.
Conclusions High US-CD is associated with subsequent adverse outcomes in patients with CD.
Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, is a nonspecific chronic inflammation of the gastrointestinal tract. Despite recent advances in therapeutics and newer management strategies, IBD largely remains untreatable. Helminth therapy is a promising alternative therapeutic for IBD that has gained some attention in the last two decades. Helminths have immunomodulatory effects and can alter the gut microbiota. The immunomodulatory effects include a strong Th2 immune response, T-regulatory cell response, and the production of regulatory cytokines. Although concrete evidence regarding the efficacy of helminth therapy in IBD is lacking, clinical studies and studies done in animal models have shown some promise. Most clinical studies have shown that helminth therapy is safe and easily tolerable. Extensive work has been done on the whipworm Trichuris, but other helminths, including Schistosoma, Trichinella, Heligmosomoides, and Ancylostoma, have also been explored for pre-clinical and animal studies. This review article summarizes the potential of helminth therapy as an alternative therapeutic or an adjuvant to the existing therapeutic procedures for IBD treatment.
Background/Aims Assessment of quality of magnetic resonance enterography (MRE) in small bowel Crohn’s disease (CD) activity evaluation has received little attention. We assessed the impact of bowel distention and motion artifact on MRE activity indices in ileal CD.
Methods A cohort of patients who underwent contemporaneous MRE and colonoscopy for ileal CD assessment between 2014 and 2021 at 2 centers were audited. An abdominal radiologist blinded to clinical data reviewed each MRE, graded bowel distention and motion artifact upon a pre-specified 3-point scale and calculated the original magnetic resonance index of activity (MaRIA) and simplified MaRIA (sMaRIA), London index and CD MRE index (CDMI). Ileal endoscopic activity was graded via the Simplified Endoscopy Score for CD (SES-CD). The performance of MRE indices in discriminating active disease (SES-CD ≥3) stratified by MRE quality was measured by receiver operator characteristic analyses.
Results One hundred and thirty-seven patients had MRE and colonoscopy within a median of 16 days (range, 0–30 days) with 63 (46%) exhibiting active disease (SES-CD ≥3). Forty-four MREs (32%) were deemed low quality due to motion artifact and/or moderate to poor distention. Low-quality MREs demonstrated reduced discriminative performance between ileal SES-CD ≥3 and MRE indices (MaRIA 0.838 vs. 0.634, sMaRIA 0.834 vs. 0.527, CDMI 0.850 vs. 0.595, London 0.748 vs. 0.511, P<0.05 for all). Individually the presence of any motion artifact markedly impacted the discriminative performance (e.g., sMaRIA area under the curve 0.544 vs. 0.814, P<0.05).
Conclusions Image quality parameters can significantly impact MRE disease activity interpretation. Quality metrics should be reported, enabling cautious interpretation in lower-quality studies.
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Background/Aims Endoscopic activity confirmed by enteroscopy is associated with poor clinical outcome in Crohn’s disease (CD). We investigated which of the existing biomarkers best reflects endoscopic activity in CD patients including the small bowel, and whether their combined use can improve accuracy.
Methods One hundred and four consecutive patients with ileal and ileocolonic type CD who underwent balloon-assisted enteroscopy (BAE) from October 2021 to August 2022 were enrolled, with clinical and laboratory data prospectively collected and analyzed.
Results Hemoglobin, platelet count, C-reactive protein, leucine-rich alpha-2 glycoprotein (LRG), fecal calprotectin, and fecal hemoglobin all showed significant difference in those with ulcers found on BAE. LRG and fecal calprotectin showed the highest areas under the curve (0.841 and 0.853) for detecting ulcers. LRG showed a sensitivity of 78% and specificity of 80% at a cutoff value of 13 μg/mL, whereas fecal calprotectin showed a sensitivity of 91% and specificity of 67% at a cutoff value of 151 μg/g. Dual positivity for LRG and fecal calprotectin, as well as LRG and fecal hemoglobin, both predicted ulcers with an improved specificity of 92% and 100%. A positive LRG or fecal calprotectin/hemoglobin showed an improved sensitivity of 96% and 91%. Positivity for LRG and either of the fecal biomarkers was associated with increased risk of hospitalization, surgery, and relapse.
Conclusions The biomarkers LRG, fecal calprotectin, and fecal hemoglobin can serve as noninvasive and accurate tools for assessing activity in CD patients confirmed by BAE, especially when used in combination.
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Inflammatory bowel disease (IBD) is a multifactorial disease, which is thought to be an interplay between genetic, environment, microbiota, and immune-mediated factors. Dysbiosis in the gut microbial composition, caused by antibiotics and diet, is closely related to the initiation and progression of IBD. Differences in gut microbiota composition between IBD patients and healthy individuals have been found, with reduced biodiversity of commensal microbes and colonization of opportunistic microbes in IBD patients. Gut microbiota can, therefore, potentially be used for diagnosing and prognosticating IBD, and predicting its treatment response. Currently, there are no curative therapies for IBD. Microbiota-based interventions, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, have been recognized as promising therapeutic strategies. Clinical studies and studies done in animal models have provided sufficient evidence that microbiota-based interventions may improve inflammation, the remission rate, and microscopic aspects of IBD. Further studies are required to better understand the mechanisms of action of such interventions. This will help in enhancing their effectiveness and developing personalized therapies. The present review summarizes the relationship between gut microbiota and IBD immunopathogenesis. It also discusses the use of gut microbiota as a noninvasive biomarker and potential therapeutic option.
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Background/Aims Evidence on predictors of primary nonresponse (PNR), and secondary loss of response (SLR) to anti-tumor necrosis factor (anti-TNF) agents in inflammatory bowel disease is scarce from Asia. We evaluated clinical/biochemical/molecular markers of PNR/SLR in ulcerative colitis (UC) and Crohn’s disease (CD).
Methods Inflammatory bowel disease patients treated with anti-TNF agents (January 2005–October 2020) were ambispectively included. Data concerning clinical and biochemical predictors was retrieved from a prospectively maintained database. Immunohistochemistry for expression of oncostatin M (OSM), OSM receptor (OSM-R), and interleukin-7 receptor (IL-7R) were done on pre anti-TNF initiation mucosal biopsies.
Results One-hundred eighty-six patients (118 CD, 68 UC: mean age, 34.1±13.7 years; median disease duration at anti-TNF initiation, 60 months; interquartile range, 28–100.5 months) were included. PNR was seen in 17% and 26.5% and SLR in 47% and 28% CD and UC patients, respectively. In CD, predictors of PNR were low albumin (P<0.001), postoperative recurrence (P=0.001) and high IL-7R expression (P<0.027) on univariate; and low albumin alone (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.03–0.28; P<0.001) on multivariate analysis respectively. Low albumin (HR, 0.31; 95% CI, 0.15–0.62; P=0.001) also predicted SLR. In UC, predictors of PNR were low albumin (P<0.001), and high C-reactive protein (P<0.001), OSM (P<0.04) and OSM-R (P=0.07) stromal expression on univariate; and low albumin alone (HR, 0.11; 95% CI, 0.03–0.39; P=0.001) on multivariate analysis respectively.
Conclusions Low serum albumin at baseline significantly predicted PNR in UC and PNR/SLR in CD patients. Mucosal markers of PNR were high stromal OSM/OSM-R in UC and high IL-7R in CD patients.
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Background/Aims The study objective is to investigate the ultrasound features that allow suspecting the presence of submucosal fat deposition, called the fat halo sign (FHS), in the intestinal wall of patients with Crohn’s disease.
Methods Computed tomography (CT) examinations over a period of 10 years were reviewed for the presence of the FHS in the bowel wall. A measurement of less than –10 Hounsfield units was regarded as indicative of fat. We included only patients who had undergone ultrasound examinations 3 months before or after CT. The study cohort group comprised 68 patients. Wall and submucosal thickness were measured on longitudinal ultrasound sections. A receiver operating characteristic curve was constructed to determine the best cutoff of ultrasound submucosal wall thickness value for predicting FHS in the bowel wall determined on CT.
Results The FHS was present in 22 patients (31%) on CT. There were significant differences between submucosal thickness of patients with FHS and patients without FHS (4.19 mm vs. 2.41 mm). From the receiver operating characteristic curve, a threshold value of 3.1 mm of submucosal thickness had the best sensitivity and specificity to suspect FHS (95.5% and 89.1%, respectively; area under the curve, 0.962), with an odds ratio of 172. All of 16 patients with a submucosal thickness >3.9 mm had FHS.
Conclusions FHS in patients with Crohn’s disease can be suspected on ultrasound in cases with marked thickening of the submucosa layer. In these cases, the activity of the disease should be measured by other parameters such as the color Doppler.
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Role of Intestinal Ultrasound for IBD Care: A Practical Approach Joerg C. Hoffmann, Tobias Ungewitter Diagnostics.2024; 14(15): 1639. CrossRef
Background/Aims The data on the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in patients with inflammatory bowel disease (IBD) are conflicting. The present systematic review was thus conducted to study the prevalence of HBV and HCV markers in patients with IBD.
Methods A comprehensive literature search of 3 databases was conducted from 2000 to April 2022 for studies evaluating the prevalence of HBV or HCV in patients with IBD. Pooled prevalence rates across studies were expressed with summative statistics.
Results A total of 34 studies were included in the final analysis. The pooled prevalence of hepatitis B surface antigen (HBsAg) and hepatitis B core antibodies were 3.3% and 14.2%, respectively. In HBsAg positive IBD patients, hepatitis B e antigen positivity and detectable HBV DNA were seen in 15.3% and 61.0% of patients, respectively. Only 35.6% of the IBD patients had effective HBV vaccination. The pooled prevalence of anti-HCV and detectable HCV RNA were 1.8% and 0.8%, respectively. The pooled prevalence of markers of HBV infection was higher in Asian studies, while the prevalence of markers of HCV infection was higher in European studies. The prevalence of viral hepatitis markers was similar between IBD patients and the general population and that between ulcerative colitis and Crohn’s disease.
Conclusions The prevalence of markers of viral hepatitis remains same as the general population with significant regional variations, although the quality of evidence remains low due to publication bias. Only a small proportion of IBD patients had an effective HBV vaccination, requiring improvement in screening and vaccination practices.
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Background/Aims The inflammatory bowel disease (IBD)-disk is a validated, visual, 10-item, self-administered questionnaire used to evaluate IBD-related disability. The present study aimed to evaluate IBD-disk in assessment of IBD daily life burden and its relation with disease activity. Methods: A cross-sectional study was conducted between June 2021 and December 2021. Patients with IBD were asked to complete the IBD-disk and a visual analogue scale of IBD daily-life burden (scored from 0–10, score >5 indicative of high burden). The internal consistency of IBD-disk, correlation with IBD daily life burden and disease activity (assessed by partial Mayo score and Harvey Bradshaw Index in patients with ulcerative colitis [UC] and Crohn’s disease [CD], respectively) and diagnostic performance of IBD-disk to detect high burden were analyzed. Results: Out of the 546 patients (mean age 40.33±13.74 years, 282 [51.6%] males) who completed the IBD-disk, 464 (84.98%) had UC and the remaining (n=82, 15.02%) had CD. A total of 311 patients (291 UC and 20 CD; 56.95%) had active disease. The mean IBD-disk total score and IBD daily life burden were 18.39±15.23 and 2.45±2.02, respectively. The IBD-disk total score correlated strongly with the IBD daily life burden (ρ=0.94, P<0.001), moderately with partial Mayo score (ρ=0.50) and weakly with Harvey Bradshaw Index (ρ=0.34). The IBD-disk total score >30 predicted high IBD daily-life burden. Conclusions: The IBD-disk accurately predicts the daily life burden and parallels disease activity in patients with IBD and can be applied in clinical practice. (Intest Res, Published online)
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Seong-Joon Koh, Sung Noh Hong, Soo-Kyung Park, Byong Duk Ye, Kyeong Ok Kim, Jeong Eun Shin, Yong Sik Yoon, Hong Sub Lee, Sung Hoon Jung, Miyoung Choi, Soo-Young Na, Chang Hwan Choi, Joo Sung Kim, on behalf of the IBD Research Group of the Korean Association for the Study of Intestinal Diseases
Intest Res 2023;21(1):43-60. Published online October 18, 2022
Crohn’s disease (CD) is a relapsing and progressive condition characterized by diarrhea, abdominal pain, weight loss, and hematochezia that results in serious complications such as perforations, fistulas, and abscesses. Various medications, interventions, and surgical treatments have been used to treat CD. The Korean guidelines for CD management were distributed in 2012 and revised in 2017 by the Inflammatory Bowel Disease (IBD) Research Group of the Korean Association for the Study of Intestinal Diseases. Substantial progress in mucosal immunologic research has elucidated the pathophysiology of IBD, leading to development of biological agents for treatment of CD. The first developed biologic agent, tumor necrosis factor-α agents, were shown to be efficacious in CD, heralding a new era in management of CD. Subsequently, vedolizumab, a monoclonal antibody against integrin α4β7, and ustekinumab, a human monoclonal antibody that inhibits the common p40 subunit of interleukin-12 and interleukin-23, were both approved for clinical use and are efficacious and safe for both induction and maintenance of remission in moderate-to-severe CD patients. Moreover, a recent study showed the non-inferiority of CT-P13, an infliximab biosimilar, compared with infliximab in CD patients. The third Korean guidelines for CD management provide updated information regarding treatment of moderate-to-severe CD patients with biologic agents.
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Yu Kyung Jun, Hyuk Yoon, Seong-Joon Koh, A Hyeon Kim, Kwang Woo Kim, Jun Won Park, Hyun Jung Lee, Hyoun Woo Kang, Jong Pil Im, Young Soo Park, Joo Sung Kim, on behalf of Seoul National University Inflammatory Bowel Disease Research Network (SIRN)
Intest Res 2023;21(2):244-251. Published online August 8, 2022
Background/Aims Patients with inflammatory bowel disease (IBD) are diagnosed with ankylosing spondylitis (AS) often. However, the disease course of patients with both IBD and AS is not well understood. This study aims to evaluate the effect of concomitant AS on IBD outcomes.
Methods Among the 4,722 patients with IBD who were treated in 3 academic hospitals from 2004 to 2021, 55 were also diagnosed with AS (IBD-AS group). Based on patients’ electronic medical records, the outcomes of IBD in IBD-AS group and IBD group without AS (IBD-only group) were appraised.
Results The proportion of patients treated with biologics or small molecule therapies was significantly higher in IBD-AS group than the proportion in IBD-only group (27.3% vs. 12.7%, P= 0.036). Patients with both ulcerative colitis and AS had a significantly higher risk of biologics or small molecule therapies than patients with only ulcerative colitis (P< 0.001). For univariable logistic regression, biologics or small molecule therapies were associated with concomitant AS (odds ratio, 4.099; 95% confidence interval, 1.863–9.021; P< 0.001) and Crohn’s disease (odds ratio, 3.552; 95% confidence interval, 1.590–7.934; P= 0.002).
Conclusions Concomitant AS is associated with the high possibility of biologics or small molecule therapies for IBD. IBD patients who also had AS may need more careful examination and active treatment to alleviate the severity of IBD.
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After oncologic resection, histological grading and staging of the tumor give important prognostic information about the future risk of recurrence and hence influence the subsequent management plan. Several studies and their meta-analysis have shown that various histological features (e.g., microscopic positive resection margins, plexitis, granuloma, mesenteric inflammatory activity) can predict postoperative clinical/endoscopic/surgical recurrence after resection in Crohn’s disease (CD). Inclusion of mesentery in surgical resection specimens has been shown to reduce surgical recurrence after ileocolonic resection in CD. However, there is no uniform histopathological staging system for risk stratification in postoperative CD to systematically predict postoperative recurrence. This is because the prediction to date is based on clinical characteristics (smoking status, disease phenotype, surgical history). Histopathological predictors are still not adopted in routine clinical practice due to the lack of a uniform staging system, heterogeneity of published studies and lack of standardized definition of histological features. In this article, we attempted to incorporate all such histological features in a single histological staging system CNM (Crohn’s primary site [resection margin positivity, plexitis, granuloma, depth of infiltration], nodes [presence of granuloma], mesentery [involved or not]) in surgical resection specimen in CD. The proposed CNM classification would help to enable systematic reporting, design future clinical trials, stratify postoperative recurrence risk and choose appropriate postoperative prophylaxis.
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Endoscopic Assessment of Postoperative Recurrence in Crohn's Disease Partha Pal, D. Nageshwar Reddy, Guduru Venkat Rao Gastrointestinal Endoscopy Clinics of North America.2025; 35(1): 121. CrossRef
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Background/Aims Abdominal aortic calcium (AAC) deposition has been suggested as a marker of early atherosclerosis. There is no published data on the evaluation of AAC in inflammatory bowel disease (IBD).
Methods AAC was quantified by computed tomography or enterography scans performed in 98 IBD patients and 1:1 age and sex matched controls. AAC deposition was correlated with IBD characteristics, disease activity or severity parameters, laboratory tests and cardiovascular disease (CVD) risk factors.
Results Moderate-severe grade of AAC was found in 35.7% of IBD patients compared to 30.6% of controls (P= 0.544). IBD with CVD and ulcerative colitis patients had significantly higher rates of more severe atherosclerotic lesions (P= 0.001 and P= 0.01, respectively). AAC deposition was similarly distributed in age groups ( < 45, 45–64, and ≥ 65 years) among patients and controls. Multivariate analysis after excluding CVD risk confounders for non-CVD patients found extensive disease (P= 0.019) and lifetime steroids (P= 0.04) as independent risk factors for AAC. Anti-tumor necrosis factor α (TNF-α) use was negatively associated with AAC deposition in non-CVD IBD patients (odds ratio, 0.023; 95% confidence interval, 0.001–0.594; P= 0.023).
Conclusions More than one-third of IBD patients have moderate to severe AAC. Better control of inflammation with anti-TNF-α agents seems to protect IBD patients from ACC deposition and subsequent atherosclerosis.
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Background/Aims Inflammatory bowel disease (IBD) is increasingly being recognized in elderly patients. Data on clinical spectrum of elderly-onset IBD patients is lacking from India.
Methods A cross-sectional retrospective analysis of a prospectively maintained database of patients diagnosed with IBD was conducted at 2 centers in India. The clinical spectrum of elderly-onset IBD including demographic profile (age and sex), clinical presentation, disease characteristics (disease behavior and severity, extent of disease), and treatment were recorded and compared with adult-onset IBD.
Results During the study period, 3,922 (3,172 ulcerative colitis [UC] and 750 Crohn’s disease [CD]) patients with IBD were recorded in the database. A total of 186 patients (4.74%; 116 males [62.36%]) had elderly-onset IBD (69.35% UC and 30.64% CD). Diarrhea, blood in stools, nocturnal frequency and pain abdomen were the commonest presentations for UC, whereas pain abdomen, weight loss and diarrhea were the most frequent symptoms in CD. For both elderly onset UC and CD, majority of the patients had moderately severe disease. Left-sided colitis was the commonest disease location in UC. Isolated ileal disease and inflammatory behavior were the most common disease location and behavior, respectively in CD. 5-Aminosalicylates were the commonest prescribed drug for both elderly onset UC and CD. Thiopurines and biologics were used infrequently. Prevalence of colorectal cancer was higher in elderly onset IBD.
Conclusions Elderly onset IBD is not uncommon in India. Both the elderly onset UC and CD were milder, with no significant differences in disease characteristics (disease extent, location and behavior) when compared to adult-onset IBD. Colorectal cancer was more common in elderly onset IBD.
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Kyunghwan Oh, Hee Seung Hong, Nam Seok Ham, Jungbok Lee, Sang Hyoung Park, Suk-Kyun Yang, Hyuk Yoon, You Sun Kim, Chang Hwan Choi, Byong Duk Ye, on behalf of the Korean Association for the Study of Intestinal Diseases
Intest Res 2023;21(1):137-147. Published online July 12, 2022
Background/Aims We investigated the real-world effectiveness and safety of ustekinumab (UST) as induction treatment for Koreans with Crohn’s disease (CD).
Methods CD patients who started UST were prospectively enrolled from 4 hospitals in Korea. All enrolled patients received intravenous UST infusion at week 0 and subcutaneous UST injection at week 8. Clinical outcomes were assessed using Crohn’s Disease Activity Index (CDAI) scores at weeks 8 and 20 among patients with active disease (CDAI ≥150) at baseline. Clinical remission was defined as a CDAI <150, and clinical response was defined as a reduction in CDAI ≥70 points from baseline. Safety and factors associated with clinical remission at week 20 were also analyzed.
Results Sixty-five patients were enrolled between January 2019 and December 2020. Among 49 patients with active disease at baseline (CDAI ≥150), clinical remission and clinical response at week 8 were achieved in 26 (53.1%) and 30 (61.2%) patients, respectively. At week 20, 27 (55.1%) and 35 (71.4%) patients achieved clinical remission and clinical response, respectively. Twenty-seven patients (41.5%) experienced adverse events, with serious adverse events in 3 patients (4.6%). One patient (1.5%) stopped UST therapy due to poor response. Underweight (body mass index <18.5 kg/m2) (odds ratio [OR], 0.085; 95% confidence interval [CI], 0.014–0.498; P=0.006) and elevated C-reactive protein at baseline (OR, 0.133; 95% CI, 0.022–0.823; P=0.030) were inversely associated with clinical remission at week 20.
Conclusions UST was effective and well-tolerated as induction therapy for Korean patients with CD.
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Corrigendum: Real-world effectiveness and safety of ustekinumab induction therapy for Korean patients with Crohn’s disease: a KASID prospective multicenter study Kyunghwan Oh, Hee Seung Hong, Nam Seok Ham, Jungbok Lee, Sang Hyoung Park, Suk-Kyun Yang, Hyuk Yoon, You Sun Kim, Chang Hwan Choi, Byong Duk Ye Intestinal Research.2023; 21(2): 273. CrossRef