Background: Ustekinumab (UST) was approved in China for moderate-to-severe Crohn’s disease (CD) in 2020. The prevalence rates of tuberculosis and hepatitis B virus (HBV) infection are high in China, and no guideline clearly states that tuberculosis chemoprophylaxis or prophylactic anti-HBV therapy should be prescribed before UST administration. This study aimed to assess the risk of tuberculosis and HBV reactivation in CD patients with latent tuberculosis infection (LTBI) and previous HBV infection receiving UST. Methods: A multicenter retrospective cohort study was carried out at 68 hospitals in China to assess 721 adult CD cases administered UST between May 1, 2020, and December 31, 2021. CD and concurrent LTBI or HBV carrier were included. Hepatitis B serology, T-SPOT.TB, and tuberculin skin tests were performed at baseline. The primary outcome was tuberculosis or HBV reactivation. Results: Patients with CD-concomitant LTBI or who were HBV carriers receiving UST therapy were retrospectively enrolled from 15 hospitals in China. A total of 53 CD with LTBI patients and 17 CD with HBV carrier patients receiving UST were included. Treatment and follow-up durations were 50 ± 20 weeks and 50 ± 15 weeks in the LTBI and HBV carrier groups, respectively. A total of 25 CD patients with LTBI underwent chemoprophylaxis and 28 did not. A total of 11 HBV carriers had antiviral prophylaxis and 6 did not. No patient experienced tuberculosis or HBV reactivation or liver dysfunction during follow-up. Conclusions: UST was safe for treatment of CD because no patient developed tuberculosis, persistent hepatitis, or acute liver failure during therapy, whether with a prophylactic regimen or not, based on our sample size and limited follow-up time.

Although biologics have been revolutionizing the treatment of inflammatory bowel diseases (IBD) over the past decade, a significant number of patients still fail to benefit from these drugs. Overcoming the nonresponse to biologics is one of the top challenges in IBD treatment. In this study, we revealed that hyaluronan (HA), an extracellular matrix (ECM) component in the gut, is associated with nonresponsiveness to infliximab and vedolizumab therapy in patients with IBD. In murine colitis models, inhibition of HA synthase 2–mediated (HAS2-mediated) HA synthesis sensitized the therapeutic response to infliximab. Mechanistically, HA induced the expression of MMP3 in colonic fibroblasts by activating STAT3 signaling, thereby mediating the proteolytic cleavage of multiple IgG1 biologics. Finally, we found that macrophage-derived factors upregulated HAS2 expression in fibroblasts, thereby contributing to infliximab nonresponse. In summary, we identified a pathogenic connection between abnormal ECM remodeling and biologics nonresponse and provided insights for the precise therapy for IBD.

Background/Objectives: Ustekinumab (UST) is an effective and safe drug for treating Crohn’s disease (CD), but data on disease progression after UST treatment is limited. This study aimed to develop a clinical decision support tool (CDST) to identify Chinese patients with CD less likely to experience disease progression during UST treatment. Methods: A multicenter, retrospective observational study was conducted among Chinese patients with CD who started UST treatment between 1 May 2020 and 20 October 2022. Baseline characteristics, defined as the measurements taken closest to, and prior to, the first dose of UST, were collected. Disease progression, defined as CD-related surgery, hospitalization, and complications, was evaluated by week 52 (±4 weeks). Predictors were identified using logistic regression, and a UST-specific CDST (UST-CDST) was developed. The UST-CDST was then internally and externally validated using the area under the receiver operating characteristic curve (AUC). Results: Among 602 enrolled patients, 533 were included in the analysis. Four factors were suggestively associated with disease progression: prior biologics usage, baseline disease severity, baseline C-reactive protein, and baseline hemoglobin. The prediction model demonstrated an AUC of 0.88 in internal validation and 0.66 in external validation. The UST-CDST effectively stratified patients into low-risk or high-risk groups for disease progression within one year. Conclusions: A UST-CDST was developed and validated to identify patients with CD less or more likely to experience disease progression around week 52 under UST therapy. The scoring system promises to facilitate clinical decision-making and personalized treatment.

Background: Chronic enteropathy associated with SLCO2A1 (CEAS) is a rare genetic disorder that is prone to misdiagnosis and characterized by significant challenges in achieving an early diagnosis. Current diagnosis relies on clinical manifestation combined with genetic sequencing. This study aimed to evaluate immunohistochemical (IHC) staining for SLCO2A1 protein deficiency as a diagnostic alternative, in addition to clinical pathological features. Method: Ten patients diagnosed with CEAS between January 2018 and August 2024 were enrolled. Clinicodemographic data, endoscopic findings, and treatment history were collected. Whole-exome sequencing identified SLCO2A1 variants. IHC staining for SLCO2A1 protein was performed from small intestine lesions and accessible GI sites. Results: Complete absence of SLCO2A1 protein expression was demonstrated by IHC in 9/10 patients, with significantly reduced expression in 1/10. This protein deficiency was consistently observed not only in the small intestine but also in the gastric antrum, duodenum, and terminal ileum. Genetic analysis revealed 7 novel SLCO2A1 variants among a total of 11 variants. A median diagnostic delay of 15 years (IQR 6–24) was observed. Ileal involvement and hypoalbuminemia (median albumin 28.02 g/L, IQR 22.1–33.0) were present in all patients. Common symptoms included abdominal pain (70%), melena (60%), and ileus (50%). Conclusions: The diagnosis of CEAS has been time-consuming and challenging. Detection of SLCO2A1 protein deficiency via IHC in either the disease-predominant small bowel or accessible non-lesional upper/lower GI mucosa demonstrates high diagnostic sensitivity for CEAS. This method could provide a practical, cost-effective alternative to genetic sequencing, particularly in resource-limited settings, and has the potential to significantly reduce diagnostic delays for this condition.

Infliximab (IFX) for inflammatory bowel disease (IBD) treatment may increase the risk of hepatitis B virus (HBV) reactivation, particularly in areas with high HBV prevalence such as China. This study aimed to evaluate HBV reactivation/infection, liver dysfunction, vaccination efficacy and strategies in IBD patients undergoing IFX therapy. This retrospective, multicenter study included 4183 IBD patients from 15 hospitals across China, who were divided into six groups according to the HBV status. Demographic features, HBV vaccination status, reactivation/infection rates, and liver dysfunction outcomes were collected, with data collection performed from 2009 to 2022. We found that HBV reactivation rate was notably higher in HBsAg positive group than other groups ( P < 0.05) despite antiviral treatment. Although only 29% of patients were immunized at IFX initiation and almost no patients got vaccinated against HBV during IFX treatment, no patients experienced HBV infection in the susceptible population group. The study underscores a critical need for rigorous HBV screening before IFX initiation. Despite antiviral prophylaxis, the importance of continuous monitoring of HBV DNA is necessary for HBsAg positive patients. HBsAg negative patients, including the susceptible population, had a very low risk of new HBV infection, thus reassuring patients and physicians of the safety of IFX in this cohort.