Clinical Gastroenterology and Hepatology最新文献

Background and aims: Anti-integrin αvβ6 autoantibodies (anti-αvβ6) are found in more than 50% of individuals with ulcerative colitis (UC). We aimed to determine the prevalence of anti-αvβ6 in patients with primary sclerosing cholangitis (PSC) and their association with liver disease severity.

Methods: Four cohorts of pre-liver transplant PSC patients were recruited. Patients with inflammatory bowel disease (IBD) and healthy controls (HC) served as comparators. Total IgG and anti-αvβ6 levels were measured using enzyme-linked immunosorbent assay (ELISA). Olink® inflammation panel was run on a subset of samples. Multivariable linear regression analysis was performed to assess the association between anti-αvβ6 and indices of liver disease severity.

Results: A total of 137 PSC patients (including 76 with PSC-UC, 33 with PSC-Crohn's disease (CD) and 28 with PSC alone) and 160 controls (including 91 with IBD and 69 HC) were enrolled. Anti-αvβ6 levels were significantly higher in PSC-UC and PSC-CD compared to PSC alone (p<0.0001 and 0.003) and HC (p<0.0001 and p<0.0001). However, anti-αvβ6 levels in PSC alone were not increased compared to HC. In patients with PSC-IBD, anti-αvβ6 levels correlated with markers of liver disease severity including alkaline phosphatase level (r=0.32, p=0.004), the revised Mayo PSC risk score (r=0.25, p=0.02) and liver stiffness measurement (r=0.43, p=0.008) after adjusting for age, gender, race/ethnicity and IBD subtype. Additionally, anti-αvβ6 levels were associated with markers of systemic inflammation and tissue remodeling.

Conclusion: Anti-αvβ6 autoantibodies identify a subset of PSC patients with concomitant IBD.

Background and aims: Risankizumab is a selective IL23 inhibitor approved for the treatment of Crohn's disease (CD). We report a large long-term real-world experience with risankizumab in CD.

Methods: We performed a prospective monitoring of clinical outcomes in patients in our center who started treatment with risankizumab. Patients with active luminal disease who had at least 12 weeks of follow-up were included in the effectiveness analysis. Harvey-Bradshaw Index (HBI) as well as C-reactive protein (CRP) and fecal calprotectin (FCP) were used to monitor disease activity. Primary outcomes were clinical remission and steroid-free clinical remission rates at weeks 12, 26, and 52. Univariate analysis followed by a multivariate analysis using a logistic regression model was performed to identify predictors of steroid-free clinical remission at one year. All patients who started treatment with risankizumab for any indication were included in the safety analysis.

Results: 134 patients were included in the effectiveness analysis. 70 (52%) were ustekinumab-experienced. Clinical remission rates were 69%, 64%, and 54% at weeks 12, 26, and 52, respectively. Steroid-free clinical remission rates at 12, 26, and 52 weeks were 58%, 58%, and 50% respectively. Remission rates in ustekinumab-experienced patients were not statistically lower compared to naïve patients, and in a multivariate analysis, prior ustekinumab treatment was not associated with lower odds of achieving steroid-free clinical remission at one year. Adverse effects were assessed in 243 patients and were consistent with previous literature.

Conclusions: This large real-world experience with risankizumab with long-term follow-up demonstrates effectiveness and safety in patients with CD; there was comparable effectiveness in ustekinumab-naïve and ustekinumab-experienced patients.

Background and aims: Patient-reported outcomes (PROs) are pivotal in assessing treatment efficacy and estimating the burden of inflammatory bowel diseases (IBD). We investigated PROs at the time of IBD diagnosis.

Methods: The Short Inflammatory Bowel Disease Questionnaire (SIBDQ), IBD-Disability Index (IBD-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and disease activity-related PROs were assessed in the Copenhagen IBD Inception Cohort, a prospective, population-based cohort of patients newly diagnosed with IBD between May 2021 and May 2023.

Results: A total of 203 UC and 116 CD patients were recruited. At diagnosis, 160 (78.8%) and 99 (85.3%) patients with UC and CD, respectively, reported moderate-to-severe impairment in at least one PRO (p=0.18), with 89 (43.8%) and 74 (63.8%), respectively, reporting moderate-to-severe impairment in at least two PROs (p<0.01). Being female, the disease extent of UC, and extraintestinal manifestations were associated with impaired PROs. There were no differences found according to CD phenotype. FACIT-F, IBD-DI, and SIBDQ scores showed weak, but significant, correlations with the Mayo Endoscopic Score in UC, and the FACIT-F score with C-reactive protein (CRP). In CD, SIBDQ, IBD-DI, and FACIT-F correlated moderately with CRP and fecal calprotectin, but not with the endoscopic severity of CD. None of the PROs correlated with iron, ferritin, or vitamin D levels. Among the most prevalent symptoms reported were fatigue, abdominal pain, urgency, and passing of blood in both CD and UC.

Conclusion: We found a substantial patient-reported disease burden in newly diagnosed IBD, underscoring the importance of vigilant PRO monitoring in clinical practice.

Funding: This study was funded by an unrestricted grant from the Novo Nordisk Fonden.

Background and aims: Clinical decision support tools (CDSTs) have been developed to predict response to vedolizumab (VDZ) and ustekinumab (UST) in Crohn's disease (CD) and ulcerative colitis (UC). In addition to assessing their discrimination performance, our study aimed to evaluate their calibration, clinical utility and specificity.

Methods: We included 280 CD and 218 UC patients initiating VDZ, and 194 CD patients initiating UST. We assessed discrimination by comparing rates of effectiveness outcomes between response probability groups forecasted by CDSTs. Calibration curves and decision curve analysis evaluated the calibration and clinical utility of VDZ-CDSTs. Additionally, we examined the agreement between UST-CDST and VDZ-CDST in assigning response probability groups among CD patients starting UST.

Results: In the overall cohort, CDSTs allocated 7.2%, 50.0% and 42.8% of the patients to the low, intermediate and high response probability groups, respectively. VDZ-CDSTs groups demonstrated significant differences in the rates of clinical and endoscopic response and remission, while UST-CDST groups showed significant discrimination only for clinical remission. Although VDZ-CDSTs overestimated clinical remission rates, they more accurately predicted rates of VDZ persistence without need for surgery or dose escalation. Compared to empirically treating all patients with VDZ, VDZ-CDSTs yielded higher net benefits in selecting patients who would continue VDZ without need for surgery or dose escalation. Finally, the agreement between UST-CDST and VDZ-CDST in predicting response was 73.7%.

Conclusion: VDZ-CDSTs significantly discriminated response to VDZ and were more beneficial in identifying patients who would continue therapy without requiring surgery or dose escalation, compared to treating all patients empirically.

Background & aims: Despite a high prevalence of risk factors associated with hepatitis delta virus (HDV) infection among safety-net populations, data evaluating HDV testing and prevalence are limited. We aim to evaluate HDV testing practices and HDV prevalence among an ethnically diverse, multi-center cohort of safety-net patients with chronic hepatitis B (CHB).

Methods: We retrospectively evaluated 13,218 patients with CHB (54.2% male, 57.9% non-white minorities, 12.5% HIV, 23.0% HCV) across three U.S. safety-net health systems from 2010-2022 to evaluate proportion tested for HDV and proportion positive among those tested. Adjusted multivariate logistic regression models evaluated for predictors of HDV testing and predictors of anti-HDV positive.

Results: Anti-HDV testing was performed in 6.1% overall and in 4.9% that met AASLD criteria for HDV testing. Greater odds of testing was observed in men vs. women (OR 1.49, 95%CI 1.27-1.75), Asian individuals vs. white individuals (OR 2.18, 95%CI 1.74-2.72), black/African American individuals vs. white individuals (OR 1.29, 95%CI 1.07-1.56), and patients with Medicare or Medicaid. Among CHB patients tested for HDV, 15.7% were positive (22.9% among those meeting AASLD HDV testing criteria). Only 2 (1.6%) patients had follow-up HDV RNA testing. Greater proportion of anti-HDV positive was observed in patients with baseline cirrhosis (47.4% vs. 13.3%, p<0.001), and patients with Medicare or Medicaid vs. those with commercial insurance.

Conclusions: Among an ethnically diverse, multi-center safety-net cohort of CHB patients, low rates of HDV testing were observed, even among those with high-risk HDV risk factors. Among those tested, 15.7% were positive, only 2 had follow up RNA testing. This highlights the need for greater awareness, education, and advocacy to improve HDV testing rates.

Background and aims: Patients with inflammatory bowel disease (IBD) are at an increased risk for vaccine-preventable diseases, such as herpes zoster (HZ). The aim of this study was to determine whether complications of HZ are more frequent in patients with IBD than in non-IBD controls.

Methods: This was a retrospective, cohort study using the Optum Research Database. Patients with IBD were matched 1:1 to non-IBD controls based on age, sex, and index year, which was defined as the diagnosis of HZ. We then identified the complications of HZ that occurred up to 90 days after the index date. We compared patients with IBD with non-IBD controls and evaluated the 90-day risk of HZ complications. We used a composite primary outcome for any HZ complication. Secondary outcomes were risk factors for complications.

Results: Four thousand seven fifty-six patients with IBD met the inclusion criteria and were matched to the controls. Patients with IBD were more likely to have complications of HZ than controls [738 (15.52%) vs. 595 (12.51%), p < 0.0001]. Patients with IBD with higher comorbidity scores were more likely to develop complications (1.86 vs. 1.18 p < 0.0001). In the logistic regression analysis of patients with IBD having a higher comorbidity score, above 50 years of age, on anti-TNF or corticosteroids were all at increased risk of a complication of HZ.

Conclusion: Patients with IBD are more likely to have complications of HZ than controls. Efforts are needed to increase HZ vaccine uptake to reduce the morbidity of HZ.