Clinical Gastroenterology and Hepatology最新文献

Background & aims: COVID-19 infection may increase the risk of developing disorders of gut-brain interaction (DGBI). However, the extent of this effect on a population level is poorly understood. We performed a 2-country survey to address this issue.

Methods: A population-based Internet survey with predefined demographic quotas was conducted across the United Kingdom (UK) and United States (U.S.) in 2017 (pre-pandemic; n = 4050) and repeated in 2023 (post-pandemic; n = 4002). The surveys included the Rome IV diagnostic questionnaire, and questions about nongastrointestinal somatic symptoms, anxiety and depression, quality of life, and health care utilization. The 2023 survey also included questions regarding COVID-19 infection and illness history.

Results: The overall DGBI prevalence (ie, meeting diagnostic criteria for at least 1 DGBI) has significantly increased from the pre- to post- pandemic era (38.3% vs 42.6%; odds ratio [OR], 1.20; 95% confidence interval, 1.09-1.31), with similar findings independently noted in the UK and U.S. The rise in DGBI was observed within the esophageal (8.8% vs 10.1%; OR, 1.16), gastroduodenal (11.9% vs 16.4%; OR, 1.45), and bowel domains (30.1% vs 32.5%; OR, 1.12). The 2 most widely investigated DGBIs showed large post-pandemic prevalence increases, with functional dyspepsia rising from 8.3% to 11.9% (OR, 1.48) and irritable bowel syndrome from 4.7% to 6.0% (OR, 1.31). In multivariable analysis, factors significantly associated with having DGBI in the post-pandemic era included younger age, female sex, anxiety, depression, medium-to-high somatic symptom severity, increasing number of COVID-19 infections, experiencing abdominal pain or diarrhea during COVID-19 infection, and suffering with long COVID. Individuals with DGBI in the post-pandemic era, in particular those with long COVID, reported reduced quality of life and higher mood disturbances, somatic symptom reporting, and health care use than individuals with DGBI in the pre-pandemic era.

Conclusions: The population prevalence and burden of DGBI have increased following the COVID-19 pandemic. Health care services and research funding bodies need to adapt to this post-COVID rise in DGBI and address how to best manage this patient group.

Background & aims: Cross-sectional imaging is an integral part of evaluating disease activity and complications in Crohn's disease. There remains a need to develop guidance that may be for both clinical trials and clinical practice. This initiative aimed to develop consensus statements for definitions of response and remission, transmural healing, optimal timing for assessing, and evaluation of treatment efficacy in patients with Crohn's disease using magnetic resonance enterography in clinical trials and clinical practice.

Methods: Thirty-three international experts (gastroenterologists [n = 29] and radiologists [n = 4] participated in a consensus process. A systematic literature review was conducted to inform initial consensus, and statements were discussed and voted on using a modified Delphi method. Consensus was defined as at least 75% agreement among voters.

Results: The Magnetic Resonance Index of Activity (MaRIA) score and the simplified MaRIA score should be used to determine response and remission in moderate-to-severe Crohn's disease. Response was defined as a MaRIA score <11 or an improvement of at least 25%, and a decrease of at least 1 point in the simplified MaRIA score. Remission was defined as a MaRIA score <7 or a simplified MaRIA score <1. Five different definitions were proposed for transmural healing. For the time point of assessment, the group proposed week 24 for response; weeks 24, 52, or 54 for remission; and weeks 52 or 104 for transmural healing.

Conclusions: A consensus expert panel has developed standardized definitions of magnetic resonance enterography response, remission, and the optimal timing for response assessment in patients with luminal Crohn's disease. Further research is needed to clarify the method for measuring transmural healing.

Background & aims: Management of patients with autoimmune hepatitis (AIH)-related decompensated cirrhosis is challenging because of the risk of treatment-related complications and lack of clinical recommendations. We investigated the predictive factors for treatment benefit in AIH-related decompensated cirrhosis at diagnosis and developed an algorithm to guide treatment decisions in clinical practice.

Methods: This retrospective, international, multicenter study included 232 patients with histologically confirmed AIH-related decompensated cirrhosis at diagnosis. The sub-hazard ratio (SHR) of mortality was determined by competing risk analysis, considering liver transplantation (LT) as competing event. A decision tree analysis was used to develop a treatment algorithm.

Results: At diagnosis, 89% of patients had ascites, and 41% had overt hepatic encephalopathy (OHE). Treated patients (n = 214; 92%) had higher aminotransferases, bilirubin, and modified hepatic activity index. The SHR of mortality was lower in treated patients (0.438; 95% confidence interval [CI], 0.196-0.981; P = .045). Patients without OHE grade 3/4 and Model for End-Stage Liver Disease-Sodium (MELD-Na) ≤28 at diagnosis were more likely to benefit from treatment. In these patients, a decline in MELD-Na ≥11 after 4 weeks of treatment had a 100% negative predictive value for death/LT. Forty-nine percent of treated patients recompensated during follow-up. Twenty percent of patients had to discontinue treatment, 65% during the first 4 weeks, and only 4% due to infectious complications. OHE ≥grade 2 and MELD-Na at diagnosis predicted the need for treatment discontinuation.

Conclusions: Immunosuppression is beneficial in patients with AIH-related decompensated cirrhosis and active disease. OHE and MELD-Na at diagnosis, along with a decline in MELD-Na at 4 weeks of treatment, are the most important determinants of outcome and can guide treatment decisions.

Background & aims: Resmetirom is the first Food and Drug Administration-approved drug for metabolic dysfunction-associated liver disease (MASLD) in F2 and F3 patients with steatohepatitis. Noninvasive criteria have been proposed for initiating treatment; however, these have not been validated in clinical practice. We validated the proposed criteria and established new guidelines for initiating resmetirom treatment in clinical practice.

Methods: This was a cross-sectional study of 1281 MASLD patients from the HEPAmet registry with biopsy, comorbidity assessment, analytical profile, and elastography. Identification of MASLD with F2 and F3 was the main endpoint. A comprehensive review of international guidelines and expert consensus up to November 2024, focusing on therapeutic indications, was conducted.

Results: A total of 38% (n = 486 of 1281) of patients were diagnosed with MASLD F2 and F3 based on biopsy. However, only 39% and 56% of them met treatment eligibility criteria according to the Expert Panel Criteria and the American Association for the Study of Liver Diseases Practice Guidance, respectively. They included 45% of patients with early-stage fibrosis. False positive and false negative rates ranged from 23% to 41% and 44% to 60%, respectively, with area under the receiver-operating characteristic curve values below 0.60.These findings were validated in an external cohort. A two-step strategy, first selecting patients with Fibrosis-4 (FIB-4) ≥1.30, or with diabetes and overweight if FIB-4 <1.30, followed by a liver stiffness between 8 and 25 kPa, demonstrated higher positive (55%) and negative predictive values (77%) and higher area under the receiver-operating characteristic curve (0.67).This approach successfully identified 74% of the target population.

Conclusions: The diagnostic performance and reliability of the proposed noninvasive criteria for initiating resmetirom treatment were suboptimal. About the half of patients with indication would not receive treatment under these criteria. A new strategy, using FIB-4, the presence of diabetes and overweight, and liver stiffness improved the identification of MASLD patients with F2 and F3.

Background & aims: Topical corticosteroids represent one of the effective first-line treatment options for eosinophilic esophagitis (EoE), and therapy with budesonide orodispersible tablets (BOTs) has been recently approved for the treatment of EoE and showed great efficacy in randomized-controlled clinical trials, however real-life data are lacking. Thus, we aimed to evaluate the effectiveness of treatment with BOTs in adult EoE patients in a real-life setting.

Methods: In this prospective study, clinical, histologic, endoscopic, and safety measures were assessed. Patients underwent evaluation after the induction period (12 weeks) and up 1 year of treatment with BOTs. Dysphagia Symptom Questionnaires were used for symptoms; the Adult Eosinophilic Esophagitis Quality of Life questionnaire for quality of life; the Endoscopic Reference Score for endoscopic activity; eosinophilic peaks (eosinophils per high-power field) for histologic activity.

Results: A total of 233 patients were enrolled and 203 completed the assessments after 12 weeks. Deep histological remission was achieved by 84% of patients, as well as clinical remission, associated with an improvement in quality of life. Eighty-six patients concluded 1 year of treatment, and 78% were still in deep remission, while 15% experienced a loss of histological response at treatment tapering. Primary nonresponders were 8%, and secondary nonresponders were 3%. No serious adverse effects were recorded. Only mild side effects related to drug assumption were reported by 28 (12%) of 233 patients, and the most common were oral symptoms.

Conclusions: Our real-world data confirm that BOTs are effective in inducing clinical and histologic remission in most EoE patients. The drug has a good safety profile, with side effects occurring only in a small number of patients.

Background & aims: Dietary emulsifier consumption might promote intestinal inflammation, eventually leading to inflammatory bowel diseases. However, human data are scarce and involve a limited number of emulsifiers. We studied the effects of an emulsifier-free diet (EFD) and specific emulsifier supplementation.

Methods: Sixty healthy participants followed an EFD for 2 weeks. Then, using a randomized placebo-controlled trial design, participants continued an EFD for 4 weeks with the addition of either carboxymethyl cellulose, polysorbate-80, carrageenan, soy lecithin, native rice starch, or no additives administered through brownies. Effects on cardiometabolic markers, gut microbiota, intestinal inflammation, and permeability were explored.

Results: After 2 weeks of an EFD, cholesterol levels decreased (P = .00006). Under emulsifier supplementation, alpha diversity remained stable, yet microbial composition was affected by treatment and visit. Compared with placebo, concentrations of all short chain fatty acids were lower in those consuming carboxymethyl cellulose, which was mirrored by other emulsifiers, although not all reached significance. No differences in fecal calprotectin, C-reactive protein, serum lipopolysaccharide-binding protein, cholesterol levels, or other metabolic markers were observed between placebo and emulsifiers at the end of the intervention. Serum inflammatory and cardiometabolic proteins remained unchanged. In individuals consuming carrageenan, transcellular intestinal permeability increased (P = .04) compared with baseline.

Conclusions: In this double-blind placebo-controlled exploratory trial, emulsifier supplementation lowered short chain fatty acid concentration compared with placebo. Emulsifier supplementation did not impact intestinal or systemic inflammation or metabolic endpoints. Cholesterol levels decreased after 2 weeks of an EFD. These results point towards potential intestinal benefits of limiting dietary emulsifiers in the diet, requiring further investigation.

Clinicaltrials: gov, Number: NCT06552156.