European Journal of Gastroenterology & Hepatology最新文献

Introduction: While antineutrophil cytoplasmic antibody (ANCA)-associated small-vessel vasculitis (AAV) is increasingly recognized, cases presenting with initial gastrointestinal symptoms remain underexplored. This study aimed to analyze the clinical characteristics of AAV patients with gastrointestinal onset.

Methods: Seven AAV patients meeting ACR/EULAR criteria, who presented with gastrointestinal symptoms between January 2017 and 2024, were retrospectively identified. A literature review was conducted across multiple databases, including PubMed, Web of Science, Cochrane Library, Embase, CNKI, VIP, and Wanfang. In total, 23 patients were included in the study.

Results: Among the 23 AAV patients with gastrointestinal symptoms, 15 (65.2%) were male, with a median age of 54 years (range: 18-79). Common clinical manifestations included hematochezia (56.5%), weight loss (43.5%), and purpura (34.8%). Eight (34.8%) had superficial gastritis, and seven (30.4%) had colonic ulcers, as identified by gastrointestinal endoscopy. Laboratory findings revealed elevated D-dimer levels and anemia in most patients, with impaired renal function and a median hemoglobin level of 105 g/L. Anti-PR3 immunoglobulin G (IgG) and antimyeloperoxidase IgG antibodies were positive in 83.3 and 80% of cases, respectively. Abdominal computed tomography (CT) revealed wall thickening in 39.1% of patients, and chest CT identified interstitial lung disease in 73.9% of patients. Nine patients (39.1%) were initially misdiagnosed, with five (55.6% of those nine) misdiagnosed as having inflammatory bowel disease. Most patients responded well to glucocorticoid and immunosuppressive therapy, with 39.1% receiving a combination of glucocorticoids and cyclophosphamide.

Conclusion: Gastrointestinal symptoms in AAV are rare, and misdiagnosis remains a concern. Early detection requires assessing gastrointestinal, pulmonary, and renal involvement.

Background and aim: Lactulose and rifaximin are recommended therapies for hepatic encephalopathy. Although the usefulness of the combination is evident, there is a paucity of real-world data regarding the efficacy of lactulose and rifaximin combination therapy when used immediately after overt hepatic encephalopathy (OHE) onset. This study aimed to clarify the prophylactic effect of using combination therapy as a first-line treatment in real-world clinical practice.

Methods: In this retrospective cohort study, 96 patients who had developed OHE and subsequently improved were included. As first-line prophylactic therapy, 37 patients received lactulose and rifaximin combination therapy, while 59 patients received lactulose monotherapy. The primary outcome was OHE recurrence within 12 months.

Results: The cohort represented a real-world Japanese population of elderly patients with advanced cirrhosis. The 12-month cumulative incidence rates of OHE recurrence were significantly lower in the combination therapy group (25.0%) compared with the monotherapy group (49.3%) (Gray's test P  = 0.026). In the Fine-Gray multivariable analysis, combination therapy significantly reduced recurrence risk, with a subdistribution hazard ratio of 0.44 (95% confidence interval: 0.20-0.97).

Conclusion: Lactulose and rifaximin combination therapy significantly suppressed OHE recurrence more effectively than lactulose monotherapy when used as a first-line treatment. Our findings suggest clarify the prophylactic benefit of the two-drug combination; this therapy may be a more useful first-line treatment for patients with OHE and could be recommended.

Objective: Hepatitis B virus (HBV) can persist in peripheral blood mononuclear cells (PBMCs) as an extrahepatic reservoir in treatment-naive patients; however, its persistence during long-term nucleos(t)ide analogue therapy with sustained serum viral suppression remains unclear. This study aimed to evaluate the frequency and predictors of HBV DNA detectability in PBMCs of chronic hepatitis B (CHB) patients following long-term nucleos(t)ide analogue therapy-induced sustained serum viral suppression.

Methods: Eighty-eight CHB patients, on long-term tenofovir disoproxil fumarate ( n = 44) or entecavir ( n = 44) with greater than 2 years of sustained viral suppression, were enrolled. PBMCs were tested for HBV DNA by quantitative PCR. Clinical and laboratory data were analyzed to identify predictors of PBMC HBV DNA detection. Receiver operating characteristic analysis assessed the performance of posttreatment serum quantitative hepatitis B surface antigen (qHBsAg).

Results: HBV DNA was detected in PBMCs of eight (9.1%) patients, equally distributed between treatment groups. Pretreatment hepatitis B e-antigen (HBeAg) positivity predicted PBMC HBV DNA detection ( P = 0.036). PBMC HBV DNA-positive patients were older males with worse baseline liver chemistry and advanced fibrosis. Posttreatment qHBsAg was higher in PBMC HBV DNA-positive patients (139.5 vs. 21.5 IU/ml; P < 0.001) and strongly correlated with PBMC viral load ( r = 0.905, P = 0.002); qHBsAg greater than 89 IU/ml predicted PBMC HBV DNA detection with high accuracy.

Conclusion: HBV DNA may persist in PBMCs despite long-term nucleos(t)ide analogue therapy-induced sustained viral suppression. Pretreatment HBeAg positivity and elevated posttreatment qHBsAg can help identify patients at risk, highlighting the need to monitor extrahepatic reservoirs in CHB management.

Background: Nonalcoholic fatty liver disease (NAFLD), which affects approximately 25% of the global adult population, is a metabolic-associated hepatic disorder characterized by the interplay between inflammation and metabolism. Although evidence linking inflammatory factors and plasma metabolites to NAFLD progression, their causal relationships and mediating mechanisms remain unclear.

Methods: This study employed a bidirectional Mendelian randomization (MR) approach combined with mediation analysis to investigate the causal relationships between inflammatory factors, plasma metabolites, and NAFLD. Summary data for 91 inflammatory factors and 1400 plasma metabolites were extracted from the genome-wide association studies databases and analyzed using MR. Mediation analysis was performed to examine whether the nine selected metabolites mediated the relationship between the eight inflammatory factors and NAFLD. All the analyses included tests for heterogeneity and pleiotropy.

Results: This study identified 11 inflammatory factors and 110 plasma metabolites that were significantly associated with NAFLD. Mediation analysis revealed that specific metabolites, including pregnenetriol disulfate, alanine: asparagine ratio, and X-21471, mediate the relationship between inflammatory factors and NAFLD. Notably, X-21471 was identified as a shared mediator of both tumor necrosis factor receptor superfamily member 9 (TNFRSF9) and CCL20.

Conclusion: This integrative MR mediation analysis delineates an inflammation-metabolism-NAFLD axis, in which specific metabolites (X-21471, pregnenetriol disulfate) transmit pro-inflammatory signals (TNFRSF9/CCL20) involved in NAFLD pathogenesis. These findings suggest that combined targeting of TNFRSF9 and X-21471 may represent a precise preventive strategy for high-risk populations with metabolic comorbidities.

Background/aims: In patients with advanced chronic liver disease, acute gastrointestinal bleeding can be classified as acute variceal bleeding or nonvariceal bleeding. We aim to compare clinical outcomes between variceal and nonvariceal bleeding in patients with advanced chronic liver disease and to identify predictors of liver-related death following variceal bleeding.

Methods: Retrospective, observational, and unicenter study. Patients with advanced chronic liver disease presenting with acute gastrointestinal bleeding between 2016 and 2022 were divided into variceal and nonvariceal bleeding groups. Complications, rebleeding, further decompensation, and liver-related death were compared.

Results: In total, 154 patients were included. Nonvariceal bleeding group (n = 57) was older (P < 0.001), with higher model for end-stage liver disease-sodium (MELD-Na) (P = 0.016) and ascites at admission (P = 0.033). In-hospital mortality (P = 0.101), complications (P = 0.362), rebleeding (P = 0.102), further decompensation (P = 0.112), and liver-related death in the follow-up (P = 0.112) were similar between groups. In the variceal bleeding group, MELD-Na predicted liver-related death within 30 (P < 0.001) and 90 days (P < 0.001). Variceal bleeding, whether as a first or further decompensation event, was associated with similar risks of 30-day readmission and liver-related death.

Conclusion: There were no significant differences in outcomes between groups. In the variceal bleeding group, MELD-Na was an independent predictor of liver-related death within 30 and 90 days.

Objectives: VE202 is an oral, defined 16-strain bacterial consortium with properties that may diminish dysbiosis and alleviate symptoms of inflammatory bowel disease. This phase 1 study evaluated VE202 safety and tolerability and assessed strain colonization.

Methods: Thirty-one healthy adults received oral vancomycin 125 mg four times daily for 5 days to decrease gut microbial burden, followed by a single dose of VE202 at 1 × 10 9 or 1 × 10 10 colony-forming units (CFUs), or 14-days of the lower dose (1.4 × 10 10 total CFU). Adverse events were monitored through week 12, with follow-up at week 24. Stool was collected for VE202 strain detection and abundance during screening and pretreatment, day 2, day 4, day 7, day 14, week 4, week 8, week 12, and optionally at week 24.

Results: VE202 and vancomycin pretreatment were well tolerated. Among VE202 recipients, the most frequent adverse events (>20% of subjects) were abdominal discomfort, diarrhea, headache, and fatigue. Most treatment-related adverse events were gastrointestinal. Two serious adverse events were reported; these were not treatment-related and occurred weeks after dosing completion. VE202 strain detection and relative abundance in the vancomycin-perturbed gut occurred as soon as day 2, sustained through 2 weeks postdosing, then declined slowly but remained substantially above baseline through week 24. Colonization was dose- and duration-dependent, with 14-day dosing providing more durable VE202 colonization.

Conclusion: VE202 was well tolerated. Following antibiotic pretreatment, rapid and durable gut colonization of VE202 strains was observed, most significantly in participants administered multiple doses (NCT03931447).

Inflammatory bowel disease (IBD) patients undergoing antitumor necrosis factor-alpha (anti-TNF) therapy are at increased risk of developing tuberculosis (TB), making screening before anti-TNF initiation mandatory. Repeated screening during treatment is not yet recommended because of a lack of studies to support this practice. We aimed to determine the proportion of patients who develop latent TB during anti-TNF therapy. We systematically searched studies from MEDLINE, Embase, and Lilacs, and performed a single-arm meta-analysis investigating the positive conversion rate in IBD patients under anti-TNF therapy with previous negative TB screening. We calculated the combined proportion with 95% confidence interval, using the random-effects model. A P value less than 0.05 was considered statistically significant for subgroup differences. We included 13 studies from nine countries with 1153 patients. The overall positive conversion rate was 9.20%. Portugal had 18.01% of positive conversion, Spain 4.51%, and the USA 1.11%. Tests for subgroup differences were statistically significant for subgroup analysis by country and consistency of test used (performig same test as baseline). Subgroup analyses by continent, study design, or specific test (tuberculin skin test or interferon-gamma release assay) showed no statistical difference. Meta-regression analysis showed a significant positive association between positive conversion and TB incidence. In conclusion, IBD patients on anti-TNF therapy can have a positive conversion rate of 9.20%. Higher conversion rates were seen in European and Asian studies compared with those in the Americas (particularly the USA). TB prevention strategies should, therefore, be individualized and based on geographic location and risk factors.

Objectives: There are limited data regarding adalimumab (ADM) clearance in inflammatory bowel disease (IBD). The aim of this study was to identify factors associated with ADM clearance and to assess its association with mucosal healing.

Methods: This single-center, retrospective study included consecutive patients with IBD who received maintenance ADM therapy and underwent therapeutic drug monitoring (TDM) between January 2018 and May 2023. Drug clearance was determined using a nonlinear mixed-effect model with Bayesian priors. Mucosal healing was defined as an endoscopic Mayo score 1 or less; for ulcerative colitis, no ulcerations for patients with Crohn's disease, or a Rutgeerts score of i1 or less for patients with an ileocolonic resection for Crohn's disease and was evaluated within 3 months from TDM.

Results: The study population consisted of 263 patients with IBD (74% Crohn's disease) who underwent a total of 515 TDM tests (388 proactive). Multivariable linear regression analysis identified that proactive TDM was associated with lower ADM clearance [beta coefficients (β): -0.173, 95% confidence interval (CI): -0.180 to -0.088, P < 0.001], while BMI (β: 0.125, 95% CI: 0.005-0.013, P < 0.001), prior biologic exposure (β: 0.087, 95% CI: 0.022-0.112, P = 0.004), and antibodies to ADM (β: 0.676, 95% CI: 0.628-0.750, P < 0.001) were associated with higher ADM clearance. Receiver operating characteristic analysis identified an ADM clearance threshold of 0.301 L/day (area under the receiver operating characteristic curve: 0.731; 95% CI: 0.654-0.808; P < 0.001; sensitivity: 61%; specificity: 78%) distinguishing patients with or without mucosal healing.

Conclusion: This study demonstrated that lower ADM clearance is associated with proactive TDM and mucosal healing in patients with IBD.