European Journal of Gastroenterology & Hepatology最新文献

Background: Insulin resistance plays a pivotal role in the progression of type 2 diabetes mellitus (T2DM). An in-depth investigation into the role of insulin resistance scores in evaluating T2DM combined with metabolic-associated fatty liver disease (MAFLD) and liver fibrosis holds significant importance for clinical decisions and personalized treatment.

Methods: The study screened patients with diabetes from Taizhou Central Hospital from June 2020 to May 2024. In conjunction with the National Health and Nutrition Examination Survey (NHANES) database, various statistical methods such as logistic regression analysis, restricted cubic spline, and receiver operating characteristic curves were employed to complete data analysis.

Results: This study encompassed 3776 patients with T2DM, including 1074 diagnosed with MAFLD. Insulin resistance scores in the MAFLD group were significantly elevated. Compared with nonfibrotic patients, those with T2DM and liver fibrosis exhibited notably higher Chinese visceral adiposity index (CVAI) scores and notably lower triglyceride-glucose index and visceral adiposity index scores; the incidence of hypertension, coronary heart disease, stroke, and peripheral arterial disease were significantly elevated. Among other insulin resistance scores, the CVAI score demonstrated the highest value for correlating with the MAFLD and liver fibrosis in patients with T2DM. The NHANES database, encompassing data from 6763 individuals, validated the aforementioned findings, further affirming that the CVAI score exhibited optimal consistency with the risk of T2DM with MAFLD and liver fibrosis.

Conclusion: The insulin resistance scores were significantly elevated in T2DM combined with MAFLD. The CVAI score demonstrated the best predictive effect on MAFLD and liver fibrosis.

Objective: Cirrhotic patients with bacterial infections (BI) face high risks of acute-on-chronic liver failure (ACLF) and mortality. This study assessed the diagnostic value of serum complement component 3 (C3) for predicting 90-day ACLF and mortality in this population.

Methods: We prospectively analyzed clinical data from 105 cirrhotic patients with BI (mean age 57.2 ± 11.6 years; 57 male) admitted to the Second Hospital of Nanjing between September 2023 and March 2024. Primary outcomes were ACLF development and mortality within 90 days.

Results: Thirty-one patients (29.5%) developed ACLF within 90 days. Lower C3 levels independently predicted both ACLF [hazard ratio (HR): 0.14, 95% confidence interval (CI): 0.02-0.93; P = 0.04) and mortality (HR: 0.10, 95% CI: 0.00-0.89; P = 0.01). Time-dependent receiver operating characteristic analysis showed C3 predicted ACLF with AUROCs of 0.76 (30 day), 0.73 (60 day), and 0.72 (90 day). For mortality, areas under the time-dependent receiver operating characteristic curves (AUROCs) were 0.76 (30 day), 0.69 (60 day), and 0.68 (90 day). A cutoff of 0.66 g/L was established using etiology-adjusted restricted cubic spline. C3 correction improved the predictive AUROCs of Child-Turcotte-Pugh, Model of End-Stage Liver Disease, and the Chronic Liver Failure Consortium Acute Decompensation scores for mortality (all P > 0.05). Random forest regression identified C3 among the top 10 risk factors for ACLF development.

Conclusion: Serum C3 demonstrates significant prognostic value as a predictor for 90-day ACLF and mortality in cirrhotic patients with bacterial infections, offering potential clinical utility in risk stratification.

Objectives: Alarm symptoms at coeliac disease (CeD) diagnosis predict a more severe disease presentation, but the long-term implications remain unclear. We studied the prevalence of alarm symptoms at diagnosis and their association with outcomes.

Methods: A mixed-method cohort study combined retrospective medical record review with data collection through patient interviews and blood sampling from 814 adult patients with CeD after a median of 9.7 years on a gluten-free diet (GFD). Validated questionnaires assessed symptoms and quality of life. Alarm symptoms included anaemia, weight loss, dysphagia, vomiting, melaena, and rectal bleeding. Patients were grouped by the presence or absence of alarm symptoms.

Results: 45% of the patients presented with alarm symptoms, primarily (95%) anaemia and weight loss. These patients were significantly more often female (83 vs. 71%; P < 0.001), had more severe clinical presentation (P < 0.001; reported severe symptoms 41 vs. 2%) and more advanced mucosal damage (P < 0.001; subtotal or total villous atrophy 72 vs. 57%) than those without these symptoms. On GFD, these patients experienced fewer persistent symptoms (asymptomatic 71 vs. 79%; P = 0.035) but more often had osteopenia/osteoporosis (15 vs. 9%; P = 0.008). The groups did not differ in the strictness of GFD, positivity of CeD autoantibodies, quality of life, fractures, or other comorbidities.

Conclusion: Alarm symptoms were common at CeD diagnosis. After 9.7 years on a GFD, patients with alarm symptoms had a higher incidence of osteopenia/osteoporosis, but generally did not demonstrate poorer long-term outcomes compared to those without alarm symptoms.

Ectopic liver tissue (ELT) is a rare congenital anomaly characterized by hepatic parenchyma located outside the native liver. In this systematic review, 55 cases of hepatocellular carcinoma (HCC) arising from ELT were identified through a literature search performed in PubMed, MEDLINE, Scopus, and Web of Science, in accordance with PRISMA 2020 guidelines and registered in PROSPERO (CRD420251084866). The median age was 61 years (IQR: 52-68), and 65.5% were male. Hepatitis B and C were present in 26.5% cases. The most common tumor locations were the subphrenic (n = 11), peritoneal (n = 7), retroperitoneal (n = 6), and pancreatic (n = 6) regions. Solitary tumors were reported in 78.2% of cases, with a median tumor size of 71 mm (IQR: 36.5-100). AFP was elevated in 74.4% of patients, and AFP-L3 (100%) and PIVKA-II (72.7%) were elevated in most tested cases. Immunohistochemistry frequently showed positivity for HepPar-1 (88.6%), glypican-3 (81.3%), and arginase-1 (87.5%). Surgical resection was the primary treatment modality, and in addition, transarterial chemoembolization, tyrosine kinase inhibitors, and immune checkpoint inhibitors have been used as therapeutic options. The median follow-up was 17 months (IQR: 12-36), during which 85.4% of patients were alive. Distant metastasis occurred in 18.6% of cases, and local recurrence in 6.7%. In conclusion, ectopic HCC is a rare tumor entity with variable clinical presentations. Despite limited classical risk factors, surgical resection remains associated with a favorable prognosis. Histopathological confirmation is essential for diagnosis, and multimodal treatment strategies should be considered for advanced disease.

Background: The progression of hepatitis B virus-related cirrhosis (HBC) is characterized by notable intrahepatic and extrahepatic microvascular alterations and dysfunctions. The retinal vasculature offers a noninvasive window to assess systemic microcirculation. This cross-sectional study aimed to evaluate retinal microcirculatory alterations in HBC and develop a retinal vascular nomogram for diagnosing HBC.

Methods: We included 328 participants from two medical centers between March 2019 and October 2022. Multivariate logistic regression identified independent retinal predictors of HBC, and a nomogram was constructed. Associations between retinal parameters and clinical indicators of HBC were examined using univariate analyses.

Results: Retinal vascular caliber, retinal vascular branching angle, and retinal vascular fractal dimension were independent predictors of HBC. The nomogram achieved an area under the receiver operating characteristic curve of 0.778, with a sensitivity of 77.5% and specificity of 65.5%. The model demonstrated good calibration (Hosmer-Lemeshow test, P = 0.376) and significant net benefit on decision curve analysis. Internal validation confirmed its reliability. Retinal vascular alterations correlated with indicators of portal hypertension and liver insufficiency.

Conclusion: We developed a nomogram based on retinal vascular parameters to predict HBC, providing clinicians an intuitive, noninvasive diagnostic tool. The retinal microvascular alterations in HBC may reflect extrahepatic microcirculatory dysfunctions related to portal hypertension and liver insufficiency.

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.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-associated death globally. Second-line therapies are crucial for improving survival and quality of life among individuals suffering from advanced HCC who have not responded to first-line therapies. This study sought to evaluate the safety and efficacy of different second-line therapies for advanced HCC by network meta-analysis. A network meta-analysis was carried out on 26 randomized controlled trials comprising 10 368 people suffering from advanced HCC. The treatments evaluated included cabozantinib, pembrolizumab, brivanib, apatinib, and other targeted therapies. The principal results assessed included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). The evaluation also encompassed adverse events (AEs) as well as those classified as grade 3-4 AEs. Cabozantinib 60 mg once daily (QD) demonstrated the most significant improvement in OS [mean difference (MD) = 3.36, 95% confidence interval (CI) = 2.01, 4.70] and PFS (MD = 3.26, 95% CI = 2.59, 3.94), ranking highest among the therapies evaluated. Brivanib 800 mg once daily (OD) was most effective in terms of ORR [odds ratio (OR) = 7.13, 95% CI = 1.42, 35.88], while apatinib 750 mg QD ranked highest for DCR (OR = 3.92, 95% CI = 1.76, 8.71). Codrituzumab 1600 mg administered every 2 weeks demonstrated the most advantageous health profile, markedly decreasing AEs and instances of grade 3-4 AEs. Pembrolizumab 200 mg administered every 3 weeks indicated good effectiveness. Alongside a tolerable safety profile, indicating its potential as a reasonable second-line treatment option. Cabozantinib 60 mg QD and pembrolizumab 200 mg Q3W arise as the most suitable second-line therapies alternatives for advanced HCC, offering substantial improvements in survival and disease control with manageable adverse effects. These findings support the integration of both targeted and immune therapies in handling of advanced HCC.

Background: Crohn's disease (CD) and rheumatoid arthritis (RA) are autoimmune diseases. CD is known to be closely associated with RA. However, the mechanisms underlying these relationships remain unclear. This study aimed to explore the common genetic features and potential molecular mechanisms of CD and RA.

Methods: Microarray data of CD and RA in the Gene Expression Omnibus database were downloaded. Weighted gene coexpression network analysis (WGCNA) was used to identify the coexpression modules related to CD and RA. The shared genes existing in CD and RA were subjected to gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis using R software. The results were validated by differentially expressed genes (DEGs) analysis to enrich for common differential genes and unique genes in CD and RA. Based on CD-RA common hub genes, we explored the feasibility of developing new gene-antibody coupled targeted drugs for the treatment of CD-RA.

Results: Enrichment analysis of gene modules identified through WGCNA revealed disease pathway models suggesting potential mechanisms of RA secondary to CD. Furthermore, we identified key shared pathogenic genes between CD and RA, such as S100P and IL2RB that may be important targets for the treatment of both diseases.

Conclusion: The study is the first to reveal the key pathways underlying the shared pathogenesis of CD and RA, identify novel candidate genes that could serve as biomarkers or potential therapeutic targets. Finally, we propose new ideas for the development of gene-antibody coupled targeted drugs.