World Journal of Gastroenterology最新文献

Background: Hepatitis B-related cirrhosis represents a major contributor to liver-related events (LREs), with the development of clinically significant portal hypertension (CSPH) serving as a critical milestone in disease progression.

Aim: To establish predictive models based on multiple machine learning algorithms to improve the accuracy and clinical utility of LREs prediction.

Methods: A total of 576 patients were retrospectively enrolled and randomly divided into training (n = 403) and validation (n = 173) cohorts. Features were selected through least absolute shrinkage and selection operator regression, random forest (RF), and support vector machine (SVM). Based on these features, five predictive models were constructed, including SVM, RF, logistic regression, extreme gradient boosting (XGBoost), and k-nearest neighbor. Model performance was evaluated using receiver operating characteristic and decision curve analysis, and feature importance and interactions were further explored using SHapley Additive exPlanations (SHAP).

Results: Of the patients included, 313 (54.3%) developed LREs. Eight core predictive features were ultimately identified, with the liver stiffness measurement (LSM)-to-platelet ratio (LPR) contributing most significantly. The XGBoost and RF models demonstrated superior performance, achieving accuracies of 0.951 and areas under the curve of 0.975 and 0.965, respectively. SHAP analysis revealed that LPR, hemoglobin (HB), and LSM were key factors, with LPR exhibiting significant interactions with HB, international normalized ratio, and spleen thickness.

Conclusion: Machine learning-based prediction models, particularly XGBoost and RF, can effectively identify high-risk individuals among patients with compensated hepatitis B virus-related cirrhosis and CSPH. LPR that incorporates LSM is a valuable and robust predictive indicator.

Background: Portal vein thrombosis (PVT) is a rare condition and is often associated with cirrhosis, malignancy, or prothrombotic states. Currently, systemic anticoagulation is the standard to treat PVT. The role of alternative treatments are currently under investigation. In particular direct thrombolysis for the treatment of nonmalignant PVT is controversial due to the risk of bleeding. Here we have reported a case highlighting therapeutic considerations and outcomes of direct thrombolysis.

Case summary: A 67-year-old male without a prior history of cirrhosis or malignancy presented with acute abdominal pain and peritonitis. Contrast-enhanced computed tomography revealed complete thrombosis of the portal vein with extension into the superior mesenteric vein. These findings were consistent with impending mesenteric ischemia. Despite systemic anticoagulation the patient's symptoms progressed. Urgent catheter-directed thrombolysis via a transhepatic approach was initiated using continuous urokinase infusion. We observed substantial thrombus regression and resolution of ischemic symptoms, thereby avoiding surgical intervention. Subsequent hematologic evaluation revealed a JAK2 V617F mutation-associated polycythemia vera as the underlying prothrombotic disorder.

Conclusion: Early low-dose catheter-directed thrombolysis provided a safe and effective treatment for a patient with noncirrhotic, nonmalignant PVT associated with mesenteric ischemia, demonstrating the utility of an alternative treatment for PVT.

Alpha-gal syndrome (AGS), an emerging tick-borne carbohydrate hypersensitivity, has gained increasing recognition for its atypical presentation and delayed food-related allergic reactions. While urticaria and anaphylaxis dominate the clinical narrative, gastrointestinal (GI) manifestations-including abdominal pain, diarrhea, bloating, and cramping-are common and often underrecognized. These nonspecific GI symptoms create significant diagnostic overlap with prevalent functional and food-related disorders such as non-celiac gluten sensitivity (NCGS) and lactose intolerance. Consequently, many patients with AGS undergo unnecessary dietary restrictions, prolonged symptom burden, or misdirected therapies before an accurate diagnosis is established. The knowledge gap lies in the limited awareness of AGS as a differential diagnosis for food-related GI complaints, especially in regions endemic to tick exposure. Unlike gluten or lactose intolerance, AGS reactions are characterized by a unique delayed onset (2-6 hours postprandially) and a distinct immunologic mechanism mediated by IgE to galactose-α-1,3-galactose. However, clinicians rarely consider AGS when evaluating chronic, unexplained food-triggered symptoms, perpetuating diagnostic blind spots. Current guidelines for evaluating NCGS and lactose intolerance seldom incorporate testing for alpha-gal IgE, despite growing evidence that a subset of misdiagnosed patients may in fact harbor AGS. Clinically, this misclassification carries significant consequences: Patients may continue mammalian food exposure with risk of escalating allergic reactions, including life-threatening anaphylaxis, while adhering to unnecessary or ineffective gluten-free or lactose-free diets. Raising awareness, integrating alpha-gal IgE testing into gastroenterology workups, and refining diagnostic algorithms are urgently needed. Addressing this blind spot has the potential to reduce morbidity, improve diagnostic accuracy, and optimize individualized patient care.

The treatment landscape of hepatocellular carcinoma (HCC) has significantly evolved following the introduction of immune checkpoint inhibitors (ICIs), which are now the standard of care in first-line systemic therapy. However, as more patients experience progression after ICI-based combinations, the optimal second-line treatment strategy remains undefined. Currently approved agents, such as regorafenib, cabozantinib, and ramucirumab, have not been specifically tested in the post-ICI setting, and their efficacy in this context remains uncertain. This review provides a comprehensive and critical analysis of systemic second-line treatment strategies in patients with unresectable HCC after progression to frontline immunotherapy. We summarize the available evidence from early-phase studies and retrospective series and describe the rationale, efficacy signals, and development status of ongoing clinical trials. Therapeutic approaches include tyrosine kinase inhibitors, novel ICI-based combinations, bispecific antibodies, T-cell therapies (chimeric antigen receptor-T and T-cell receptor-T), and other emerging strategies such as liver-targeted prodrugs and microbiota modulation. While current data are still limited, several trials are ongoing and reflect compelling biological hypotheses. Their diversity highlights both the complexity and the opportunity of this therapeutic space. Future research should focus on identifying predictive biomarkers, optimizing safety, and developing individualized sequencing strategies to enhance outcomes in this rapidly expanding patient population.

Background: Over recent decades, treatment for human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infection has significantly advanced. HIV is known to accelerate liver disease progression and increase liver-related mortality in patients with HCV infection.

Aim: To reassess the effectiveness of HCV treatments by comparing outcomes between HIV/HCV co-infected and HCV mono-infected patients.

Methods: We retrospectively included patients with HCV mono-infection or HIV/HCV co-infection at 12 tertiary referral centers from January 2009 to December 2020. The primary endpoint was overall survival (OS). Secondary endpoints included achievement of a sustained virologic response (SVR), time-to-occurrence of hepatocellular carcinoma (HCC), and the changes in fibrosis-4 (FIB-4) index.

Results: A total of 904 patients were included: 792 with HCV mono-infection and 112 with HIV/HCV co-infection, of whom 97 (86.6%) had received prior HIV treatment. HCV treatment was administered to 741 (93.6%) mono-infected and 86 (76.8%) co-infected patients. Among treated patients, SVR was achieved in 93.4% of mono-infected and 81.4% of the co-infected group [P = 0.114 after inverse probability of treatment weighting (IPTW) adjustment]. OS and HCC occurrence showed no significant differences between groups, regardless of the HCV treatment method, after IPTW [hazard ratio (HR) = 0.37, 95% confidence interval (95%CI): 0.05-3.07, P = 0.360 for OS; HR = 0.19, 95%CI: 0.02-1.48, P = 0.113 for HCC occurrence]. The FIB-4 index significantly improved 1 year after achieving SVR with direct-acting antivirals in both groups.

Conclusion: With optimal HIV/HCV treatment regimens, HCC occurrence and mortality risks in co-infected patients have become comparable to those in patients with HCV mono-infection.

Gastric ulcer remains a common cause of morbidity, yet marked clinical variability suggests contributors beyond established risk factors such as Helicobacter pylori, non-steroidal anti-inflammatory drug exposure, and excess gastric acid. To clarify the role of systemic inflammation, Shen et al evaluated six complete blood count (CBC)-derived inflammatory indices in patients with gastric ulcer. All indices showed significant associations, with the systemic inflammatory response index demonstrating the strongest discriminatory value. Given that CBC testing is routine, inexpensive, and widely accessible, these indices may offer practical adjunctive markers for identifying individuals at increased risk. However, the cross-sectional design and lack of adjustment for major confounders limit causal interpretation. Prospective validation is required to determine whether these indices predict ulcer development, recurrence, or clinical outcomes, and to assess their potential integration with established risk factors.

Background: Incomplete resection of rectal neuroendocrine tumors (NETs), defined by positive or indeterminate margins or lymphovascular invasion, raises concerns regarding residual disease and recurrence. However, the benefits of salvage treatment in these cases remain unclear.

Aim: To evaluate the oncologic impact of salvage treatment compared with observation after incomplete endoscopic resection of rectal NETs through a systematic review and meta-analysis.

Methods: We conducted a systematic review and meta-analysis in accordance with the preferred reporting items for systematic reviews and meta-analyses guidelines. MEDLINE, EMBASE, and the Cochrane Library were searched from their inception until May 2025. Eligible studies included patients with incompletely resected rectal NETs managed with salvage treatment or observation, reporting outcomes of residual tumors or recurrence. Pooled estimates were calculated using random-effects models with Hartung-Knapp adjustments.

Results: Thirty-four studies with 2279 cases of incomplete endoscopic resection met the inclusion criteria. The incomplete resection rates differed markedly according to the initial resection method (17 studies): 73.1% for cold snare polypectomy, 29.8% for conventional endoscopic mucosal resection (EMR), 28.4% for modified EMR, and 14.7% for endoscopic submucosal dissection. Among the 19 studies that evaluated salvage treatment, the pooled residual tumor rate was 25.0% [95% confidence interval (CI): 12.0%-40.0%]. The crude recurrence rates from 31 studies favored salvage treatment over observation (0.96% vs 2.96%, P = 0.003). However, a meta-analysis of nine comparative studies found no statistically significant difference in recurrence risk (odds ratio = 0.89; 95%CI: 0.40-2.02).

Conclusion: Given the relatively high residual tumor rate and low incidence of recurrence, salvage treatment may be justified as both a diagnostic and therapeutic approach after incomplete resection of rectal NETs. Although its benefits in preventing recurrence remain unclear, clinical decisions should be individualized, as these findings are based on low-certainty evidence.

Background: Cluster of differentiation 24 (CD24) serves as a liver cancer stem cell marker, and its upregulation is related to chronic liver disease malignancy. However, the exact relationship between CD24 expression and hepatocarcinogenesis remains unknown.

Aim: To investigate CD24 levels among individuals with chronic liver diseases and confirm the alterations in CD24 and programmed death-ligand 1 (PD-L1) expression in a dynamic model of rat hepatocarcinogenesis.

Methods: Approved by the ethics committee, CD24 levels were detected in the serum of 129 patients with hepatocellular carcinoma (HCC), 72 patients with chronic hepatitis (CH), 60 patients with liver cirrhosis (LC) and 111 normal control (NC). Receiver operating characteristic curves and clinicopathological characteristics of CD24 were used to evaluate the diagnostic or prognostic value for HCC, and the CD24⁺ T lymphocyte ratio and dynamic alterations in CD24 and PD-L1 expression were confirmed in a rat HCC model.

Results: Compared with those in the CH, LC and NC groups, the average CD24 level in the HCC group was significantly greater (P < 0.01). The CD24⁺ T-cell ratio in the HCC group was greater than that in the CH or NC group. Clinicopathological characteristics of high CD24 in HCC patients included hepatitis B virus infection, single/multicenter status, tumor size, lymph node or extrahepatic metastasis, differentiation degree, tumor-node-metastasis grade, Child-Pugh score, portal vein tumor thrombus and poor prognosis. Mechanistically, CD24 is dynamically upregulated during hepatocarcinogenesis and closely positively correlated with PD-L1 for immune escape, metastasis (CD44), and with respect to HCC markers (Wnt3a, GPC-3 and alpha-fetoprotein).

Conclusion: Activated CD24 promoted HCC formation through programmed death-ligand 1 signaling and could be a valuable biomarker for monitoring chronic liver disease malignancy.

Acute pancreatitis (AP) remains a challenging clinical condition with limited therapeutic options and high mortality rates in severe cases. Traditional anti-inflammatory approaches have shown disappointing results in clinical trials, highlighting the urgent need for novel therapeutic strategies targeting the underlying pathophysiological mechanisms. The study by Jia et al presents compelling evidence for a previously unrecognized mechanism through which rutaecarpine, a bioactive alkaloid from traditional Chinese medicine, exerts protective effects against AP. This research demonstrates that rutaecarpine alleviates AP by targeting the epigenetic machinery, specifically through enhancer of EZH2-mediated suppression of FBXW11. The authors employed both in vitro cerulein-induced AR42J cell models and in vivo sodium taurocholate-induced rat models to establish the therapeutic efficacy of rutaecarpine and elucidate its molecular mechanisms. Their findings reveal that rutaecarpine upregulates EZH2 expression, leading to increased histone H3 methylation at the FBXW11 promoter region, thereby suppressing FBXW11 expression and consequently reducing inflammatory infiltration and oxidative stress. The significance of this work extends beyond demonstrating rutaecarpine's protective effects. It identifies FBXW11 as a novel therapeutic target in AP and provides the first evidence that traditional Chinese medicine compounds can modulate epigenetic reprogramming in pancreatic inflammation. Recent studies have confirmed FBXW11's role as an inflammatory biomarker in pancreatitis, supporting the clinical relevance of this pathway. The study's comprehensive approach, combining molecular docking, cellular thermal shift assays, and co-immunoprecipitation studies, strengthens the mechanistic insights. These findings open new avenues for AP treatment by targeting epigenetic regulators rather than relying solely on conventional anti-inflammatory strategies, potentially leading to more effective therapeutic interventions for this devastating condition.

Serum gamma-glutamyl transferase (GGT), a marker of hepatobiliary and oxidative stress, emerged as a predictor of incident pancreatic cystic neoplasms (PCNs) in a 2.65-million nationwide cohort followed for > 10 years. The highest GGT quartile conferred 11% excess PCN risk, with hazard ratios rising across quartiles and persisting after 3- and 5-year lag exclusions. In redox-oncology, pancreatic GGT1 isoform upregulated by oncogenic KRAS cleaves extracellular glutathione, promoting reactive oxygen species-mediated DNA damage, Wnt/β-catenin, and interleukin-6/signal transducer and activator of transcription 3 inflammatory circuits cooperating with GNAS mutations to initiate intraductal papillary mucinous neoplasm. We propose: (1) Refining age-specific GGT thresholds via repeated measurements and restricted cubic splines; (2) Integrating GGT with carbohydrate antigen 19-9, carcinoembryonic antigen, and KRAS/GNAS circulating tumor DNA in machine-learning radiomic models for personalized 5-year malignancy risks per Fukuoka guidelines; and (3) Validating cost-effectiveness in multi-ethnic populations before screening. This repositions GGT as a globally available redox biosignature for PCN early detection, potentially reducing pancreatic cancer burden.