World Journal of Gastroenterology最新文献

Background: C-X-C chemokine receptor type 5 (CXCR5)⁺CD8⁺ T cells represent a unique immune subset with dual roles, functioning as cytotoxic cells in persistent viral infections while promoting B cell responses. Despite their importance, the specific role of CXCR5⁺CD8⁺ T cells in chronic hepatitis B (CHB), particularly during interferon-alpha (IFN-α) treatment, is not fully understood. This study aims to elucidate the relationship between CXCR5⁺CD8⁺ T cells and sustained serologic response (SR) in patients undergoing 48 weeks of pegylated IFN-α (peg-IFN-α) treatment for CHB.

Aim: To elucidate the relationship between CXCR5⁺CD8⁺ T cells and sustained SR in patients undergoing 48 weeks of peg-IFN-α treatment for CHB.

Methods: This study enrolled 60 patients with hepatitis Be antigen (HBeAg)-positive CHB undergoing 48 weeks of peg-IFN-α treatment. Participants were assessed for eligibility based on criteria such as persistent HBsAg-positive status for at least six months, HBeAb-negative, hepatitis B virus DNA levels exceeding 2 × 10⁴ copies/mL, and alanine aminotransferase (ALT) levels between 2 and 10 times the upper limit of normal. Blood samples were collected at baseline and at weeks 12, 24, 48, and a 24-week treatment-free follow-up (week 72) to measure serum interleukin (IL)-21 concentration via ELISA and to analyze CXCR5 and programmed death-ligand 1 (PD-L1) expression on CD8⁺ T cells by flow cytometry, CXCR5 is a chemokine receptor that directs immune cells to specific tissues, while PD-L1 is a protein that regulates immune responses by inhibiting T cell activity.

Results: Patients with CHB exhibited significantly lower levels of circulating CXCR5⁺CD8⁺ T cells compared to healthy controls (P < 0.01). Notably, CXCR5+CD8+ T cells were prominently expressed in patients who achieved sustained SR compared to non-SR (NSR). A significant correlation was observed between CXCR5 and PD-L1 expression (r = -0.189, P = 0.002). However, there was no significant correlation between serum IL-21 levels and CXCR5⁺CD8⁺ lymphocytes (r = -0.03, P = 0.625) or serum ALT levels (r = 0.026, P = 0.678).

Conclusion: The enhanced expression of CXCR5⁺CD8⁺ T cells in patients achieving HBeAg seroconversion during IFN-α treatment suggests that these cells play a crucial role in antiviral immune responses against hepatitis B. This study highlights the potential of CXCR5⁺CD8⁺ T cells as immune regulators in CHB, which may inform future therapeutic strategies to optimize antiviral treatments.

In this article, we provide commentary on the recent article by Zhao et al. We focus on the shifts in the gut microbiota of patients with hepatitis B virus (HBV)-associated cirrhosis/portal hypertension (PH) following transjugular intrahepatic portosystemic shunt (TIPS) and the implications for understanding the mechanisms, diagnosis, and treatment. By comparing the gut microbiota composition and dynamic changes before and after TIPS in patients with and without hepatic encephalopathy, the authors found an increase in non-probiotic bacteria in those who developed hepatic encephalopathy post-TIPS, with Morganella species present only in the hepatic encephalopathy group. The gut microbiota changes post-TIPS among patients without the occurrence of hepatic encephalopathy suggest potential therapeutic benefits through prophylactic microbiome therapies. Furthermore, the specific gut microbiota alterations may hold promise to predict the risk of hepatic encephalopathy in individuals undergoing TIPS for HBV-related PH. Despite these promising findings, future studies are needed to address limitations, including a small sample size, a relatively short evaluation period for gut microbiota alterations, the absence of data on dynamic alterations in gut microbiota post-TIPS and their correlation with blood ammonia levels, and the lack of validation in animal models. In conclusion, Zhao et al's study has shed new light on the link of gut microbiota with post-TIPS hepatic encephalopathy, potentially through the intricate gut-liver axis, and has important clinical implications for improving the management of patients with HBV-related PH.

Helicobacter pylori-associated gastritis (HPAG) is a common condition of the gastrointestinal tract. However, extensive and long-term antibiotic use has resulted in numerous adverse effects, including increased resistance, gastrointestinal dysfunction, and increased recurrence rates. When these concerns develop, traditional Chinese medicine (TCM) may have advantages. TCM is based on the concept of completeness and aims to eliminate pathogens and strengthen the body. It has the potential to prevent this condition while also boosting the rate of Helicobacter pylori eradication. This review elaborates on the mechanism of TCM treatment for HPAG based on cellular signalling pathways, which reflects the flexibility of TCM in treating diseases and the advantages of multi-level, multi-pathway, and multi-target treatments for HPAG.

This article discusses the recent study written by Koizumi et al. Alcohol-associated liver disease (ALD) is a major cause of liver-related morbidity and mortality, which is driven by complex mechanisms, including lipid accumulation, apoptosis, and inflammatory responses exacerbated by gut barrier dysfunction. The study explored the therapeutic potential of elafibranor, a dual peroxisome proliferator-activated receptor alpha/delta agonist. In clinical trials, elafibranor has shown promise for the treatment of other liver conditions; however, its effects on ALD remain unclear. The authors' findings indicate that elafibranor significantly reduced liver fibrosis and enhanced gut barrier integrity in patients with ALD. These positive effects of elafibranor are mediated through multiple pathways. Elafibranor promotes lipid metabolism, reduces oxidative stress, and inhibits inflammatory responses by restoring gut barrier function. Specifically, it improves hepatocyte function by enhancing autophagic and antioxidant capacity, and it mitigates inflammation by suppressing the lipopolysaccharide/toll-like receptor 4/nuclear factor kappa B signaling pathway. These findings indicate that elafibranor has promising clinical applications. In addition, the study highlights elafibranor's potential as a therapeutic agent for liver diseases, particularly ALD. This article underscores the importance of understanding the mechanistic pathways underlying ALD and suggests directions for future research aimed at elucidating the benefits and limitations of elafibranor.

Hepatocellular carcinoma is one of the leading causes of cancer-related deaths globally, and effective treatments are urgently needed. The present study aimed to investigate the inhibitory effect of Calculus Bovis (CB) on liver cancer and the underlying mechanisms. CB inhibited M2 tumor-associated macrophage polarization and modulated the Wnt/β-catenin signaling pathway, thereby suppressing the proliferation of liver cancer cells. The inhibitory effect on liver cancer growth was confirmed by both in vivo and in vitro experiments (detailed by Huang et al). The present study provides a theoretical basis for the application of CB for the treatment of liver cancer, providing new avenues for liver cancer treatment.

Background: Patients with hepatitis B virus (HBV) infection require chronic and personalized care to improve outcomes. Large language models (LLMs) can potentially provide medical information for patients.

Aim: To examine the performance of three LLMs, ChatGPT-3.5, ChatGPT-4.0, and Google Gemini, in answering HBV-related questions.

Methods: LLMs' responses to HBV-related questions were independently graded by two medical professionals using a four-point accuracy scale, and disagreements were resolved by a third reviewer. Each question was run three times using three LLMs. Readability was assessed via the Gunning Fog index and Flesch-Kincaid grade level.

Results: Overall, all three LLM chatbots achieved high average accuracy scores for subjective questions (ChatGPT-3.5: 3.50; ChatGPT-4.0: 3.69; Google Gemini: 3.53, out of a maximum score of 4). With respect to objective questions, ChatGPT-4.0 achieved an 80.8% accuracy rate, compared with 62.9% for ChatGPT-3.5 and 73.1% for Google Gemini. Across the six domains, ChatGPT-4.0 performed better in terms of diagnosis, whereas Google Gemini demonstrated excellent clinical manifestations. Notably, in the readability analysis, the mean Gunning Fog index and Flesch-Kincaid grade level scores of the three LLM chatbots were significantly higher than the standard level eight, far exceeding the reading level of the normal population.

Conclusion: Our results highlight the potential of LLMs, especially ChatGPT-4.0, for delivering responses to HBV-related questions. LLMs may be an adjunctive informational tool for patients and physicians to improve outcomes. Nevertheless, current LLMs should not replace personalized treatment recommendations from physicians in the management of HBV infection.

Background: Minimally invasive esophagectomy (MIE) is a widely accepted treatment for esophageal cancer, yet it is associated with a significant risk of surgical adverse events (SAEs), which can compromise patient recovery and long-term survival. Accurate preoperative identification of high-risk patients is critical for improving outcomes.

Aim: To establish and validate a risk prediction and stratification model for the risk of SAEs in patients with MIE.

Methods: This retrospective study included 747 patients who underwent MIE at two centers from January 2019 to February 2024. Patients were separated into a train set (n = 549) and a validation set (n = 198). After screening by least absolute shrinkage and selection operator regression, multivariate logistic regression analyzed clinical and intraoperative variables to identify independent risk factors for SAEs. A risk stratification model was constructed and validated to predict the probability of SAEs.

Results: SAEs occurred in 10.2% of patients in train set and 13.6% in the validation set. Patients with SAE had significantly higher complication rate and a longer hospital stay after surgery. The key independent risk factors identified included chronic obstructive pulmonary disease, a history of alcohol consumption, low forced expiratory volume in the first second, and low albumin levels. The stratification model has excellent prediction accuracy, with an area under the curve of 0.889 for the training set and an area under the curve of 0.793 for the validation set.

Conclusion: The developed risk stratification model effectively predicts the risk of SAEs in patients undergoing MIE, facilitating targeted preoperative interventions and improving perioperative management.

Prognostication of compensated advanced chronic liver disease (cACLD) is of paramount importance for the physician-and-patient communication and for rational clinical decisions. The paper published by Dallio et al reports on red cell distribution width (RDW)/platelet ratio (RPR) as a non-invasive biomarker in predicting decompensation of metabolic dysfunction-associated steatotic liver disease (MASLD)-related cACLD. Differently from other biomarkers and algorithms, RPR is inexpensive and widely available, based on parameters which are included in a complete blood count. RPR is computed on the grounds of two different items, one of which, RDW, mirrors the host's response to a variety of disease stimuli and is non-specific. The second parameter involved in RPR, platelet count, is more specific and has been used in the hepatological clinic to discriminate cirrhotic from non-cirrhotic chronic liver disease for decades. Cardiovascular disease is the primary cause of mortality among MASLD subjects, followed by extra-hepatic cancers and liver-related mortality. Therefore, MASLD biomarkers should be validated not only in terms of liver-related events but also in the prediction of major adverse cardiovascular events and cardiovascular mortality and extra-hepatic cancers. Adequately sized multi-ethnic confirmatory investigation is required to define the role and significance of RPR in the stratification of MASLD-cACLD.

Liver cancer, and in particular hepatocellular carcinoma (HCC) is a disease of rising prevalence and incidence. To date, definitive treatment options include either surgical excision or ablation of the affected area. With increasing research on several pathways that could be involved in the progression of HCC, new elements within these pathways emerge as potential targets for novel therapies. The WNT/β-catenin pathway favors the presence of M2 tumor-associated macrophages which in turn promote tumor growth and metastasis. The inhibition of this pathway is considered a good candidate for such targeted therapeutic interventions. Interestingly, as Huang et al show in their recently published article, Calculus bovis which is used in traditional Chinese medicine can exert an inhibitory effect on the β-catenin pathway and become a potential candidate for targeted pharmacotherapy against liver cancer.

This letter critically evaluates Jiang et al's article on the differentiation of benign and malignant liver lesions using Emax and platelet count. Despite notable findings, significant methodological and interpretative limitations are identified. The study lacks detailed assay conditions for Emax measurement, employs inadequate statistical methods without robust multivariate analysis, and does not provide clinically relevant threshold values. The nomogram's reliance on Emax as a major diagnostic contributor is questionable due to attenuation in hepatocellular carcinoma patients with cirrhosis. Moreover, the study's limitations, such as selection bias and confounding factors, are not adequately addressed. Future research should adopt more rigorous methodologies, including prospective studies with larger cohorts and standardized protocols for biomarker measurement, to enhance validity and clinical applicability.