Journal of Gastroenterology and Hepatology最新文献

Adoptive cell therapy (ACT) is a type of immunotherapy in which autologous or allogeneic immune cells, such as tumor-infiltrating lymphocytes or engineered lymphocytes, are infused into patients with cancer to eliminate malignant cells. Recently, autologous T cells modified to express a chimeric antigen receptor (CAR) targeting CD19 showed a positive response in clinical studies for hematologic malignancies and have begun to be used in clinical practice. This article discusses the current status and promise of ACT research in hepatocellular carcinoma (HCC), focusing on challenges in off-the-shelf ACT using primary cells or induced pluripotent stem cells (iPSCs) with or without genetic engineering. Early clinical trials of autologous GPC-3-, MUC1-, or CEA-targeted CAR-T cell therapies are underway for HCC. There is a growing demand for the development of off-the-shelf therapies due to the high cost and manufacturing issues associated with autologous CAR-T. The development of ACT from various cell sources, such as NK cells, NKT cells, macrophages, and γδ T cells without MHC restriction other than T cells has been proposed. Advances in genome editing, including HLA gene knockout to avoid GvHD, and strategies to enhance efficacy in overcoming the suppressive tumor microenvironment, are used to create universal 'off-the-shelf' CAR-T cells which can be used immediately as therapeutic products from healthy donors or iPSC-derived immune cells. Despite several limitations, cell-based immunotherapy is expected to become a key cancer treatment modality for both hematologic malignancies and solid tumors including HCC, thanks to technological advancements overcoming these challenges.

Background: Hepatocellular carcinoma (HCC) and colorectal cancer (CRC) pose a significant threat to human health worldwide, characterized by intricate pathogenesis. A PC-esterase domain containing 1A (PCED1A) is a critical number of the GDSL/SGNH superfamily.

Aim: The aim of this study is to explore the diagnostic value of PCED1A in HCC and CRC and its relationship with immune infiltration.

Methods: The Cancer Genome Atlas (TCGA) database, Gene Expression Omnibus (GEO) database, the Cancer Cell Line Encyclopedia database (CCLE), and the Human Protein Atlas (HPA) were used to detect the expression of PCED1A in tissues and cells. Cibersoft, Timer, and Xcell were used to analyze the effect of PCED1A on immune cell infiltration. The relationship between PCED1A and the immune checkpoint was analyzed. The coexpression analysis of PCED1A was conducted using the LinkedOmics database.

Results: PCED1A was increased in HCC and CRC with poor prognosis. Immunohistochemistry demonstrated that PCED1A was highly expressed in HCC and CRC compared to corresponding normal tissues. PCED1A expression was related to poor overall survival (OS) and progression-free survival (PFS). High PCED1A expression was strongly associated with M2 macrophages, impacting HCC progression. Conversely, low PCED1A expression was closely related to Th2 cells in CRC. In addition, the checkpoint named PDCD1 showed a good correlation with PCED1A high expression group in HCC and CRC. Lastly, the PCED1A and ZNF family showed a complex and intertwined relationship through coexpression analysis on the LinkedOmics database.

Conclusion: PCED1A, related to tumor immune infiltration, is a promising diagnostic biomarker and a valuable therapeutic target for HCC and CRC.

Background/aims: Although incidence and prevalence of inflammatory bowel disease (IBD) have been gradually increasing throughout Asia, incidence of venous thromboembolism (VTE) in Asia is relatively lower than that in Western and is not well known. This study aimed to evaluate incidence of VTE in Asian IBD patients using a systematic review and meta-analysis.

Methods: Studies were identified through literature search of the PubMed, Embase, and Cochrane databases (from inception inclusive April 2024) for English studies. The criteria for selecting participants were as follows: (1) studies including patients with Crohn's disease (CD) and ulcerative colitis in the Asian population; (2) comparisons were specified as with control group of non-IBD patients for comparative incidence; and (3) outcomes were measured by relative risks (RRs) and hazard risk for VTE incidence in nationwide cohort studies. Three independent reviewers extracted published data using standardized procedure in accordance with the reporting guidelines. A fixed-effects model was used to estimate pooled effect sizes. Meta-regression analyses were conducted to identify the potential moderating effects of VTE risk in IBD patients.

Results: Five studies met the inclusion criteria. The pooled RR for overall VTE incidence in Asian IBD patients compared with that in non-IBD patients was 2.065 (95% CI: 1.905-2.238). There was no statistical moderating effect of the variables (mean age, female rate, CD proportion, and country) on the outcomes.

Conclusions: In our study, VTE incidence in Asian IBD patients was higher than that in non-IBD patients. It seemed reasonable to consider prophylaxis for VTE in hospitalized IBD patients.

Endogenous ethanol production, or auto-brewery syndrome (ABS), is a rare condition of the human alimentary canal that results in intoxication without alcohol consumption. Despite its clinical significance, ABS remains largely undiagnosed because of a lack of awareness among clinicians. Published cases have reported extensive biopsychosocial comorbidities accompanying delayed diagnosis and incomplete management; these include social rejection and family separation, court-ordered alcohol rehabilitation and psychiatric admission, legal and employment ramifications, and deteriorating mental health and suicidality. In this mini review, we aim to educate and enlighten clinicians by discussing literature findings pertaining to the pathophysiological mechanisms of gut dysbiosis due to overgrowth of Saccharomyces cerevisiae, E. coli and Klebsiella, impaired intestinal barrier function, and dysregulation of the hypothalamic-pituitary-adrenal axis. Furthermore, we discuss recently discovered associations with sleep quality and mood disorders and explore the medical sequelae of metabolic dysfunction-associated fatty liver disease and metabolic dysfunction-associated steatohepatitis. Drawing on these data, we propose protocols for initial care in the emergency room, subsequent critical care, diagnostic testing with glucose challenge testing, and definitive microbiological testing during the acute phase of illness. We also present an empirical treatment outline while awaiting confirmation of causative organisms and sensitivities.

Background: Gas production due to fermentation from fructose malabsorption (FM) or lactose malabsorption (LM) and small intestinal bacterial overgrowth (SIBO) contribute to the development of gastrointestinal symptoms in patients with irritable bowel syndrome (IBS). However, the impact of the carbohydrate malabsorption, unlike SIBO, is relatively unknown.

Methodology: A multicenter, prospective study of consecutive adults with IBS who underwent a hydrogen breath test (HBT) (glucose, 75 g; lactose, 25 g; or fructose, 25 g) was conducted. The proportion of patients who tested positive for glucose, fructose and lactose HBT were evaluated. The symptom severity, psychology, and quality of life of subjects with SIBO were compared with those having LM and/or FM. Independent factors associated with severe IBS (IBS-symptom severity scale: IBS-SSS > 300) were explored.

Results: A total of 116 subjects were included (median age 56 years, male 35.3%). Of these, 23.3% (27/116), 85.7% (24/28), and 44.4% (16/36) of them tested positive for glucose, lactose, and fructose HBT, respectively. Among those with a positive HBT (n = 65), patients with SIBO were more likely to have the diarrhea-predominant subtype of IBS (77.8% vs. 47.4%, p = 0.014). Severe IBS was associated with SIBO, compared with LM/FM (SIBO: 36.4% vs. LM: 9.1%/FM 13.3%, p = 0.016). With multivariate analysis, SIBO (OR 5.25, p = 0.028) and depression (OR 5.59, p = 0.030) were independently associated with severe IBS.

Conclusion: Although LM and FM commonly co-exist in IBS, their clinical relevance appears to be less significant than that of SIBO. The connection between SIBO with depression reinforces the importance of the microbiome-gut-brain axis in IBS.

Background and aim: This work aims to evaluate the efficacy and safety of free-hand endoscopic full-thickness resection (EFTR) for duodenal subepithelial lesions (SELs).

Methods: We performed a retrospective review of 105 patients with duodenal SELs who underwent free-hand EFTR. Free-hand EFTR means no other devices (over-the-scope clip or full-thickness resection device) are required. The preoperative baseline data, procedure-related characteristics, and postoperative outcomes were analyzed.

Results: The technical success rate was 99.0%, and the en bloc resection rate was 94.2%. A total of nine (8.7%) patients experienced major postoperative adverse events (AEs). The incidence of major AEs was significantly higher for lesions with a maximum diameter ≥ 2 cm (30.4%) than for lesions with a maximum diameter < 2 cm (2.6%) (p < 0.001). There were also significant differences in the incidence of major AEs for peri-ampullary lesions (37.5%), bulb lesions (4.8%), bulb-descending junction lesions (6.7%), and descending part lesions (12.5%) (p = 0.032). Multivariable regression analyses revealed that the maximum diameter ≥ 2 cm (OR = 18.108; 95% CI = 1.881-174.281; p = 0.012) and lesions located in peri-ampullary (OR = 18.950; 95% CI = 1.219-294.648; p = 0.036) were independent risk factors for major AEs. The mean duration of the follow-up period was 36.6 ± 21.3 months, and only one patient with gastrointestinal stromal tumors recurred.

Conclusions: Free-hand EFTR is a safe and effective technique for nonampullary duodenal SELs with a maximum diameter of < 2 cm. Given the complexity of the duodenal anatomy, this procedure should be performed by experienced endoscopists.

Background and aim: To assess the relationship between survival outcomes and subtypes of radiological progressive disease (PD) in patients with hepatocellular carcinoma (HCC) treated with atezolizumab and bevacizumab (Atezo/Bev).

Methods: A total of 462 patients with Atezo/Bev-treated HCC diagnosed with radiological PD during follow-up were enrolled. PD was classified into three categories: progression or emergence of intrahepatic lesions (PD-IH), macroscopic vascular invasion (PD-MVI), and extrahepatic spread lesions (PD-EHS). We defined PD-multiple as the presence of two or more PD categories. Subsequent analysis was categorized into the "PD-IH or PD-EHS" and "PD-MVI or PD-multiple" groups.

Results: The median progression-free survival (PFS) durations for patients with PD-IH, PD-MVI, PD-EHS, and PD-multiple were 5.3, 3.2, 3.9, and 3.5 months (p = 0.003). Patients with "PD-IH or PD-EHS" and "PD-MVI or PD-multiple" had median PFS of 5.2 and 3.5 months (p < 0.001). Median overall survival (OS) for PD-IH, PD-MVI, PD-EHS, and PD-multiple was 22.3, 15.1, 19.4, and 14.2 months (p = 0.002). The OS for patients with "PD-IH or PD-EHS" and "PD-MVI or PD-multiple" was 21.4 and 14.5 months (p < 0.001). Multivariate analysis demonstrated that ECOG-PS ≥ 1 (hazard ratio (HR), 1.508), α-fetoprotein levels ≥ 100 ng/mL (HR, 1.293), albumin-bilirubin grade ≥ 2 (HR, 1.573), liver cirrhosis (HR, 1.361), and PD subtypes PD-MVI or PD-multiple (HR, 1.735) were independently associated with OS.

Conclusions: Patients with HCC undergoing Atezo/Bev treatment, diagnosed with PD-multiple (not solely based on IH or EHS) or PD-MVI, experienced poor prognosis, specifically in terms of OS.

Background: Similar worsening epidemics globally have been showed in newly coined metabolic dysfunction-associated steatotic liver disease (MASLD) and inflammatory bowel disease (IBD). We aimed to investigate the prospective association of MASLD, MASLD types, and cardiometabolic risk factors (CMRFs) with long-term risk of incident IBD in a large-scale population cohort.

Methods: Participants free of IBD at enrollment from UK Biobank were included. Baseline MASLD was measured by fatty liver index together with at least one CMRF, based on the latest AASLD/EASL criteria. MASLD type was classified as pure MASLD and MetALD (MASLD with increased alcohol intake). Primary outcome was incident IBD, including ulcerative colitis (UC) and Crohn's disease (CD). Multivariable Cox regression was conducted to examine the related associations.

Results: Overall, 403 520 participants (aged 56.2 ± 8.1 years, 45.6% males) were included. Of whom, 151 578 (37.6%) were considered as MASLD at baseline. During a median of 13.0 years' follow-up, 2398 IBD cases were identified. Compared with normal population, individuals with MASLD showed significant higher associations of incident IBD (HR = 1.39, 95% CI: 1.21-1.60), UC (HR = 1.34, 95% CI: 1.13-1.58), and CD (HR = 1.51, 95% CI: 1.20-1.89). Meanwhile, results were consistent when assessing pure MASLD (HR = 1.43, 95% CI: 1.23-1.66) and MetALD (HR = 1.46, 95% CI: 1.15-1.86). The excess risk of incident IBD was more evident with the increase of CMRFs numbers (p_trend < 0.001).

Conclusion: MASLD, either pure MASLD or MetALD, and a combination of different CMRFs are all associated with increased risk of IBD, including both UC and CD. Additionally, there is greater risk of incident IBD as the number of CMRFs increase.