Helicobacter pylori infection exacerbates metabolic dysfunction-associated steatotic liver disease through lipid metabolic pathways: a transcriptomic study.

BACKGROUND: The relationship between Helicobacter pylori (H. pylori) infection and metabolic dysfunction-associated steatotic liver disease (MASLD) has attracted increased clinical attention. However, most of those current studies involve cross-sectional studies and meta-analyses, and experimental mechanistic exploration still needs to be improved. This study aimed to investigate the mechanisms by which H. pylori impacts MASLD. METHODS: We established two H. pylori-infected (Cag A positive and Cag A negative) mouse models with 16 weeks of chow diet (CD) or high-fat diet (HFD) feeding. Body weight, liver triglyceride, blood glucose, serum biochemical parameters, inflammatory factors, and insulin resistance were measured, and histological analysis of liver tissues was performed. Mouse livers were subjected to transcriptome RNA sequencing analysis. RESULTS: Although H. pylori infection could not significantly affect serum inflammatory factor levels and serum biochemical parameters in mice, serum insulin and homeostatic model assessment for insulin resistance levels increased in CD mode. In contrast, H. pylori Cag A + infection significantly aggravated hepatic pathological steatosis induced by HFD and elevated serum inflammatory factors and lipid metabolism parameters. Hepatic transcriptomic analysis in the CD groups revealed 767 differentially expressed genes (DEGs) in the H. pylori Cag A + infected group and 1473 DEGs in the H. pylori Cag A- infected group, and the "nonalcoholic fatty liver disease" pathway was significantly enriched in KEGG analysis. There were 578 DEGs in H. pylori Cag A + infection combined with the HFD feeding group and 820 DEGs in the H. pylori Cag A- infected group. DEGs in the HFD groups were significantly enriched in "fatty acid degradation" and "PPAR pathway." Exploring the effect of different Cag A statuses on mouse liver revealed that fatty acid binding protein 5 was differentially expressed in Cag A- H. pylori. DEG enrichment pathways were concentrated in the "PPAR pathway" and "fatty acid degradation." CONCLUSIONS: Clinicians are expected to comprehend the impact of H. pylori on MASLD and better understand and manage MASLD. H. pylori infection may exacerbate the development of MASLD by regulating hepatic lipid metabolism, and the H. pylori virulence factor Cag A plays a vital role in this regulation.

Safety and efficacy of ESD for laterally spreading tumors with hemorrhoids close to the dentate line.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a curative treatment for laterally spreading tumors (LSTs). However, the outcomes of ESD for LSTs with hemorrhoids remain largely unknown. Our study aimed to evaluate the usefulness of ESD in managing LSTs with hemorrhoids. MATERIAL AND METHODS: We retrospectively collected 418 consecutive LST patients treated with ESD between 2011 and 2023. A retrospective comparative analysis was conducted. RESULTS: There were 85 patients included in the hemorrhoids group and 333 patients included in the other group. The en-bloc resection rate, R0 resection rate, and curative resection rate were comparable in these two groups (p > 0.05). The LSTs with hemorrhoids have a significantly higher intraoperative bleeding rate during ESD when compared to the other group (12.9% vs. 5.4%, p = 0.028). Rates of intraoperative perforation and anal pain in the hemorrhoid group were significantly higher than those in the no-hemorrhoid group (2.4% vs. 0%, p = 0.041; 9.4% vs.0.6%, p < 0.001; respectively). Moreover, most of the related manifestations caused by hemorrhoids were relieved to various degrees after ESD. CONCLUSIONS: ESD is a safe and effective treatment strategy for LSTs with hemorrhoids. A multi-center and prospective study should be conducted in the future to validate our results.

Endoscopic submucosal dissection for giant colorectal laterally spreading tumor 33 cm in diameter.

A 77-year-old male presented with recurrent diarrhea for more than 2 years, aggravated and a 1-month history of a rectal mass. High-definition white light colonoscopy showed an approximately circumferential elevated lesion from about 12 cm from the anus to the dentate line, with surface nodules of different sizes, some surfaces slightly congested, and internal hemorrhoids. The patient was diagnosed with a giant laterally spreading tumor-granular nodular mixed type (LST-G-M) of the rectum with the possibility of local malignant transformation and treated with single-tunnel assisted endoscopic submucosal dissection (ESD) at the patient's request. Histopathology of the specimen showed villous tubular adenoma with local carcinogenesis, 33*12cm in size, negative margins, no lymphovascular invasion. No bleeding or perforation was observed during or after procedure, and no stenosis was scrutinized at 2 months later.

M2 macrophages participate in ILC2 activation induced by Helicobacter pylori infection.

Helicobacter pylori (H. pylori) causes a diversity of gastric diseases. The host immune response evoked by H. pylori infection is complicated and can influence the development and progression of diseases. We have reported that the Group 2 innate lymphocytes (ILC2) were promoted and took part in building type-2 immunity in H. pylori infection-related gastric diseases. Therefore, in the present study, we aim to clarify how H. pylori infection induces the activation of ILC2. It was found that macrophages were necessary for activating ILC2 in H. pylori infection. Mechanistically, H. pylori infection up-regulated the expression of indoleamine 2,3-dioxygenase (IDO) in macrophages to induce M2 polarization, and the latter secreted the alarmin cytokine Thymic Stromal Lymphopoietin (TSLP) to arouse ILC2.

The feasibility of endoscopic resection for colorectal laterally spreading tumors.

The present study aimed to investigate the feasibility and safety of endoscopic resection for colorectal laterally spreading tumors (LSTs) in different size groups. This retrospective study included 2699 patients with LSTs who underwent endoscopic treatment at the Second Xiangya Hospital of Central South University from May 2012 to February 2022. The patient baseline and procedure outcomes were compared between the < 5 cm group, 5-10 cm group, and ≥ 10 cm group. Meanwhile, lesions larger than 5 cm in diameter were longitudinally compared for endoscopic safety using ESD with surgical operation outcomes. There were 2105 patients in the < 5 cm group, 547 patients in the 5-10 cm group, and 47 patients in the ≥ 10 cm group. En bloc resection and R0 resection rates, the incidence of adverse events, length of stay (LOS), and medical costs significantly differed between the groups (P < 0.01). Comorbidity of diabetes or hypertension, history of antithrombotic drug use, lesion size, location, gross type, endoscopic procedures selection, and circumferential extent of the mucosal defect were independent risk factors for delayed bleeding (P < 0.05). En bloc resection, R0 resection, and lesion canceration were associated with local recurrence. For lesions larger than 5 cm in diameter, ESD had similar R0 resection and local recurrence rates compared with a surgical operation but a lower en bloc rate, LOS, and medical costs. Expert endoscopists can significantly increase en bloc and R0 resection rates and reduce the incidence of adverse events. Endoscopic resection results distinguish in different size groups of colorectal LSTs, yet its safety and feasibility are not inferior to a surgical operation.

An update: is there a relationship between H. pylori infection and nonalcoholic fatty liver disease? why is this subject of interest?

Helicobacter pylori (H. pylori) infection is thought to impact various extragastric diseases, including nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease. Meanwhile, the pathogenesis of NAFLD needs further research, and effective treatment for this disease remains elusive. In this mini-review, we enumerate and ponder on the evidence demonstrating an association between H. pylori infection and NAFLD. Primarily, we delve into high-quality meta-analyses and clinical randomized controlled trials focusing on the association studies between the two. We also discuss clinical studies that present opposite conclusions. In addition, we propose a mechanism through which H. pylori infection aggravates NAFLD: inflammatory cytokines and adipocytokines, insulin resistance, lipid metabolism, intestinal barrier and microbiota, H. pylori outer membrane vesicles and H. pylori-infected cell-extracellular vesicles. This mini-review aims to further explore NAFLD pathogenesis and extragastric disease mechanisms caused by H. pylori infection.