eGastroenterology最新文献

This review aims to provide a comprehensive overview of the existing therapeutic options for managing neuropathic and/or cardiac manifestations associated with transthyretin amyloidosis (ATTR), along with investigational therapeutic candidates under evaluation in ongoing clinical trials. Additionally, emerging approaches for combating this life-threatening disease are discussed. Recent advancements in non-invasive diagnostic techniques for the detection of ATTR have facilitated improved diagnosis and identification at an earlier disease stage, thereby enhancing the potential efficacy of therapeutic interventions. Presently, there exists a range of clinically available treatments targeting ATTR, alongside investigational agents undergoing assessment in clinical trials. Therapeutic modalities encompass tetramer stabilisation, gene silencing, and ATTR fibril disruption and removal strategies. Historically, ATTR has been underdiagnosed. However, with the progression of diagnostic methodologies and the introduction of disease-modifying treatments, early diagnosis and initiation of treatment have significantly transformed the management of this condition, and effective treatment modalities have been introduced and are under development.

Background: To investigate the correlation between infection of Helicobacter pylori (H. pylori) and the risk of reflux oesophagitis (RE) occurrence or recurrence.

Methods: Literature was retrieved from PubMed, Embase, Web of Science and Cochrane Library databases, and the search period ranged from the time of database establishment to December 2024. Prospective cohort studies and randomised controlled trials were included for data analysis to assess the association of infection of H. pylori with the risk of RE occurrence and recurrence, and subgroup analyses were performed.

Results: The overall risk of RE in the H. pylori-eradicated group was significantly higher than that in the placebo group (p<0.01). The analysis failed to detect a statistically significant difference in RE risk between the H. pylori-eradicated group and placebo group among different age groups, regions and disease types. The risk of RE significantly increased after eradication of H. pylori for >1 year (p<0.01).

Conclusion: Infection of H. pylori in different age groups, regions and diseases may lead to the occurrence or recurrence of RE after receiving H. pylori eradication treatment. This correlation increased as the follow-up period extended. Although receiving H. pylori eradication treatment may increase the risk of RE occurrence or recurrence, doctors should take into consideration the individual situation of the patient to determine whether eradication treatment should be administered concomitantly or postponed during clinical treatment decision making.

Prospero registration number: CRD 42024529321.

The new European clinical practice guidelines from three scientific societies (European Association for the Study of the Liver, European Association for the Study of Diabetes and European Association for the Study of Obesity) on the management of metabolic dysfunction-associated steatotic liver disease (MASLD) provide detailed recommendations on diagnosis, risk stratification, monitoring strategies, treatment and prevention. Lifestyle interventions (eg, weight reduction, Mediterranean diet, exercise, alcohol abstinence) and the treatment of cardiometabolic risk factors continue to be the mainstay of treatment and prevention of the disease. Incretin mimetics that are approved to treat obesity and/or type 2 diabetes such as semaglutide and tirzepatide have benefits for ameliorating metabolic dysfunction-associated steatohepatitis (MASH). Novel developments include adapted strategies for screening (case finding) using non-invasive tests (NITs) with a focus on detecting fibrosis or cirrhosis, risk-adjusted monitoring of MASLD by NITs as well as the recommendation to use, if locally approved, the thyroid hormone receptor β-agonist resmetirom in patients with non-cirrhotic MASH fibrosis (≥F2 stage).

Background: Dietary variation has been identified as a key contributor to microbiome diversification. However, assessing its true impact in a cross-sectional setting is complicated by biological confounders and methodological hurdles. We aimed to estimate the impact of a reduction of dietary variation (dietary convergence) on faecal microbiota composition among individuals consuming a Western-type diet.

Methods: 18 healthy volunteers recruited in the region of Flanders (Belgium) were followed up for 21 days. Participants were allowed to consume their habitual diet during a baseline and follow-up period (7 and 8 days, respectively), intersected by a 6-day intervention during which dietary options were restricted to oat flakes, whole milk and still water. Faecal samples were collected on a daily basis. Quantitative microbiome profiles were constructed, combining 16S rRNA gene amplicon sequencing with flow cytometry cell counting. Blood samples were taken at the beginning and end of each study week.

Results: While the intervention did not affect transit time (as assessed through the analysis of stool moisture), consumption of the restricted diet resulted in an increased prevalence of the Bacteroides2 microbiome community type. Microbial load and Faecalibacterium abundance decreased markedly. Despite dietary restrictions, no convergence of microbial communities (reduction of interindividual and intraindividual variation) was observed. The effect size (ES) of the intervention on genus-level microbiome community differentiation was estimated as 3.4%, but substantial interindividual variation was observed (1.67%-16.42%).

Conclusion: The impact of dietary variation on microbiome composition in a Western population is significant but limited in ES, with notable individual exceptions. Dietary convergence does not invariably translate into interindividual convergence of faecal microbial communities.

Hepatocellular carcinoma (HCC) typically develops in the context of chronic liver disease, where prolonged hepatocyte exposure to inflammation drives the synergistic accumulation of genetic and epigenetic alterations. Epigenetic regulation encompasses multiple mechanisms that govern the transcription machinery accessibility to DNA. This process is regulated by the addition and removal of covalent marks on chromatin, which can either affect DNA-histone interactions or serve as scaffolds for other proteins, among other mechanisms. Recent research has revealed that epigenetic alterations can disrupt chromatin homeostasis, redirecting transcriptional regulation to favour cancer-promoting states. Consequently, these alterations play a pivotal role in the acquisition of cancer hallmarks and provide insights into several biological processes involved in hepatocarcinogenesis. This review highlights the key epigenetic mechanisms underlying the development, progression and dissemination of HCC, with a particular focus on DNA methylation and histone post-translational modifications. This knowledge is relevant for guiding the development of innovative therapeutic approaches based on epigenetic modulators.

Background: Severe alcohol-associated hepatitis (sAH) is a life-threatening condition with high mortality, where corticosteroid use is the only treatment that has shown short-term benefits. Pentoxifylline, an anti-tumour necrosis factor-alpha agent, has been proposed for its potential to improve outcomes, especially in patients with acute kidney injury (AKI). We aimed to evaluate the impact of pentoxifylline on mortality in patients with sAH and AKI in a well-characterised global cohort.

Methods: We conducted a retrospective, registry-based study including patients meeting the National Institute on Alcohol Abuse and Alcoholism clinical criteria for sAH and AKI. Mortality was the primary endpoint, with liver transplantation as a competing risk. Statistical analysis included Cox regression and Kaplan-Meier survival estimates.

Results: We included 525 patients from 20 centres across eight countries. The median age was 48 years, with 26.1% females, and 76.9% had a history of cirrhosis. Multivariable Cox regression models showed that pentoxifylline use was not associated with survival (HR 1.20, 95% CI 0.85 to 1.69, p=0.291). Factors associated with mortality included age (HR 1.23, 95% CI 1.10 to 1.36, p<0.001), Model for End-Stage Liver Disease score at admission (HR 1.06, 95% CI 1.04 to 1.08, p<0.001) and renal replacement therapy use (HR 1.39, 95% CI 1.05 to 1.84, p=0.019). The main causes of death were multiple organ failure (42%), infections (10%), oesophageal varices bleeding (7%) and renal failure (6%).

Conclusion: Pentoxifylline showed no significant benefit on mortality in patients with sAH and AKI. Further studies are needed to refine treatment strategies for this high-risk group.

Background: Healthy livers contain a large number of resident macrophages named Kupffer cells (KCs), which are partially replaced by infiltrating monocyte-derived macrophages (MoMFs) during acute or chronic liver injury. Despite extensive research, understanding macrophage heterogeneity, spatial distribution and interactions with other cells within the liver remains challenging.

Methods: This study employs sequential multiplex immunofluorescence staining, advanced image analysis and single-cell RNA sequencing (scRNA-seq) analysis to characterise macrophages in both healthy and diseased livers in mice.

Results: Our data revealed that liver KCs made up more than 80% of total immune cells in healthy mouse livers, while massive amounts of MoMFs infiltrated into the livers after acute and chronic liver injury. KCs were more abundant and larger in Zones 1 and 2 compared with Zone 3 in healthy livers. Zone 1 KCs exhibited higher phagocytic activity than Zone 2/3 KCs and MoMFs. We simultaneously evaluated cell proliferation and apoptosis on one slide and found that proliferation and apoptosis of KCs and MoMFs significantly increased in acutely injured livers. We also performed scRNA-seq to investigate liver macrophage gene expression in naïve and concanavalin A (ConA)-treated mice. MoMF clusters expanded following ConA treatment, while KCs remained stable. Macrophages were divided into distinct subtypes, including C1q⁺ MoMFs, with differential expression of genes like Trem2, Spp1, Fabp5 and Gpnmb. Newly recruited C1q^- MoMFs expressed high levels of Lyz and Ccr2, while Itgax (Cd11c)⁺ MoMFs expressed endothelin converting enzyme 1 (Ece1), a gene encoding ECE1 enzyme that activates endothelin to promote hepatic stellate cell contraction and necrotic lesion resolution. By immunostaining analysis of the proteins encoded by these signature genes, we identified several populations of MoMFs that were mainly located surrounding the necrotic lesion area and expressed various proteins that are involved in dead cell debris clearance.

Conclusion: We developed a robust framework for studying liver macrophages in vivo, offering insights into their roles in host defence and liver injury/repair. We identified several populations of MoMFs that surround necrotic lesion areas and express proteins that promote dead cell debris clearance. These necrotic lesion-associated macrophages likely play key roles in promoting necrotic lesion resolution.