Translational gastroenterology and hepatology最新文献

Background: Obesity, meaning an overweight problem, can be considered an epidemic disease that is strongly related to non-alcoholic fatty liver disease (NAFLD). Clinical studies indicate that the consumption of probiotics and prebiotics modulates the intestinal microbiota, promoting weight loss, decreasing adipose tissue and proinflammatory factors. The aim of the study was to analyze the response of the liver (transcriptomic and histology) to a dietary supplementation with probiotics and prebiotics of a murine model.

Methods: We evaluated the liver transcriptome using an obese murine model (C57BLACK6) by inducing obesity with a high-fat diet for 8 weeks followed by synbiotic supplements in a normocaloric diet for another 8 weeks. Pool screening analysis (5 samples) was completed using a synthesis of cDNA. The transcriptome was analyzed by DNA microarrays hybridizing on 22,000 mouse genes. Differentially expressed genes (DEGs) were analyzed under 3 hybridization processes with the aid of GenArise software using the z-score value. As a result of transcriptome analysis, fatty acid-binding genes (Cyp7a1 and Acox2) were selected to analyze the liver response, molecular and histologically.

Results: The transcriptome analysis results indicate 1.26% overexpression and a 2.2% average repression in relation to the hybridized genome; DEGs allow us to identify genes associated with fatty acid metabolism. The synbiotic treatment increases the expression of Cyp7a1 and Acox2 significantly (P<0.05) in correlation with a decrease in the histological level of accumulated fat in the tissue.

Conclusions: The synbiotic could be an adjuvant treatment to obesity and NAFLD as it can increase the production of bile acids coming from the classical pathway which promotes the absorption of ectopically accumulated lipids thus reducing the development of NAFLD at histological and molecular level.

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Background: To date, there is no consensus classification of post-liver transplantation biliary strictures (LTBS), particularly for guiding treatment. This study aimed to propose a novel classification system for guiding treatment choice and prognosis prediction.

Methods: Patients with biliary stricture (BS) from three centers were analyzed retrospectively. Combined with the latest guidelines, a location-based classification system was developed that included the following categories: extrahepatic BS (type I), perihilar BS (type II), and intrahepatic BS (type III). Stent treatment choices were assessed, and a fully covered self-expandable metal stent (FCMS) with plastic biliary stent (PBS) implantation method for type II was introduced. Treatment characteristics and outcomes among the three types were also analyzed.

Results: According to initial successful endoscopic cholangiography, 96 patients were classified into three types: I (43.8%), II (32.3%) and III (24.0%). For type I patients, fewer treatment sessions (P=0.02) and lower costs (P=0.04) were noted for FCMS compared to PBS. Compared to PBS implantation alone, FCMS + PBS had a similar advantage as the type II group. During the follow-up period, 69.0% of type I, 61.3% of type II and 34.7% of type III patients achieved stent-free success, and type III patients demonstrated the worst treatment effects (P=0.03). The stent duration, number of endoscopic procedures increased from type I to type III patients (P=0.04).

Conclusions: This location-based classification provides insights for clinical treatment recommendations, offering a typological basis for establishing a standardized treatment protocol for BS after liver transplantation.

Background: Crohn's disease (CD) is a chronic inflammatory condition requiring regular follow-up through consultations and monitoring via laboratory, radiographic, and endoscopic examinations. Fecal calprotectin (FC) and magnetic resonance (MR) enterography are prominent non-invasive methods for assessing disease activity. However, while MR enterography is a valuable diagnostic tool, its high cost and limited accessibility present challenges for widespread use. In contrast, FC is a more affordable and accessible biomarker. To perform a systematic review (SR) examining the correlation between FC levels and MR enterography findings in patients with ileal CD.

Methods: A systematic literature search was conducted across the following databases: PubMed, PubMed PMC, BVS-BIREME, SCOPUS, Web of Science, EMBASE, and Cochrane Library, and it was completed in October 2024.

Results: Eight studies were included in this SR. Seven demonstrated a positive correlation between FC levels and MR enterography findings. Additionally, two studies reported significantly lower FC levels in ileal CD than in exclusive colonic or ileocolonic CD cases. The FC cutoff values ranged from >100 to >430 µg/g of feces to determine the activity of the disease.

Conclusions: FC proved to be a reliable biomarker for diagnosing and monitoring CD, demonstrating a positive correlation with findings from MR enterography.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasing global health concern associated with metabolic syndromes such as obesity and type 2 diabetes. While statins are widely used to manage hypercholesterolemia, their potential protective effects against liver-related outcomes in MASLD have not been thoroughly explored. This study aims to evaluate the prognostic impact of statin use on clinical outcomes, including mortality, hepatocellular carcinoma (HCC) incidence, and hepatic decompensation, in patients with MASLD.

Methods: This study investigates the impact of statin use on outcomes in patients with MASLD. A population-based study cohort was analyzed using data from the UK Biobank, which included 402,476 participants after exclusions. Inverse probability of treatment weighting (IPTW) was utilized to balance baseline characteristics. The primary outcomes included all-cause mortality and liver-related mortality, with secondary outcomes covering the incidence of HCC and hepatic decompensation. Subgroup analyses were conducted to assess the effects of specific statin types and gender differences.

Results: Statin use correlated with a 19% reduction in all-cause mortality and a 37% reduction in liver-related mortality in the MASLD cohort. Notably, atorvastatin was significantly effective in reducing all-cause mortality, liver-related mortality, hepatic decompensation, and HCC risk. Gender-specific analyses demonstrated that female statin users experienced the most significant reductions in mortality and HCC incidence. Statin use significantly improved survival and decreased liver-related outcomes in MASLD patients, with gender-specific analyses showing enhanced effects for female users.

Conclusions: The findings suggest the importance of statin selection and highlight that gender-specific strategies may enhance treatment efficacy in the MASLD cohort.

Background and objective: Primary sclerosing cholangitis (PSC) is an autoimmune biliary fibrosing disease characterized by inflammation and injury of the intra- and/or extrahepatic bile ducts. The pathogenesis of PSC is poorly understood but is believed to be multifactorial, involving genetic predisposition, immunological dysregulation, and environmental influences. These may include disturbances in the gut-liver axis such as immune dysfunction in the colon and liver, alterations in the fecal and biliary microbiome, conjugation of bile acids into toxic species, and compromised intestinal epithelial integrity due to colitis, resulting in translocation of bacterial byproducts to the liver. There is a critical need for diagnostic and prognostic biomarkers that would enhance management and outcomes for patients with PSC. Additionally, validation of such biomarkers could serve as measurable endpoints when conducting future clinical trials. This aim of this paper is to review the available literature on candidate diagnostic and prognostic biomarkers in the adult and pediatric PSC populations.

Methods: Original studies investigating biomarkers in serum, bile, and tissue published until November 2024 were systematically searched on PubMed, with a specific focus on newer studies published in the past 10 years and pediatric studies. Small studies with fewer than 10 patients in each study group, animal model studies, and studies with a focus on biomarkers for cholangiocarcinoma were excluded.

Key content and findings: Diagnostic and prognostic biomarkers summarized in this review include autoantibodies, markers of innate and adaptive immune responses, extracellular vesicles, epigenetic modifications, microbiome, proteins involved in lipid metabolism and bile acid homeostasis, and markers of fibrogenesis. Novel concepts for future biomarker discovery and implementation, including the potential for insights to be gained from the pediatric PSC population, are explored.

Conclusions: There is a critical need for further biomarker discovery for PSC as it will provide clues to disease pathogenesis and uncover candidate targets for therapeutic intervention.