Journal of Gastroenterology and Hepatology最新文献

Background: Epithelial-mesenchymal transition (EMT) is central to HCC metastasis, in which RNA-binding proteins (RBPs) play a key role.

Methods: To explore the role of RBPs in metastasis of hepatocellular carcinoma (HCC), whole transcriptome sequencing was conducted to identify differential RBPs between HCC with metastasis and HCC without metastasis. The influence of RBPs on metastasis of HCC was verified by in vitro and in vivo experiments. The interaction of RBPs with non-coding RNAs was evaluated by RNA immunoprecipitation and pull-down assays. RNA sequencing, whole-genome sequencing, and alternative splicing analysis were further performed to clarify post-transcriptional regulation mechanisms.

Results: Whole transcriptome sequencing results showed that expression of thioredoxin (Trx) was significantly upregulated in HCC patients with metastasis. Trx was also found to be associated with poor prognosis in HCC patients. Overexpression of Trx could promote migration and invasion of HCC cells in vitro and increase the rate of lung metastasis of HCC cells in vivo. Moreover, binding assays showed that Trx could bind to LINC00152. As a result, LINC00152 was verified to determine the pro-metastasis function of Trx by knockdown assay. Furthermore, we revealed that Trx could regulate metastasis-associated alternative splicing program. Specifically, angiopoietin 1 (ANGPT1) was the splicing target; the splicing isoform switching of ANGPT1 could activate the PI3K-Akt pathway, upregulate EMT-associated proteins, and promote migration and invasion of HCC cells.

Conclusions: We found that Trx could interact with LINC00152 and promote HCC metastasis via regulating alternative splicing, indicating that Trx may serve as a novel therapeutic target for HCC treatment.

Background and aim: Accurate stratification of the risk of lymph node metastasis (LNM) following endoscopic resection of submucosal invasive (T1) colorectal cancer (CRC) is imperative for determining the necessity for additional surgery. In this systematic review, we evaluated the efficacy of prediction of LNM by artificial intelligence (AI) models utilizing whole slide image (WSI) in patients with T1 CRC.

Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review was conducted through searches in PubMed (MEDLINE), Embase, and the Cochrane Library for relevant studies published up to December 2023. The inclusion criteria were studies assessing the accuracy of hematoxylin and eosin-stained WSI-based AI models for predicting LNM in patients with T1 CRC.

Results: Four studies met the criteria for inclusion in this systematic review. The area under the receiver operating characteristic curve for these AI models ranged from 0.57 to 0.76. In the three studies in which AI performance was compared directly with current treatment guidelines, AI consistently exhibited a higher area under the receiver operating characteristic curve. At a fixed sensitivity of 100%, specificities ranged from 18.4% to 45.0%.

Conclusions: Artificial intelligence models based on WSI can potentially address the issue of diagnostic variability between pathologists and exceed the predictive accuracy of current guidelines. However, these findings require confirmation by larger studies that incorporate external validation.

Background and aim: Type 2 diabetes mellitus (T2DM) is intrinsically linked to various etiologies of liver disease, with 69% of patients having concomitant metabolic dysfunction-associated steatotic liver disease (MASLD). Studies suggest glucagon-like peptide-1 receptor agonists (GLP-1RAs) can ameliorating liver disease. With this analysis, we address the gap in knowledge about the effectiveness of these agents in preventing different major adverse liver outcomes (MALOs).

Methods: PubMed, Embase, and The Cochrane Central of Trials were searched for articles reporting MALOs in T2DM patients. Publication bias-identifying methods, quality assessment and sensitivity analyses (subgroup analyses, leave-one-out meta-analyses, and meta-regression) were employed. Statistical analyses were performed in R using the "meta" and "metafor" packages.

Results: Nine cohort studies from 535 identified articles encompassing 579 256 T2DM patients were included in the main analyses. GLP-1RA use was associated with reduced risks of hepatocellular carcinoma (HR 0.74, 95% CI 0.56-0.96) and cirrhosis decompensation (HR 0.68, 95% CI 0.65-0.72). Within the latter, variceal bleeding and hepatic encephalopathy prevention were found to be significantly reduced. Egger's test, Begg's test, and funnel-plot analysis yielded no publication bias. No significant differences were observed in preventing cirrhosis or hepatic failure. Meta-regression analysis revealed a positive correlation between hepatocellular carcinoma incidence and both male sex and longer follow-up duration.

Conclusions: This meta-analysis improves our understanding of the hepatoprotective effects of GLP-1RAs in T2DM patients and supports existing research, exhibiting superiority over other antidiabetic medications for hepatoprotection in this subgroup. Additional long-term follow-up studies are necessary to further validate these findings.

Although significant progress has been made in developing preclinical models for metabolic dysfunction-associated steatotic liver disease (MASLD), few have encapsulated the essential biological and clinical outcome elements reflective of the human condition. We conducted a comprehensive literature review of English-language original research articles published from 1990 to 2023, sourced from PubMed, Embase, and Web of Science, aiming to collate studies that provided a comparative analysis of physiological, metabolic, and hepatic histological characteristics between MASLD models and control groups. The establishment of a robust metabolic dysfunction-associated steatotic liver rodent model hinges on various factors, including animal species and strains, sex, induction agents and methodologies, and the duration of induction. Through this review, we aim to guide researchers in selecting suitable induction methods and animal species for constructing preclinical models aligned with their specific research objectives and laboratory conditions. Future studies should strive to develop simple, reliable, and reproducible models, considering the model's sensitivity to factors such as light-dark cycles, housing conditions, and environmental temperature. Additionally, the potential of diverse in vitro models, including 3D models and liver organ technology, warrants further exploration as valuable tools for unraveling the cellular mechanisms underlying fatty liver disease.

Background and aim: The Rome IV criteria, the standard for diagnosing functional constipation (FC), deem the Bristol Stool Scale (BSS) unsuitable for assessing stool consistency in young children. Hence, the Brussels Infant and Toddler Stool Scale (BITSS) was developed. We aimed to validate and test the reliability of BITSS for hard stools and FC among infants and toddlers, where there is limited evidence in Asian populations.

Methods: The research evaluated FC in children aged 0-48 months who came for medical examination using Rome IV criteria. Stool properties provided by caregivers were assessed sequentially through three methods: the BSS, the BITSS, and caregiver reports.

Results: A total of 370 responses were received, with an average age of 26.2 months. Substantial agreement was observed between the BITSS and caregiver reports for hard stools (concordance rate: 91.9%, κ = 0.75), while near-perfect agreement was found between BITSS and BSS (concordance rate: 93.5%, κ = 0.81). The BITSS exhibited higher sensitivity than the BSS in assessing hard stools (95.3% vs 87.5%, P < 0.001). And the BITSS (23.5%) identified the highest prevalence of FC than the BSS (20.5%) and caregiver report (18.7%), with near-perfect agreement. Moderate agreement was reported when evaluating the test-retest reliability between BITSS and caregiver reports (concordance rate: 86.2%, κ = 0.44).

Conclusions: The BITSS, more sensitive than the BSS in identifying abnormal, especially hard stools, aids in early FC detection in young children. These findings support using BITSS over BSS for evaluating hard stools in infants and toddlers, both in Vietnam and globally.

Alcohol-associated liver disease (ALD), including alcoholic fatty liver, is a serious problem in many countries, and its economic costs to society are enormous. There is evidence indicating the relations between gut environments and liver disease, and thus, improvement of gut environment is expected to be an effective approach for ALD prevention. In this study, we explored the preventive effect of partially hydrolyzed guar gum (PHGG) on ALD focusing on the gut-liver axis. Two weeks of PHGG pre-feeding suppressed the liver fat accumulation in the experimental binge alcohol model mouse. In cecal microbiome, PHGG pre-feeding increased beneficial Bifidobacterium with its metabolite acetate concentration and suppressed the alcohol-induced increase in the potential pathobiont Streptococcus. PHGG pre-feeding increased colonic gene expression of angiogenin genes, which act as antimicrobial peptides and decreased expression of genes for mast cell protease, which suggests a potential involvement in leaky gut. Correlation network analysis based on evaluated parameters revealed four relations worth noticing. (i) The abundance of Bifidobacterium positively correlated with cecal acetate. (ii) Cecal acetate negatively correlated with Streptococcus via colonic angiogenin expression. (iii) Streptococcus positively correlated with liver fat area. (iv) Cecal acetate had direct negative correlation with liver fat area. Considering these relations comprehensively, acetate produced by Bifidobacterium may be a key mediator in ALD prevention; it inhibited growth of potential pathobiont Streptococcus and also directly regulated liver lipid metabolism reaching through portal vein. This study demonstrated that regularly intake of PHGG may be effective in reducing the risk of alcoholic fatty liver via gut-liver axis.

Background and aim: Worldwide, the incidence of colorectal cancer (CRC) continues to rise and remains a major public health concern. This study aimed to analyze the temporal and spatial trends in CRC incidence and related risk factors at the country level.

Methods: Data on CRC and related risk factors were obtained from the Global Burden of Disease Study (GBD) 2019 study. Temporal trends were evaluated using estimated annual percentage change while spatial trends were analyzed using spatial autocorrelation and autoregression. Additionally, linear mixed-effects models were employed to identify risk factors linked to CRC incidence.

Results: Globally, from 1990 to 2019, the incidence cases of CRC increased by 157.23%. At the national level, the incidence of CRC increased in most countries, with the highest increases of age-standardized incidence rate (ASIR) in Equatorial Guinea, Vietnam, and China. In both 1990 and 2019, global spatial clustering of CRC ASIR highlighted hotspots in Europe, characterized by elevated CRC ASIR levels. A comparative analysis of risk factors between hotspot countries and others indicated that gender and alcohol use exerted greater influence in hotspots than elsewhere.

Conclusion: Although from 1990 to 2019, the highest growth in ASIR of CRC has been observed in African, Asian, and Latin American countries, the hotspots are still concentrated in Europe. In the identified hotspots, gender and alcohol use exert a more significant impact on CRC incidence compared with other countries. Thus, we should pay attention to countries where the CRC incidence is increasing and these risk factors.

Background and aim: The characteristics of autoimmune liver diseases (AILDs), including primary biliary cholangitis (PBC), autoimmune hepatitis (AIH), and PBC-AIH overlap syndrome (OS), have rarely been investigated and compared in Asia.

Methods: At the Taiwan tertiary referral center, 330 PBC patients (87% treated with ursodeoxycholic acid [UDCA]), 143 AIH patients (94.4% treated with immunosuppressive therapy [IST]) and 21 PBC-AIH OS patients (85.7% treated with UDCA and IST) were enrolled.

Results: Compared with AIH patients, PBC patients were older at baseline and had greater female-to-male sex ratios, alkaline phosphatase (ALP) and γ-glutamyl transferase (γ-GT) levels, and liver cirrhosis (LC), dyslipidemia, and hepatic and cardiometabolic complication rates. PBC patients had the lowest transaminase levels, whereas AIH patients had the highest transaminase levels. PBC patients had greater 22-year all-cause mortality and liver transplantation (ACMaLT) (43.5 vs 25.4%, P = 0.004), LC (75 vs 58.5%, P < 0.01), dyslipidemia (54.4 vs 45.9%, P = 0.001), and cerebrovascular accident (11.3 vs 0.8%, P = 0.019) cumulative incidences (CIs) than did AIH patients; PBC-AIH OS patients had greater systemic lupus erythematosus (28.9 vs 8.9%, P = 0.009) CI than did PBC patients. Baseline ALP (hazard ratio: 1.001), albumin (0.514), platelet count (0.997), and LC (3.438) were associated with ACMaLT; age (1.110), albumin (0.350), cirrhosis (46.219), and hepatitis C virus antibody positivity (5.068) were associated with hepatocellular carcinoma (HCC); and female sex (2.183) and body mass index (1.054) were associated with autoimmune diseases.

Conclusions: Compared with AIH patients, PBC patients had greater cardiometabolic CI, and ACMaLT CI, which was associated with cholestasis, liver functional reserve and LC. Older AILD patients with LC and females with obesity demand special caution for the development of HCC and extrahepatic autoimmune diseases, respectively.

Background and aim: Endoscopic resection (ER) is widely performed to treat early colorectal cancer. However, additional surgery for pathological T1 colorectal cancer (pT1CRC) after ER is controversial because of the imprecise prediction of lymph node metastasis (LNM). Recently, several patients of pT1CRC with lymphoid follicular replacement (LFR) without LNM have been reported. This study aimed to investigate the clinicopathological features and risk of LNM in patients with pT1CRC with LFR.

Methods: We retrospectively analyzed patients who underwent ER or surgical resection and were diagnosed with pT1CRC between January 2010 and December 2020. We defined pT1CRC with LFR as the replacement of a part of the lymphoid follicular component within the submucosal area by adenocarcinoma, with no invasion into other submucosal areas.

Results: Among the 600 eligible patients, the incidence rate of pT1CRC with LFR was 6.7% (40/600). Patients with pT1CRC with LFR represented 14.3% (37/258) of the endoscopically treated patients and 0.9% (3/342) of the surgically treated patients. For patients with pT1CRC with LFR, 80.0% (32/40) had flat and depressed lesions, and 35.0% (14/40) had submucosal invasion depth ≥1000 μm. Patients with pT1CRC with LFR had negative lymphovascular invasion, differentiated type, and budding grade 1. In the median follow-up of 61 months, patients with pT1CRC with LFR had no LNM.

Conclusions: The presence of LFR in pT1CRC may be associated with a low risk of LNM. In patients with pT1CRC with LFR, follow-up without additional surgery is possible even if the submucosal invasion depth is ≥1000 μm.