Journal of Gastroenterology and Hepatology最新文献

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.

Background and aim: Colorectal cancer (CRC) is a significant global health burden, and screening can greatly reduce CRC incidence and mortality. Previous studies investigated the economic effects of CRC screening. We performed a systematic review to provide the cost-effectiveness of CRC screening strategies across countries with different income levels.

Methods: We searched relevant scientific databases (PubMed, Embase, Ovid, Web of Science, Scopus) from January 1, 2010, to December 31, 2023. We selected English-language studies related to model-based economic evaluations of CRC screening strategies. Information such as the characters of screening tests, model characteristics, and key cost-effectiveness findings were collected. The net monetary benefit approach was used to compare the outcomes of various strategies.

Results: A total of 56 studies were identified, including 46 from high-income countries (HICs), 6 from upper-middle-income countries (UMICs), and 4 from lower-middle-income countries (LMICs). Most annual fecal occult blood tests and fecal immunochemical tests were cost-saving, and colonoscopy every 10 years was cost-saving. Other strategies involving multitarget fecal FIT-DNA detection, computed tomography colonography, and flexible sigmoidoscopy were cost-effective compared with no screening. Newer strategies such as magnetic resonance colonography every 5 years, annual urine metabolomic tests, and fecal bacterial biomarkers were cost-effective compared with no screening.

Conclusion: In our updated review, we found that common CRC screening strategies and magnetic resonance colonography continued to be cost-effective compared with no screening. Areas for further development include accurately modeling the natural history of colorectal cancer and obtaining more evidence from UMICs and LMICs.

Background: Resmetirom, the first FDA-approved drug for nonalcoholic steatohepatitis (NASH) with fibrosis in obese patients, when combined with lifestyle modifications, improves NASH resolution and reduces fibrosis by at least one stage. Low thyroid hormone (T₃) levels are linked to a higher risk of developing metabolic dysfunction-associated steatotic liver disease (MASLD). Epidemiological studies have confirmed the positive correlation between hypothyroidism and MASLD. Unraveling the molecular mechanisms of T₃ signaling pathways in MASLD will enhance the prospects of identifying effective and specific targets. Therefore, this review discusses the significant role of thyroid hormones in the homeostasis of fat metabolism and describes the possible molecular mechanisms of thyromimetics in the treatment of MASLD.

Methods: A comprehensive search in PubMed and EMBASE was conducted using the keywords "thyromimetics and liver diseases," "thyroid hormone and liver diseases," "hypothyroidism and liver diseases," "T₃, T₄ and liver disease," and "resmetirom and liver disease." Relevant papers published before October 2024 were included.

Results: T₃ treatment enhances mitochondrial respiration, biogenesis, β-oxidation, and mitophagy, reducing liver lipid accumulation. However, T₃ treatment causes cardiotoxicity through thyroid hormone receptor (THR)α agonistic activity. To address this, molecules with high THRβ agonistic but lower THRα activity have been developed. Besides resmetirom, other THRβ agonists like TG68, CS27109, MB07811, and KB-141 show promising results in experimental studies. These molecules upregulate THRβ target genes, activate genes for fatty acid β-oxidation in mitochondria and fatty acid breakdown in peroxisomes, downregulate the genes involved in de novo lipogenesis, reduce inflammation by downregulating NF-κB/JNK/STAT3 signaling pathways, and accelerate fibrosis resolution by downregulating the expressions of fibrosis marker genes in NASH liver tissue.

Conclusion: Future clinical studies should thoroughly investigate THRβ agonists, including TG68, CS27109, MB07811, and KB-141.

Background: Pit pattern diagnosis using crystal violet staining for colorectal tumors is useful for qualitative and depth diagnosis. However, due to its reported carcinogenic potential, the use of crystal violet has been restricted. This study was aimed at investigating the efficacy of texture and color enhancement imaging (TXI) magnification in pit pattern diagnosis.

Methods: This study enrolled consecutive patients with consent obtained and with colonic tumors indicated for magnifying endoscopy in which all modalities' images (magnified observation with crystal violet staining (CV), magnified white light observation with indigo carmine (IC-WLI), and magnified TXI observation with indigo carmine (IC-TXI)) were evaluable between July 2020 and January 2023. The visibility of the pit pattern using a 5-point Likert scale and its diagnostic accuracy were compared (IC-TXI vs. IC-WLI, reference: CV, by three experts).

Results: A total of 145 colorectal tumors from 145 patients were included. Visibility scores for the pit pattern were significantly higher with IC-TXI compared to IC-WLI (all three experts, p < 0.0001). The pit pattern match rate (Type II/III/IV/V) of IC-TXI compared to CV was also superior to IC-WLI (72.9% vs. 59.7%; p = 0.02).

Conclusions: IC-TXI provided reasonably good and higher visibility and diagnostic accuracy than IC-WLI for pit pattern diagnosis of colorectal tumors compared to CV, suggesting it as an alternative to CV.

Background: Clonorchis sinensis infection is an important risk factor for intrahepatic cholangiocarcinoma (ICC). C. sinensis positive (C.s+) ICC patients had much shorter overall survival (OS) compared with C. sinensis negative (C.s-) group. This study aims to explore the impact and underlying mechanism of C. sinensis infection on ICC progression.

Methods: In this study, ICC patients underwent surgery from two medical centers enrolled. RNA sequencing was used to determine the downstream activated pathways and genes. Furthermore, we demonstrated the potential mechanism of C. sinensis infection in promoting ICC progression through in vitro co culture systems and two animal models.

Results: Through RNA sequencing, we found fatty acid metabolism and the expression of fatty acid synthase (FASN), a key enzyme catalyzing long-chain fatty acid synthesis, were significantly elevated in C.s+ ICCs. Then, we found excretory/secretory products (ESPs) secreted by C. sinensis could significantly upregulate the expression of transcription factor E2F1, thereby promoting FASN expression and fatty acid synthesis in tumor cells, which ultimately accelerating tumor progression. However, the promotive effect disappeared when FASN was knocked down. Meanwhile, ESPs could promote tumor growth, increasing FASN expression and free fatty acid level in both subcutaneous and orthotopic mouse models.

Conclusion: This study indicates that C. sinensis infection could upregulate the level of FASN and activate fatty acid synthesis pathway, thereby accelerating ICC progression. This provides a new insight for the clinical treatment of ICC with C. sinensis infection.

Background and aim: Acute-on-chronic liver failure (ACLF) is characterized by fast progression and high mortality, with systemic inflammation and immune paralysis as its key events. While natural killer (NK) cells are key innate immune cells, their unique function and subpopulation heterogeneity in ACLF have not been fully elucidated. This study aimed to investigate the characteristics of NK cell subsets in the peripheral blood of patients with ACLF and determine their roles in the inflammatory responses.

Methods: Circulating NK cells (14 751 cells) from patients with ACLF and healthy controls (HCs) were subjected to single-cell RNA sequencing (scRNA-seq). Clustering and annotation were used to identify the features of NK cell subsets and the characteristics of disease progression in ACLF.

Results: Four NK cell subsets were obtained, including adaptive NK cells, mature NK cells, inflamed NK cells, and CD56^bright NK cells. Compared with the HCs, the patients with ACLF had a significantly lower proportion of Mature NK cells and a higher proportion of Inflamed NK cells. Quasi-temporal analysis showed that Inflamed NK cells were highly enriched in the late quasi-temporal sequence, and genes related to pro-inflammatory were significantly up-regulated in Inflamed NK cells. In addition, scRNA-seq and flow cytometry confirmed that the expression level of cell migration inducing hyaluronidase 2 (CEMIP2) in NK cells progressively increased from the HC group to the ACLF survival group and then to the ACLF death group.

Conclusions: scRNA-seq reveals that Inflamed NK cell subsets are associated with ACLF progression and poor prognosis. CEMIP2 may be a molecular marker for ACLF progression.