Journal of Gastroenterology and Hepatology最新文献

Background and aim: Although nonalcoholic fatty liver disease (NAFLD) and lipoprotein(a) [Lp(a)] are associated with cardiovascular diseases, existing data on Lp(a) in NAFLD are conflicting. The aim of this systematic review and meta-analysis was to summarize and compare data on circulating Lp(a) between NAFLD patients and non-NAFLD controls.

Methods: A systematic literature search was performed in PubMed, Scopus, and Cochrane Library. This meta-analysis included 18 studies containing data on 74 691 individuals (20 220 patients with NAFLD and 54 471 controls).

Results: Circulating Lp(a) was similar between patients with NAFLD and controls (standardized mean difference [SMD] 0.09; 95% confidence interval [95% CI] -0.21, 0.38). The heterogeneity among studies was high (I² = 100%); no publication bias was detected (Egger's test P = 0.941). However, in subgroup analysis, Lp(a) was lower in NAFLD patients than controls, when Lp(a) was measured with nephelometry (SMD -0.26; 95% CI -0.46, -0.06), but not turbidimetry; this analysis also resulted in mild reduction of heterogeneity within the subgroup of nephelometry (I² = 87%). The sensitivity analyses, based on the exclusion of studies with Newcastle-Ottawa Scale score ≤6 (n = 5), studies in which liver biopsy was used for NAFLD diagnosis (n = 4) or studies that adopted the criteria of metabolic dysfunction-associated fatty liver disease (n = 2), and meta-regression analysis did not explain the high heterogeneity among studies.

Conclusions: Overall, circulating Lp(a) was similar between NAFLD patients and non-NAFLD controls; however, patients with NAFLD had lower circulating Lp(a) compared with controls, when Lp(a) was measured with nephelometry. These results should be cautiously interpreted, because of the high heterogeneity among studies.

Background and aim: The rising prevalence of IBD globally has raised concerns about antibiotic exposure. This study's meta-analysis examines antibiotic exposure, frequency, year before diagnosis, regional differences, and IBD incidence.

Methods: The literature review used PubMed, Web of Science, Elsevier, ScienceDirect, and Cochrane CENTRAL databases up to June 2024 to explore the link between antibiotic exposure and IBD risk. Stratified analysis was conducted by years of antibiotic exposure before IBD diagnosis, frequency, and region. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were combined using a random effects model.

Results: Eighteen case-control studies and five cohort studies were included (n = 99, 104 IBD patients and n = 2 273 336 controls). The findings indicate that antibiotic exposure significantly has a positive association with the risk of developing IBD (OR, 1.66; 95% CI, 1.28-2.16). Antibiotic exposure of ≥3 years (OR, 1.49; 95% CI, 1.12-1.98), 2 years (OR, 1.46; 95% CI, 1.37-1.55), and ≤1 year (OR, 1.55; 95% CI, 1.17-2.04) prior to the diagnosis of IBD is associated with a higher risk of developing IBD. Cumulative exposure of ≥3 dispensations (OR, 2.02; 95% CI, 1.49-2.74) and two dispensations (OR, 1.36; 95% CI, 1.03-1.78) also had a positive association with IBD risk, while one dispensation did not (OR, 0.96; 95% CI, 0.72-1.26). No significant association was found in developing countries (OR, 1.92; 95% CI, 0.71-5.19), but developed countries showed a significant positive association with the risk (OR, 1.58; 95% CI, 1.27-1.96).

Conclusion: The meta-analysis suggests that antibiotic use has a positive association with the risk of IBD, and limiting unnecessary antibiotic use may be one way to reduce the risk of developing IBD.

Background and aim: Oral and esophageal cancers are globally prevalent, especially in East Asia. Over half of head and neck cancer patients developing second primary esophageal cancer (SPEC) were initially diagnosed with oral cavity cancer (OCC). This study assessed the cost-effectiveness of universal endoscopic screening for early SPEC prevention in newly diagnosed OCC patients at different stages.

Methods: This study employed Markov cohort models to evaluate the cost-effectiveness of endoscopic SPEC screening post-OCC diagnosis (stages 0 to IV) between screened and non-screened groups. Four surveillance frequencies were assessed: (i) one time, (ii) annual for 3 years, (iii) annual for 10 years, and (iv) annual for life. A hypothetical cohort of 100 000 cases across stages was compared for costs and quality-adjusted life-years (QALYs), discounted annually at 3%.

Results: All four screening strategies were beneficial for all OCC stages, especially for early-stage patients, resulting in higher QALYs. Lifetime/annual screening from the payer's perspective proved most favorable, with incremental QALYs of 1.23 at stage 0 and 0.06 at stage IV. Incremental costs for this strategy ranged from NTD 121 331 (USD 4044) at stage 0 to NTD 13 032 (USD 434) at stage IV. Both incremental costs and incremental cost-effectiveness ratio (ICER) values indicated cost savings from a societal perspective. The ICER values ranged from NTD -626 440 (USD -20 881) at stage 0 and NTD -475 021 (USD -15 834) at stage IV.

Conclusions: Overall, our study provided cost-effectiveness evidences to understanding the cost-effectiveness of endoscopic screening in OCC patients, particularly emphasizing the benefits of early and consistent screening.

Background and aim: Kui-Jie-Ling capsule (Kui-Jie-Ling) is a hospital preparation for ulcerative colitis (UC) in China. This study aimed at evaluating the protective effects and mechanisms of Kui-Jie-Ling and Kui-Jie-Ling combined with adalimumab on UC induced by dextran sulfate sodium (DSS).

Methods: Network pharmacology was combined with an animal experiment to reveal the targets of Kui-Jie-Ling alleviating UC. The UC model was established by drinking 2.5% DSS solution for 7 days. On the second day, the mice in the Kui-Jie-Ling group were orally administered with Kui-Jie-Ling (1.5 and 3.0 g/kg) daily for seven consecutive days, and the mice in the combination group were orally administered with Kui-Jie-Ling (3.0 g/kg) once a day for seven consecutive days and received one subcutaneous injection of adalimumab. The disease activity index, the colon length, the spleen index, the cytokines, the colon, the short-chain fatty acid content, and the gut microbiota in the colon were analyzed. The role of gut microbiota against UC was verified by fecal microbiota transplantation experiments.

Results: The animal study's results were consistent with the network pharmacology analysis, which reflected that Kui-Jie-Ling alleviated UC via multi-pathway. Kui-Jie-Ling ameliorated UC by inhibiting the formation of neutrophil extracellular traps (NETs), regulating inflammatory factors through the lipopolysaccharide-toll-like receptor 4/nuclear factor kappa B and interleukin-23-Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway, and restoring intestinal homeostasis.

Conclusion: These studies provided the experimental basis for the clinical administration of Kui-Jie-Ling and Kui-Jie-Ling combined with adalimumab against UC.

The m6A reader insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1) is involved in multiple pathophysiological processes through enhanced expression of the proteins encoded by their target mRNAs. However, the functional role of IGF2BP1-mediated m6A in liver fibrosis remains elusive. Here, we report that IGF2BP1 is highly expressed in activated hepatic stellate cells (HSCs), the major driver of fibrogenesis, and TUBB4B is identified as a potential target of IGF2BP1 by re-analysis of the RNA-seq, RIP-seq, and m6A-seq data. The relevant findings were subsequently demonstrated by a series of molecular and cellular evidences. The knockdown of IGF2BP1 or TUBB4B and pharmacological inhibition of TUBB4B by mebendazole treatments significantly suppress the proliferation, migration, and activation of HSCs. Mechanistically, IGF2BP1 upregulates TUBB4B expression through stabilizing TUBB4B in an m6A-dependent manner, and TUBB4B induces liver fibrosis by activating the FAK signaling pathway. Collectively, our results indicate that targeting IGF2BP1/TUBB4B/FAK axis in HSCs could be a promising therapeutic approach for liver fibrosis.

Background and aim: As the population ages, the number of elderly patients with superficial esophageal squamous cell carcinoma (ESCC) is increasing. We aimed to clarify the indications for endoscopic resection (ER) in late-elderly patients with ESCC in terms of life expectancy.

Methods: Patients aged ≥75 years who underwent ER for ESCC at our institution from January 2005 to December 2018 were enrolled. Clinical data, including the Eastern Cooperative Oncology Group performance status, American Society of Anesthesiologists physical status (ASA-PS), Charlson comorbidity index, and prognostic nutritional index (PNI), were collected at the time of ER. The main outcome measure was overall survival (OS).

Results: Two hundred eight consecutive patients were enrolled. The patients' median age was 78 years (range, 75-89 years). The 5-year follow-up rate was 88.5% (median follow-up period, 6.6 years). The 5-year OS rate was 79.2% (95% confidence interval [CI], 72.2-84.8), and 5-year net survival standardized for age, sex, and calendar year was 1.04 (95% CI, 0.98-1.09). In the multivariate analysis, an ASA-PS of 3 (hazard ratio, 2.45; 95% CI, 1.16-5.17) and PNI of <44.0 (hazard ratio, 2.73; 95% CI, 1.38-5.40) were independent prognostic factors. When neither of these factors was met, the 5-year OS rate was 87.8% (95% CI, 80.0-92.9), and 5-year net survival was 1.08 (95% CI, 1.02-1.14).

Conclusions: ER for ESCC in late-elderly patients may improve life expectancy. ER is recommended in patients with a good ASA-PS and PNI.

Insulin resistance (IR) is a pathogenic factor in numerous metabolic diseases. The gut microbiota plays a crucial role in maintaining the function of the intestinal barrier and overall human health, thereby influencing IR. Dysbiosis of the gut microbiota can contribute to the development of IR. Therefore, it is essential to maintain a balanced and diverse gut microbiota for optimal health. Akkermansia muciniphila, a widely present microorganism in the human intestine, has been shown to regulate gastrointestinal mucosal barrier integrity, reduce endotoxin penetration, decrease systemic inflammation levels, and improve insulin sensitivity. Reduced abundance of A. muciniphila is associated with an increased risk of IR and other metabolic diseases, highlighting its correlation with IR. Understanding the role and regulatory mechanism of A. muciniphila is crucial for comprehending IR pathogenesis and developing novel strategies for preventing and treating related metabolic disorders. Individual variations may exist in both the gut microbiota composition and its impact on IR among different individuals. Further investigation into individual differences between A. muciniphila and IR will facilitate advancements in personalized medicine by promoting tailored interventions based on the gut microbiota composition, which is a potential future direction that would optimize insulin sensitivity while preventing metabolic disease occurrence. In this review, we describe the physiological characteristics of A. muciniphila, emphasize its roles in underlying mechanisms contributing to IR pathology, and summarize how alterations in its abundance affect IR development, thereby providing valuable insights for further research on A. muciniphila, as well as new drug development targeting diabetes.

Background and aim: Following the approval of the first agent for the management of metabolic dysfunction-associated steatohepatitis (MASH), identification of patients with fibrotic MASH (MASH with NAS ≥ 4 and fibrosis stage ≥ 2) is crucial. We assessed the performance of FibroScan-aspartate aminotransferase (AST) score (FAST) for ruling in/out fibrotic MASH.

Methods: We searched Medline, Cochrane Library, Web of Science, Scopus, and gray literature sources up to January 11, 2024. Studies were eligible if they assessed the accuracy of FAST score for the detection of fibrotic MASH using biopsy as the reference standard at previously reported thresholds (FAST ≥ 0.67 for ruling-in and ≤ 0.35 for ruling-out fibrotic MASH). We calculated pooled sensitivity and specificity estimates for FAST thresholds alongside 95% confidence intervals following bivariate random- effects models. We assessed the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework.

Results: We included 16 studies with 8838 participants. A FAST score ≥ 0.67 yielded a pooled specificity of 0.87 (0.82-0.90) while a FAST score ≤ 0.35 yielded a summary sensitivity of 0.88 (0.83-0.91). At a prevalence of 30%, the positive predictive value for ruling-in fibrotic MASH was 60% while the negative predictive value for ruling-out the target condition was 91%. AST levels, cirrhosis prevalence, and number of pathologists reviewing biopsies were sources of heterogeneity among studies. The certainty of evidence was low to very low.

Conclusions: FAST score can be used as a triage test for ruling out fibrotic MASH. Nevertheless, its low positive predictive value necessitates sequential testing for ruling-in fibrotic MASH.