Translational gastroenterology and hepatology最新文献

Background: Pediatric primary sclerosing cholangitis (PSC) is a rare, chronic liver disease often associated with unfavorable outcomes. However, reliable prognostic markers in children remain limited. This observational cohort study aimed to identify clinical and laboratory markers associated with a severe liver disease course and to characterize the clinical progression of pediatric PSC.

Methods: We conducted a retrospective analysis of children with PSC treated at our tertiary transplant center between January 2011 and June 2023. The study evaluated laboratory markers [gamma-glutamyl transferase (GGT), total bilirubin, the aspartate aminotransferase (AST)-to-platelet ratio index (APRI), and the Sclerosing Cholangitis Outcomes in Pediatrics (SCOPE) index] at diagnosis, as well as GGT normalization within 1 year. In addition, we assessed clinical factors including sex, age at diagnosis, PSC subtype, presence of inflammatory bowel disease (IBD), and features of autoimmune hepatitis (AIH), in relation to the occurrence of severe complications. Severe complications were defined as biliary or portal complications, cholangiocarcinoma, liver transplant listing, or liver-related death.

Results: Sixty patients with PSC (40.0% female) were followed for a median of 3.8 years [interquartile range (IQR), 1.5-8.7 years]. IBD was present in 81.7% of cases, and 43.3% had features of AIH. The median age at diagnosis was 12 years (IQR, 9-15 years). Severe complications occurred in 17% of patients, including biliary complications (6.7%), portal complications (8.3%), cholangiocarcinoma (1.7%), and liver transplant listing (6.7%). No liver-related deaths were recorded. Event-free survival was 88.3% at 5 years and 71.5% at 10 years. No statistically significant differences in outcomes were observed based on the SCOPE index calculated at time of diagnosis or GGT normalization within 1 year. Similarly, elevated total bilirubin, GGT, and APRI index at diagnosis were not associated with worse outcomes.

Conclusions: Neither the SCOPE index at diagnosis nor GGT normalization within 1 year predicted severe liver disease course. No clinical factors (sex, age at diagnosis, presence of IBD, features of AIH, or PSC subtype) or laboratory markers were found to reliably predict a severe disease course. Overall, the long-term prognosis in this pediatric cohort was generally favorable.

Background and objective: Liver transplantation (LT) is the most effective end-stage liver disease (ESLD) therapeutic intervention. However, in China, many liver transplant recipients lack a comprehensive management approach. This narrative review summarizes the current deficiencies in long-term post-transplant care and proposes a comprehensive model for Integrated Care Management (ICM) aimed at improving long-term outcomes after LT.

Methods: An extensive electronic literature search was performed using PubMed database to identify relevant articles. The search included prospective clinical trials, observational trials, case-control studies, systematic reviews with or without meta-analysis. Articles were limited to English and Chinese language publications. The following Medical Subject Headings (MeSH) terms and free-text keywords were combined with Boolean operators: ("liver transplantation" OR "liver transplant*" OR "orthotopic liver transplantation" OR "OLT") AND ("postoperative management" OR "whole-course management" OR "perioperative care" OR "long-term follow-up") AND ("immunosuppress*" OR "tacrolimus" OR "cyclosporine" OR "mycophenolate" OR "infection prophylaxis" OR "graft function" OR "rejection" OR "biliary stricture" OR "hepatic artery thrombosis" OR "renal dysfunction" OR "hepatitis B recurrence" OR "hepatitis C recurrence").

Key content and findings: Research has shown the global number of LT recipients continues to rise, affecting millions of individuals and placing a substantial burden on healthcare systems worldwide. Despite considerable progress over the past three decades in surgical techniques, perioperative care, and immunosuppressive therapy, long-term post-transplant management has received comparatively limited attention from both the public and policy-makers. This neglect has contributed to suboptimal long-term outcomes, including increased mortality and reduced quality of life among recipients.

Conclusions: A comprehensive model for ICM may be a new direction to improve the long-term outcomes after LT in the future.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a metabolic syndrome characterized by increased fat storage in hepatocytes. In the hepatocytes, autophagy protects against cytotoxic stress and harmful cellular conditions. In the hepatic stellate cells (HSCs), autophagy exerts pro-fibrotic properties and promotes the release of pro-inflammatory metabolites. We investigated the modulation of autophagy as a therapeutic approach for MASLD.

Methods: Murine liver tissue and human hepatic cells were analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot. Real time fluorescence was performed to monitor the autophagy maturation process. Accumulation of fat was detected by Oil Red O staining. Collagen fibers were detected by picrosirius staining under polarized light.

Results: The loss of leptin in obese mice affected by metabolic dysfunction-associated steatohepatitis (MASH) promoted the over-expression of Becn1, Map1lc3b, Sqstm1, Uvrag and Prkaa1_2 and the accumulation of their proteins. The oleic acid caused an accumulation of fat, followed by the reduction of the autophagy proteins and the increase of the P-AMPK-α in LEP^-/- HepG2 cells and the maturation of autophagosome vesicles in LEP^-/- Hep3B cells. Oleic acid increased the accumulation of fat in human HSCs and the COL1A1 transcript level, but not the collagen I fibers. BECN1 and MAP1LC3B were up-regulated. Instead, all the autophagy proteins were downregulated, but not P-AMPK-α. Instead, the treatment with caffeine prompted neither the transactivation nor the autophagy.

Conclusions: Leptin loss contributes to the autophagy process in obese mice. The administration of oleic acid in LEP^-/- cells prompted autophagy not only in hepatocyte-like cells but also in human HSCs.

Background and objective: Coeliac disease (CeD) is a common, underdiagnosed enteropathy with rising incidence and diagnostic delay. This literature review synthesises advances in small bowel capsule endoscopy (SBCE) and artificial intelligence (AI) for SBCE, and outlines implications for clinical practice.

Methods: A comprehensive literature search in PubMed, Scopus, Embase, and Cochrane Library was conducted, where relevant articles published in English over the past ten years [2015-2025] were selected and analysed by two independent reviewers.

Key content and findings: Current evidence supports tissue transglutaminase immunoglobulin A (tTG-IgA) as the first-line test and endomysial antibody IgA (EMA-IgA) as a test to rule in disease. An adult no-biopsy pathway at ≥10 times the upper limit of normal (ULN) yields near-perfect specificity but modest sensitivity; therefore, histology remains the reference standard. Optimised biopsy protocols with ≥4 samples from the second part of the duodenum plus 1-2 samples from the bulb, which are well-oriented, increase diagnostic yield. SBCE complements oesophagogastroduodenoscopy (OGD) to map disease extent, detect complications, and guide care when biopsy is contraindicated. A positive baseline study may be prognostic. AI has progressed from per-frame villous atrophy (VA) detection (internal accuracy: 94-96%) to patient-level and severity curve methods showing high agreement with experts, enabling reproducible burden mapping. Across prospective studies and meta-analyses in mixed SBCE indications, AI assistance increases sensitivity without losing specificity and reduces review time approximately 10-12-fold. Gains are greatest for non-experts and for triage applications. Key limitations include small, single-centre datasets, inconsistent labelling, image frame analysis rather than full videos, data leakage risks, and uncertain generalisability across devices and populations. Priorities include multicentre, patient-wise external validation; harmonised International Capsule Endoscopy Research (I-CARE) lesion definitions; prevalence-aware calibration; equity-aware evaluation; and vendor-agnostic deployment.

Conclusions: AI-augmented SBCE can improve efficiency, consistency, and monitoring of CeD; however, adoption should remain human-in-the-loop and be anchored to safety protocols, including patency testing when retention risk is relevant. Equity considerations include serology-negative presentations in some populations and the need for calibrated thresholds aligned with real-world prevalence and costs.

Background: Given the increasing use of targeted therapies in clinical practice, we aimed to determine the clinically actionable safety profiles of second-line tyrosine kinase inhibitors (TKIs) in advanced hepatocellular carcinoma (HCC) by analysing adverse drug reactions (ADRs) reported in the WHO-VigiAccess database.

Methods: Retrospective descriptive analysis of ADR reports for cabozantinib and regorafenib in advanced HCC after first-line failure. Data included patient demographics, geographic distribution, system organ classes (SOCs) and preferred terms (PTs) (MedDRA v24.0). Chi-squared tests were used to compare patient characteristics; head-to-head disproportionality analysis [reporting odds ratio (ROR)] was performed for gastrointestinal (GI) disorders.

Results: A total of 51,404 reports were analysed (cabozantinib: 33,846; regorafenib: 17,558). Cabozantinib exhibited a significantly higher proportion of GI disorders (87.2% vs. 60.3%; P<0.001) and higher GI-related ROR [1.31; 95% confidence interval (CI): 1.29-1.33] than regorafenib (0.73; 95% CI: 0.71-0.74). Diarrhoea was the most frequent ADR with cabozantinib (23.7%), whereas fatigue dominated regorafenib reports (16.3%). Death-related ADRs were similar (cabozantinib 6.36%; regorafenib 5.96%).

Conclusions: Cabozantinib carries a disproportionately higher risk of severe GI toxicity compared with regorafenib. Clinicians should consider prophylactic anti-diarrhoeal therapy, routine liver-function monitoring, and early dose modifications when initiating cabozantinib, especially in male patients aged 45-64 years. These data supported personalized second-line TKI selection after first-line failure.

Background: One of the objectives proposed by the World Health Organization (WHO) for the period 2022-2030 is to employ new strategies to combat hepatitis. Since universal screening has not been implemented in Spain, opportunistic screenings are being conducted in different healthcare settings. This work analyses the efficiency of this process on the south-eastern region of Spain (Alicante).

Methods: The efficiency of screening to detect hepatitis C virus (HCV) conducted in emergency, gynecology, surgery, primary care, nephrology, occupational risk accidents, and hematology (opportunist screenings) was compared against the screening conducted in prisons and in vulnerable populations (decentralized screening) using dry blood spot (DBS) testing between 2017 and 2023. The screening cost was calculated applying the Fee Law of the Valencian Community.

Results: A total of 66,532 samples were analyzed, out of which viral genome was detected in 315 (0.47%). The prevalence of HCV-positive antibodies in patients from healthcare settings was 0.44%, of which 0.14% had detectable viral RNA (vRNA). In contrast, decentralised screening detected 27.28% positive HCV antibodies and 10.28% viral genomes. In this context, prisons showed a prevalence of positive antibodies and vRNA of 7.39% and 3.30%, respectively. In DBS samples, the prevalence of positive antibodies was 19.89%, with 6.98% showing vRNA. When analyzing the costs of screening processes, the costs of screening patients from gynecology are 89,966 € per patient positive for vRNA, decreasing to 6,744 € in primary care, to 2,983 € in the emergency department, to 518 € in prisons and to 405 € in DBS.

Conclusions: Focusing on opportunistic screening, the most cost-effective approach is carried out in the emergency department. Regarding decentralized screening, this study has demonstrated that it is highly effective in our setting, as it targets disadvantaged populations with a high prevalence of infection. Therefore, this screening should be promoted and evaluated to establish its efficacy elsewhere and to advance the detection of patients infected with HCV.

Background and objective: Infant perianal abscess (PA) and fistula-in-ano (FIA) are a relatively rare clinical entity for which optimal management continues to be highly variable and debated by physicians. This review seeks to describe the current literature on the pathogenesis, clinical presentation, and management of PA and FIA.

Methods: The current literature was queried utilizing publicly available free databases including the National Institute of Health Library of Medicine MEDLINE, PubMed, Embase, and Cochrane Library for manuscripts published from 1948 to 2025 using MeSH search terms associated with PA and FIA in infants. Resultant articles were screened for relevance, summarized, and compiled into a narrative. Retrospective cohort studies were compared and bias assessed using the Newcastle-Owatta Score.

Key content and findings: Infant PA and FIA exhibit a male predominance. Proposed theories of pathogenesis relate to abnormal anal crypt development, hormonal influence, and infant-specific risk factors. Optimal clinical management continues to be debated with some studies advocating for initial conservative management while others suggesting early surgical management is superior. Ten comparative retrospective studies were appraised and found to have differing conclusions on superiority. Notably these studies differed in their studied population and their definitions of conservative management.

Conclusions: The current data is limited in its ability to definitively determine the superiority of conservative versus operative management and further hampered by the lack of a standard definition of conservative management. Consensus definitions and quality prospective trials are needed to fully understand this clinical entity. Nonetheless, the current literature suggests a trial of conservative management can be safe and effective.

Background and objective: Artificial intelligence (AI) has revolutionized the field of gastroenterology, leading to significant improvements in the diagnosis, management, and prognosis of several gastrointestinal (GI) disorders. With this context in mind, this brief review examines a wide range of subjects, including the history of AI in medicine and the state of AI in gastroenterology today, with a particular emphasis on its application in radiographic diagnosis, endoscopic procedures, disease detection, and clinical decision-making.

Methods: A narrative review of the literature was conducted, encompassing studies published in English across major databases. The review covers historical developments of AI in medicine, contemporary AI applications in gastroenterology, and emerging trends.

Key content and findings: AI techniques, including machine learning and deep learning, have demonstrated high accuracy in detecting GI pathologies such as polyps, neoplasms, inflammatory bowel disease, and other conditions. AI applications in endoscopy, video capsule endoscopy, and colonoscopy enable rapid analysis of large datasets, aiding early diagnosis and clinical decision-making. Challenges identified include data quality, model interpretability, ethical concerns, and liability associated with AI-assisted clinical decisions. Despite these challenges, AI continues to enhance gastroenterology practice and shows promise for broader clinical adoption.

Conclusions: AI has significant potential to improve patient care in gastroenterology. Future advancements will require collaboration among AI developers, clinicians, and patients to address implementation barriers, optimize clinical utility, and inform policy and research directions.