Translational gastroenterology and hepatology最新文献

Background: One of the ultimate goals in liver transplantation (LT) can be to achieve an immunosuppression (IS)-free state. However, there remains a lack of reliable tools for non-invasively and precisely predicting spontaneous operational tolerance (OT) after LT. This study aimed to develop a powerful model based on a peripheral blood transcriptional biomarker panel for noninvasive prediction of OT in LT.

Methods: Based on the GSE28842 and GSE11881 datasets, the peripheral blood transcriptional biomarkers related to OT after LT before IS withdrawal were retrospectively identified by utilizing differential expression analysis and overlapping analysis. Multivariate logistic regression with the least absolute shrinkage and selection operator (LASSO) was used for model construction. Receiver operating characteristic curves, calibration plots, concordance index, and decision curve analysis were performed for comprehensive model evaluation.

Results: Three key genes (including IL2RB, SH2D1B, and KLRC1) related to OT in LT were identified. A three-gene score was constructed and displayed a good predictive efficacy for OT before IS withdrawal [area under the curve (AUC) =0.794, P<0.05]. Besides, a nomogram combining the three-gene score with the clinical feature (namely "pre-withdrawal time") was established and showed high clinical applicability and predictive accuracy (AUC =0.850, P<0.05), which was superior to that of "pre-withdrawal time" (AUC =0.745, P<0.05).

Conclusions: This model might make it feasible to non-invasively identify the propensity to achieve spontaneous OT among liver recipients undergoing IS therapy and safely achieve IS withdrawal.

Background: Steatotic liver disease (SLD) is prevalent among women with breast cancer, but the influence of hormonotherapy on its severity and progression remains uncertain. This study evaluated the prevalence, severity, and predictors of SLD in relation to hormone therapy.

Methods: In this cross-sectional study, women with breast cancer were stratified by endocrine therapy exposure and evaluated with liver transient elastography and ultrasound. A subset of patients exposed to hormone therapy was prospectively followed for approximately 24 months to assess changes in liver stiffness over time.

Results: Among 171 women [mean age 58±10 years; median follow-up 53 months (range, 1-315 months)], comorbidities included diabetes (26.9%), hypertension (53.2%), dyslipidemia (31.0%), and obesity (70.2%). Patients were divided into four groups: no hormone therapy (n=55, 32.2%), tamoxifen only (n=72, 42.1%), anastrozole only (n=16, 9.4%), and both drugs (n=28, 16.4%). SLD was present in 57.9% of participants, with no significant differences in steatosis prevalence (P=0.09) or liver stiffness (P=0.20) across groups. Liver stiffness ≥8 kPa occurred in 12.3%, and stiffness ≥12 kPa in 5.8%. Diabetes was independently associated with steatosis, and metabolic syndrome with advanced fibrosis, regardless of hormone therapy duration. Among 35 patients in the prospective sub-cohort, no significant changes in liver stiffness were detected after 24 months of continuous endocrine therapy.

Conclusions: Over half of the participants had SLD, with advanced fibrosis in ~10%. Metabolic factors were independently associated with SLD development and progression, regardless of hormone therapy exposure. Patients in continuous use of endocrine therapy had no dynamic changes in liver stiffness after 24 months of follow-up.

Background and objective: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide and remains a public health challenge despite widespread screening. Colonoscopy is the gold standard for screening by enabling detection and removal of precancerous lesions, yet it is not without its limitations. Interval CRCs still occur, largely due to variability in adenoma detection rate (ADR), the primary quality indicator of colonoscopy. Artificial intelligence (AI)-powered computer-assisted polyp detection (CADe) systems have emerged as promising tools to enhance colonoscopy performance. This review synthesizes current evidence on CADe in colonoscopy, highlighting clinical efficacy, limitations, and future directions.

Methods: This review is based on a comprehensive PubMed search of articles published from database inception through July 31, 2025, related to CADe and AI in colonoscopy. Eligible studies included randomized controlled trials (RCTs), systematic and narrative reviews, meta-analyses, observational studies, case reports, guidelines, consensus conferences, and comparative studies.

Key content and findings: Multiple RCTs and meta-analyses consistently demonstrate that the use of CADe in colonoscopy can increase ADR with minimal impact on colonoscope withdrawal time (WT). Benefits extend to both experienced and less experienced endoscopists across varied settings. However, concerns about false positive (FP) rates, automation bias, operator deskilling, system integration, generalizability, and long-term outcomes persist. Health-economic models suggest CADe may be cost-effective, though real-world cost-effectiveness and long-term outcome data remain limited. Emerging directions include integration with computer-assisted diagnosis tools (CADx), real-time histology prediction, and personalized surveillance strategies.

Conclusions: CADe can improve ADR and is a promising step toward consistent, high-quality, equitable CRC prevention. However, uncertainties remain regarding generalizability, cost-effectiveness, and long-term outcomes. Continued work with validation, post-market surveillance, and integration with CADx are critical to fully realize the potential of CADe.

Background: Breakthroughs in immunotherapy, targeted therapy, and locoregional therapy are transforming the treatment of hepatocellular carcinoma (HCC). Studies are investigating whether therapies can be used to downstage tumors to resection or escalate therapies to improve prognostic outcomes. However, there are no standard criteria for "high-risk resectable" HCC. This study aims to validate and compare the prognostic performance of three distinct models for defining "high-risk resectable" HCC in predicting recurrence and survival following upfront resection.

Methods: We used a prospectively collected database of 1,779 HCC patients from a single institution to validate 3 models for defining "high-risk resectable" HCC. Clinical parameters included tumor number, size, vascular invasion, alpha-fetoprotein (AFP), and technical resectability. Patients who underwent upfront liver resection were classified as "high-risk" or readily resectable according to each model. Logistic regression was performed to predict recurrence, 1-, and 3-year survival adjusting for age, sex, ethnicity, hepatitis B, C, metabolic-associated steatohepatitis (MASH), body mass index (BMI), history of diabetes, hyperlipidemia, hypertension, and each model as predictors. C-statistics were used for comparison.

Results: Of the 290 patients who underwent upfront liver resection, 109 experienced recurrences. Patients were classified as high-risk resectable by Technical Risk, Integrated Risk, and Simplified Integrated Risk models (60, 148, and 40 patients, respectively). The Integrated Risk model demonstrated the highest sensitivity for predicting recurrence and survival (63.3%, 79.6%, and 70.1% for recurrence, 1-, and 3-year survival, respectively). Although all models showed significant predictive value based on area under the receiver operating curve (AUROC), the Technical Risk and Simplified Integrated Risk models exhibited lower sensitivity but higher specificity.

Conclusions: The three models demonstrated strong predictive performance across a diverse cohort. The Integrated Risk model, incorporating both technical and prognostic parameters was the most sensitive for identifying patients at high risk who may benefit from escalated therapy. Future studies should incorporate these models into treatment escalation strategies for HCC.

Background and objective: Human serum albumin (HSA), a multifunctional plasma protein derived from the liver, plays a crucial role in the pathophysiology and management of liver diseases. Increasing research reveals that the non-colloid functions of HSA, especially its binding and transport of both endogenous and exogenous substances, are clinically important, beyond its well-characterized colloid effects such as maintaining oncotic pressure. In chronic liver diseases such as cirrhosis, impaired function of HSA disrupts its ligand-binding and detoxification processes, thereby leading to various complications. Common hepatic complications include metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH), hyperbilirubinemia, and iron overload. This narrative review aims to explore the clinical applications of the binding and transport functions of HSA in the diagnosis and treatment of liver diseases, with the objective of offering insights into the comprehensive management of these conditions.

Methods: A computerized search was performed in PubMed and Embase, restricting the results to articles published in English and Chinese from January 2000 to March 2025. The search keywords use Medical Subject Headings and related entry terms, including terms related to "serum albumin, human", "recombinant human albumin", "antineoplastic agents", "analgesics", "anti-bacterial agents", "diuretics", "antiviral agents", "fatty acids", "ferritins", "bilirubin", "protein conformation", and "Amino Acid Sequence". Additionally, inverse searches were conducted based on the identified papers in these databases to uncover further relevant studies that were not captured by the automated search process.

Key content and findings: HSA-ligand binding exerts substantial effects on drug pharmacokinetic profiles from a clinical perspective, thereby impacting therapeutic efficacy of antiviral and antimicrobial agents, along with management strategies for hepatocellular carcinoma (HCC). Additionally, the concept of effective albumin concentration (eAlb) is proposed and highlights albumin's physiological function beyond its absolute serum levels with marked eAlb depletion in cirrhosis restored by albumin treatment. The adoption of recombinant HSA (rHSA) as a substitute for HSA remains constrained, pending further validation of its ligand-binding properties compared with HSA.

Conclusions: This review elucidates structural, mechanistic, and clinical perspectives of HSA, and characterizes HSA as a prognostic biomarker as well as a therapeutic target, while emphasizing the critical need for standardized guidelines for optimal albumin use in liver disease.

Background: Inflammatory bowel disease (IBD), which encompasses Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic inflammation of the gastrointestinal tract. Anemia is a common complication in patients with IBD, significantly impacting quality of life. Hepcidin, the primary regulator of iron metabolism, exhibits increased expression during inflammatory states, contributing to the development of anemia of inflammation. Understanding the relationship between hepcidin and IBD is essential to improving the diagnosis and management of this complication. This article aimed to systematically review and synthesize the evidence on the associative and predictive utility of hepcidin as a biomarker for inflammatory activity, iron status, and anemia management in patients with IBD.

Methods: A systematic review (SR) (PROSPERO identification number: CRD42024375586) was conducted across the databases PubMed, PubMed PMC, BVS/BIREME, Scopus, Web of Science, Embase, EBSCOhost, and ProQuest, including studies published up to July 2024. The research question was structured using the PICO strategy (Patient/Problem, Intervention, Comparison, and Outcome) to guide study selection and analysis. Original articles investigating hepcidin expression in patients with IBD and its association with inflammatory markers and iron status were included. Study selection, data extraction, and methodological quality assessment were performed independently by three reviewers using the Rayyan platform.

Results: Of the 342 studies identified, 47 met the inclusion criteria for qualitative analysis. The majority of studies reported elevated hepcidin levels in patients with active IBD compared to healthy controls or patients in remission. Hepcidin expression was positively correlated with inflammatory markers such as C-reactive protein (CRP) and interleukin-6 (IL-6), and negatively correlated with serum iron parameters and hemoglobin levels.

Conclusions: Hepcidin plays a central role in the pathophysiology of anemia associated with IBD, reflecting systemic inflammatory status. Its quantification may represent a valuable tool for the differential diagnosis of anemia and for guiding targeted therapies. Further longitudinal studies are required to validate its routine clinical use.

Background: The monocyte-to-lymphocyte ratio (MLR), an emerging inflammatory immune indicator, has an unclear association with metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to evaluate the relationship between MLR and MASLD in the U.S. population and further explore its association with hepatic steatosis and liver fibrosis.

Methods: This cross-sectional study analyzed data from 6,801 participants in the 2017-2020 National Health and Nutrition Examination Survey (NHANES). Multivariable logistic regression and multivariable linear regression were used to assess the associations of MLR levels with MASLD, hepatic steatosis [controlled attenuation parameter (CAP)], and liver fibrosis. Smooth curve fitting, restricted cubic spline (RCS) analysis, and threshold effect analysis were used to explore the relationship between MLR and MASLD. Subgroup analyses and interaction tests were conducted by sex, body mass index (BMI), race/ethnicity, and smoking status.

Results: A total of 6,801 participants (mean age 48.61 years) were included in the analysis. After full adjustment for confounders, Ln(MLR) was significantly positively associated with MASLD risk [odds ratio (OR) =2.58, 95% confidence interval (CI): 1.99-3.35, P<0.001]. Ln(MLR) was also significantly positively associated with CAP, showing a clear dose-response trend; the RCS curve suggested a stronger association at higher Ln(MLR) levels. In contrast, linear and nonlinear analyses revealed no significant relationship between Ln(MLR) and liver stiffness measurement (LSM). Subgroup analyses showed that the association remained consistent across sex, race/ethnicity, BMI categories, and smoking status, with the strongest effect observed in non-Hispanic Black participants.

Conclusions: This study demonstrates that MLR is significantly associated with MASLD and hepatic steatosis risk, suggesting its potential utility in reflecting early steatosis and inflammatory status of the disease. The findings support the value of MLR as a potential inflammatory biomarker for MASLD. However, longitudinal studies are needed to further validate its predictive capability.

Background: Interleukin (IL)-17 is a key cytokine in various inflammatory disease. Targeting IL-17 signals blockage did not improve inflammatory bowel disease (IBD) clinically, but also even developed de novo enteritis in non-IBD subjects. Little is known about the effects of blocking IL-17 signaling on intestinal homeostasis. This study investigated intestinal immunity under the inhibition of IL-17 signaling.

Case description: Refractory patients with psoriasis who started receiving anti-IL-17 or anti-IL-17 receptor inhibitors were included in this case series. These patients never experienced IBDs. Evaluation for fecal immunochemistry test (FIT), fecal calprotectin (fCal), endoscopic findings, colonic mucosa histology, and fecal microbial composition before and 3 months after starting treatment on the subjects was performed. Fecal microbial composition was analyzed with 16S rRNA. We present a series of 5 cases. The median age was 64 years, the disease duration was 31 years, two were female, four received secukinumab, and one received brodalumab. The median FIT level and fCal level was 0 ng/mL [interquartile range (IQR), 19.5 ng/mL] and 39.4 mg/kg (IQR, 304 mg/kg) at baseline. Thereafter, the median FIT level and fCal level on 3 months after initiating antibody therapy increased to 19 ng/mL (IQR, 15 ng/mL) and 222 mg/kg (IQR, 71 mg/kg), respectively. Endoscopic findings before administration showed mild edema in one patient and mild redness in one patient, and thereafter these two patients showed unchanged endoscopic findings, and one patient showed new mild edema and another patient showed new mild redness after administration. The number of mononuclear cells infiltrating in the mucosa significantly increased with antibody administration. Microbial community analysis did not show alteration in alpha diversity after antibody administration. Proteobacteria was increased after the administration.

Conclusions: Although no one occurred clinical symptoms after IL-17 inhibition in this case series, blocking IL-17 signals altered intestinal homeostasis toward mucosal inflammation.