Journal of Gastroenterology and Hepatology最新文献

Circulating tumor cells (CTCs) are emerging as promising biomarkers in hepatocellular carcinoma (HCC), offering noninvasive insight into tumor biology, progression, and treatment response. Advances in enrichment and single-cell technologies have enabled the characterization of CTCs at genomic, transcriptomic, epigenetic, and proteomic levels. CTC detection correlates with tumor stage, vascular invasion, and alpha-fetoprotein levels, supporting their role in early diagnosis and staging. Specific surface markers such as epithelial cell adhesion molecule, GPC3, ASGPR, and stem cell–associated antigens like CD90 and CD133 help classify CTC subtypes with prognostic and therapeutic relevance. Mesenchymal and hybrid phenotypes, identified via epithelial-to-mesenchymal transition markers, are linked to recurrence and metastasis. Furthermore, CTCs provide a platform for companion diagnostics by reflecting mutational and resistance profiles, particularly in the context of targeted therapies and immune checkpoint inhibitors. Despite current limitations in standardization, sensitivity, and scalability, the integration of CTC analysis into clinical practice holds potential to enhance precision medicine strategies in HCC.

Chronic non-viral liver diseases (CNVLD), including alcohol-related liver disease (ALD) and metabolic dysfunction–associated steatotic liver disease (MASLD), have increased in prevalence, surpassing viral hepatitis as the main cause of hepatocellular carcinoma (HCC) in the last decade; thus, the identification of bloodstream biomarkers is essential for early diagnosis, risk stratification, and monitoring progression. This study aimed to systematically integrate and compare proteomic evidence from blood-based studies to identify differentially expressed proteins (DEPs) associated with ALD, MASLD, and HCC of non-viral etiology, to prioritize them as candidates for shared biomarkers and diagnostics for each disease. A systematic review was conducted, followed by a qualitative meta-analysis to identify DEPs bloodstream biomarkers. Biomarkers were compared across diseases to detect overlaps. Functional enrichment, network, and topological analyses were used to evaluate their biological relevance. We identified 16 diagnostic biomarkers for ALD, 53 for MASLD, and 8 for HCC. Four biomarkers were shared among ALD and MASLD, two among ALD and HCC, and two among MASLD and HCC. Functional analyses indicated platelet dysfunction and coagulation pathway alterations in ALD; lipid metabolism dysregulation in MASLD; and a combination of these processes in HCC patients. Network analysis highlighted key biomarkers with potential diagnostic and prognostic applications. The identified biomarkers reflect both shared and disease-specific molecular mechanisms in the progression of CNVLD toward HCC. Their consistent presence across independent studies supports their potential integration into diagnostic and prognostic panels, particularly in the context of the rising prevalence of ALD and MASLD worldwide.

Helicobacter pylori infection remains globally prevalent and is a major cause of chronic gastritis, peptic ulcer disease, and gastric cancer (GC). The Asia-Pacific region has the highest global burden of infection and GC mortality; however, the effectiveness of eradication therapy is increasingly being compromised by antibiotic resistance. Between 1990 and 2022, resistance to clarithromycin (CAM), metronidazole (MNZ), and levofloxacin (LVX) increased markedly from 7%, 37%, and 9% to 30%, 61%, and 35%, respectively, whereas resistance to amoxicillin and tetracycline remained low at approximately 4%. Multidrug-resistant H. pylori strains are increasingly being reported in Southeast Asia. The resistance rates among the pediatric and adolescent population in East Asia are similarly high, 37% for CAM, 51% for MNZ, and 19% for LVX, suggesting intrafamilial transmission. The key molecular mechanisms include genetic mutations in 23S rRNA, rdxA/frxA, and gyrA/gyrB, along with adaptive traits such as efflux pump activation and biofilm formation, and coccoid transformation. East Asian countries have adopted divergent strategies, including vonoprazan-based triple therapy in Japan, bismuth-containing quadruple therapy as the preferred first-line regimen in Taiwan, Hong Kong, and China, and tailored regimens based on susceptibility testing in Korea. Future directions include susceptibility-guided therapy, molecular diagnostic testing, family-based eradication, and the development of nonantibiotic therapies. Establishing regional resistance surveillance networks and integrating H. pylori management into national antimicrobial stewardship programs are essential to maintain eradication success and prevent GC. Addressing antibiotic resistance in H. pylori is an urgent public health priority, and coordinated regional strategies are required in the Asia-Pacific region.

Gastric intestinal metaplasia (GIM), a precancerous gastric lesion, represents a critical transitional stage in the Correa cascade that progresses from chronic inflammation to gastric adenocarcinoma (GAC). Emerging evidence implicates neutrophils as key orchestrators of GIM pathogenesis through multifaceted interactions within the tumor microenvironment. Therapeutic strategies targeting neutrophil activation, migration, and effector functions, including autophagy modulation and phenotypic reprogramming to an anti-inflammatory N2 state, hold promise in reversing GIM progression. This review synthesizes the current knowledge on neutrophil-mediated mechanisms and explores clinically actionable pathways for GIM reversibility.