Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease linked to fibrosis and hepatocellular carcinoma (HCC). Gut-derived lipopolysaccharide (LPS) promotes hepatic inflammation, fibrosis, and angiogenesis through toll-like receptor 4 (TLR4) signaling. This study examined the effects of rifaximin, a non-absorbable, gut-targeted antibiotic, on MASH-related liver fibrosis and early hepatocarcinogenesis, with a focus on the LPS–epiregulin–IL-8–angiogenesis axis.MASH was induced in Fischer 344 rats using a choline-deficient, L-amino acid-defined high-fat diet (CDAHFD). Rifaximin (30 mg/kg/day) was orally administered for 12 weeks. Liver histology, gene expression, intestinal permeability, LPS levels, and angiogenic markers were evaluated. Rifaximin reduced hepatic inflammation, fibrosis, hydroxyproline content, and fibrogenic gene expression. The number and size of GST-P-positive preneoplastic lesions and proliferation-related genes were decreased. Portal LPS levels and Kupffer cell activation declined, with downregulation of Lbp, Cd14, Tlr4, and inflammatory cytokines. Rifaximin decreased hepatic epiregulin and IL-8 expression, attenuated CD34-positive neovascularization, and suppressed proangiogenic gene expression, accompanied by improved intestinal barrier function and reduced gut permeability. Rifaximin mitigates MASH progression by restoring gut barrier integrity, limiting LPS translocation, and inhibiting fibrogenic and angiogenic pathways. These results suggest its potential as a chemopreventive agent in MASH-related hepatocarcinogenesis.

Efficacy of multi-hole self‑expandable metallic stents versus partially covered self‑expandable metallic stents in patients with malignant distal biliary obstruction caused by unresectable pancreatic cancer: a retrospective comparative cohort study in Japan

The creatinine-to-cystatin C ratio (CCR), a surrogate for skeletal muscle mass, may also be associated with liver fibrosis due to the strong link between sarcopenia and liver disease progression. We aimed to evaluate the utility of CCR as a noninvasive marker of liver fibrosis in metabolic-dysfunction-associated steatotic liver disease (MASLD). This retrospective study included 104 patients with biopsy-proven MASLD. CCR was calculated using serum creatinine and cystatin C levels. Liver fibrosis was staged histologically (F0–F4), and skeletal muscle mass was assessed using the skeletal muscle index (SMI) on computed tomography. Associations between CCR and liver fibrosis, SMI, and nonalcoholic fatty liver disease activity score were analyzed. ROC analysis evaluated CCR performance alone and in combination with FIB-4 and enhanced liver fibrosis (ELF) scores. CCR values were significantly lower in patients with significant fibrosis (≥F2). The AUROC of CCR for detecting ≥F2 fibrosis was 0.621 (95% CI: 0.509–0.733), with an optimal cutoff of 0.664. CCR alone yielded an AUC of 0.815 for predicting ≥F2 fibrosis. Combining CCR with FIB-4 and ELF substantially improved diagnostic accuracy, increasing the AUROC from 0.621 (CCR alone) to 0.820 for the combined model. CCR correlated positively with SMI (r = 0.451, p < 0.001). CCR is a simple, cost-effective biomarker reflecting muscle mass and liver fibrosis in MASLD. Combining CCR with established markers may enhance risk stratification and reduce the need for liver biopsy in selected cases.

Recently, endoscopic ultrasound-guided tissue acquisition (EUS-TA) has been widely used to diagnose pancreatic ductal adenocarcinoma (PDAC). The histological examination of core tissues acquired using novel biopsy needles is the primary diagnostic approach for patients with PDAC. However, in patients with early-stage PDAC, such as Stages 0 and I, EUS-TA can be challenging, and its diagnostic accuracy may be limited. This presents a clinical dilemma: The earlier that clinicians attempt to accurately diagnose PDAC, the more difficult it becomes to do so using EUS-TA. Liquid-based cytology (LBC) is a technique for preparing pathological specimens from liquefied cytology specimens by placing the collected material in a special fixative preservative fluid. LBC offers advantages, such as specimen optimization with reduced blood interference, a high cell-collection rate, and the simplicity of the procedure in the endoscopy room. The use of LBC may improve diagnostic accuracy, particularly for early-stage PDAC. Therefore, we emphasize that cytology remains a valuable tool for the endoscopic diagnosis of PDAC. In this review, we discuss the role of LBC in the endoscopic diagnosis of PDAC.

Endoscopic biliary drainage using self-expanding metal stents (SEMSs) is a standard palliative therapy for cholangitis and obstructive jaundice caused by malignant distal biliary obstruction (MDBO). Fully-covered SEMSs (FC-SEMSs) prevent tumor ingrowth and provide longer patency; however, recent advances in chemotherapy have increased stent migration due to tumor shrinkage, resulting in reduced functional patency compared with uncovered SEMSs. Partially covered SEMSs can reduce migration but are often difficult to remove after deployment. In addition, adverse events such as acute pancreatitis and cholecystitis remain a concern with FC-SEMSs. To address these limitations, Dr. Kobayashi introduced a novel porous SEMS with multiple side holes in the covering membrane (MH-SEMSs) in 2019. This design allows limited bile duct epithelial ingrowth through side holes, providing anchorage while maintaining removability. The side-hole structure may also reduce cholecystitis and pancreatitis by preserving flow through the pancreatic and cystic duct orifices. Over five years since their introduction, clinical evidence supporting MH-SEMSs has steadily increased. This review summarizes current data and explores future perspectives for MH-SEMS use in MDBO management.

Background/Objectives: The combined techniques of endoscopic sphincterotomy followed by endoscopic papillary balloon dilation (ESBD) and endoscopic sphincterotomy followed by endoscopic papillary large balloon dilation (ESLBD) have gained popularity for the endoscopic treatment of choledocholithiasis. However, the conventional approach to these procedures requires two separate devices, a sphincterotome and a balloon catheter, which can complicate and prolong the procedure. We herein evaluated a novel integrated device combining a sphincterotome and balloon catheter developed to improve the efficiency of ESBD and ESLBD. Methods: This retrospective study compared the clinical outcomes of patients with choledocholithiasis who were treated using conventional sphincterotome and balloon catheters (n = 106) and those who were treated using the integrated device (n = 54). Results: Overall complete stone removal rates (99.1% vs. 100%) and adverse event incidence (12.3% vs. 13.0%) were comparable between the two groups. However, the integrated device significantly reduced total procedure time (40 vs. 27 min, p = 0.01), use of mechanical lithotripter (50.0% vs. 22.2%, p < 0.01), total number of procedures required. Conclusions: Complete stone removal rates and safety were comparable between the two groups. However, the novel integrated device may enhance the efficiency of common bile duct stone removal through ESBD and ESLBD because it eliminates the need to prepare and exchange separate devices.