Although aspartate aminotransferase (AST) is a serum marker of hepatocellular damage in chronic hepatitis, it is difficult to interpret very high AST levels with concurrent low alanine aminotransferase (ALT) levels. Macro-AST is an immunoglobulin-AST complex that can present as aberrant high enzymatic activity without significant inflammation in the liver. Two patients with chronic hepatitis B presented with disproportionate AST elevations. Their plasma samples were precipitated with polyethylene glycol (PEG) and stored at 4°C for macro-AST determinations. In Case 1, PEG precipitation showed 100% removal of AST activity, and refrigerated storage resulted in a ~70% decline over seven days, confirming macro-AST. In Case 2, both tests showed minimal changes, suggesting that macro-AST was unlikely. The AST levels normalized after antiviral therapy, suggesting immune-active hepatitis as the probable cause, but the other contributing factors could not be completely excluded. The abrupt decrease in AST activity after PEG precipitation and during refrigeration storage suggests that relatively high AST values compared to ALT might be attributed to the presence of macro-AST.These non-invasive methods for detecting macroenzymes might help the patient avoid unnecessary further work-ups.

Hepatic portal venous gas (HPVG) may suggest an ominous pathology that requires immediate attention because it is frequently associated with life-threatening conditions such as mesenteric ischemia and bowel necrosis. Therefore, early recognition and accurate differential diagnosis are crucial for timely intervention. This paper presents a 78-year-old female who developed extensive HPVG with a fatal clinical course, ultimately resulting in death despite intensive medical management.

Background/Aims: Sufficient sedation is important when performing an endoscopic submucosal dissection (ESD) for an esophageal squamous cell carcinoma (ESCC), and dexmedetomidine (DEX) is being increasingly used. ESD is often performed in elderly patients and those with comorbidities. Therefore, adverse events (AEs) in the circulatory and respiratory systems remain a clinical concern.Despite this, limited data exist on these AEs, so this study was conducted to investigate this issue. Methods: This single-center retrospective study included 526 patients who underwent ESD for ESCC under DEX-based sedation from 2016 to 2023. The study assessed the incidence of AEs in circulatory and respiratory systems, as well as the risk factors associated with these events. Various clinical factors, including the Prognostic Nutritional Index (PNI), were analyzed as candidates. Results: Circulatory AEs occurred in 55 cases (10.5%), including bradycardia (7.2%) and hypotension (4.2%). Univariate and multivariate analyses revealed significant associations of lower PNI (<45) and prolonged procedure time with circulatory AEs (p=0.023 and p=0.008, respectively). Respiratory AEs occurred in 12 cases (2.3%), including respiratory depression (1.0 %) and post-ESD pneumonia (1.5 %) with one fatal case (0.2 %). An analysis of respiratory AEs showed that the elderly (≥80 years) and lower PNI were significant in univariate analysis but not in multivariate analysis (both p=0.07). Conclusions When performing ESD for ESCC under DEX-based sedation, special caution is needed for patients with lower PNI and the elderly, who are more likely to experience circulatory or respiratory complications.

Colorectal cancer (CRC) is one of the most common malignancies worldwide and the second leading cause of cancer-related death.In South Korea, the incidence of CRC has increased alongside rapid socioeconomic development and westernized lifestyles, but it has recently shown a gradual decline, largely due to the National Cancer Screening Program (NCSP). The NCSP, first launched in 1999 and expanded in 2004 to include CRC screening, has reduced the incidence and mortality of colorectal cancer significantly, while improving the five-year relative survival rate. The Korean Colonoscopy Screening Pilot Study (K-COSPI) reported the feasibility, safety, and high acceptability of colonoscopy as a primary screening tool, suggesting the potential to transition to colonoscopy-based national screening. Nevertheless, challenges persist in increasing participation and maintaining high-quality performance because the adenoma detection rate remains a critical indicator of screening effectiveness. Continuous efforts to strengthen public awareness, enhance the quality control of colonoscopy, and develop evidence-based, risk-stratified screening strategies will be essential for sustaining and advancing this exemplary public health achievement.

Despite the advances in biological and small-molecule therapies, a substantial proportion of patients with inflammatory bowel disease (IBD) experience multiple treatment failures, constituting difficult-to-treat IBD with remission rates plateauing at 30–50%.Advanced combination therapy (ACT), defined as the concomitant use of two advanced therapies with distinct mechanisms of action, has become a strategy to overcome this therapeutic ceiling. This review aims to synthesize the rationale, clinical evidence, safety profile, and practical implementation strategies of ACT in IBD. A narrative review of randomized controlled trials (RCTs), meta-analyses, and real-world observational studies evaluating ACT in IBD was performed, focusing on the mechanistic rationale, efficacy outcomes, safety data, and clinical application strategies. ACT is supported by pharmacokinetic synergy (reduced immunogenicity and improved drug exposure) and pharmacodynamic complementarity (simultaneous blockade of multiple inflammatory pathways). Proof-of-concept RCTs, including VEGA and EXPLORER, along with meta-analyses, revealed higher clinical and endoscopic remission rates with ACT than with monotherapy in refractory populations. The safety profiles are generally comparable to monotherapy, but regimen-specific heterogeneity exists. Although vedolizumab- or ustekinumab-based combinations show favorable long-term safety, regimens including natalizumab or JAK inhibitors warrant caution and close monitoring. Detailed clinical strategies include induction-bridge approaches with JAK inhibitors, safety-anchor strategies with gut-selective agents, mechanistic complementarity strategies for treatment failures, and double-indication strategies for extraintestinal manifestations. ACT is a promising rescue strategy for D2T IBD with encouraging efficacy and acceptable safety. Future research should focus on large-scale RCTs and biomarker-driven strategies to optimize patient selection and treatment protocols for ACT.

Biliary tract cancer (BTC), encompassing intrahepatic and extrahepatic cholangiocarcinoma as well as gallbladder cancer, represents a heterogeneous group of malignancies characterized by an aggressive clinical course and poor prognosis. Systemic chemotherapy with gemcitabine plus cisplatin has remained the standard first-line treatment for more than a decade because most patients are diagnosed at an advanced or unresectable stage, but the associated survival benefit is limited. Recent therapeutic advances have been driven by the integration of immunotherapy and molecularly targeted approaches. Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) have shown clinically meaningful activity, particularly in combination with cytotoxic chemotherapy, and are increasingly being incorporated into first-line treatment strategies for advanced BTC. Concurrently, comprehensive molecular profiling has revealed substantial genomic heterogeneity and identified actionable alterations, including fibroblast growth factor receptor 2 (FGFR2) fusions, isocitrate dehydrogenase 1 (IDH1) mutations, and human epidermal growth factor receptor 2 (HER2) amplification, enabling the development of precision targeted therapies for selected patient populations. Despite these advances, the therapeutic responses to immunotherapy and targeted agents remain highly variable, and robust predictive biomarkers have yet to be established. Accordingly, optimizing patient selection by integrating molecular and immunologic characteristics has become a critical objective for improving clinical outcomes. This review provides an overview of the recent progress in immunotherapy and targeted therapy for BTC, focusing on pivotal clinical trials, therapeutic efficacy, current limitations, and future perspectives for personalized treatment strategies.

Chronic hepatitis B remains a major global health challenge despite the advances in antiviral therapy. Although hepatitis B surface antigen (HBsAg) seroclearance is considered a functional cure, liver-related complications, particularly hepatocellular carcinoma, may still occur after viral clearance. This residual risk reflects the lasting impact of host and liver factors rather than ongoing viral activity. Conventional prediction models have attempted to stratify the residual risk after a functional cure but remain limited in their ability to guide individualized management. Recent advances in machine learning have enabled more precise risk stratification by capturing complex host-driven determinants of the long-term outcomes. These approaches support a shift from uniform surveillance toward risk-adaptive monitoring strategies. Nevertheless, post-cure management is emerging as a new clinical priority as more patients achieve a functional cure. Therefore, a functional cure should be viewed not as the end of the disease, but as the beginning of a phase requiring personalized risk assessment and surveillance.