Introduction

Ulcerative colitis (UC) is an idiopathic chronic inflammatory bowel disease. The current goal of UC treatment is to modify the natural history of the disease and prevent long-term bowel damage and subsequent disability by using appropriate therapy and monitoring at appropriate intervals.
In 2015, the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) committee proposed a treat-to-target (T2T) approach and recommended that the therapeutic target in UC should be both clinical and patient-reported outcomes (PRO) remission as well as endoscopic remission with Mayo endoscopic subscore (MES) 0 and 1. However, in STRIDE II, only MES 0 of endoscopic remission is the treatment target and histologic remission is also considered to be a treatment target. Previous studies have demonstrated that patients who achieve an MES of 0 are more likely to have a longer duration of clinical remission than patients without endoscopic remission. Additionally, several studies have shown that histologic remission is a distinct treatment target from endoscopic remission in UC and better predicts clinical remission.
The current treatment target of UC is endoscopic remission with MES 0 as well as clinical remission, but distinguishing between MES 0 and MES 1 is difficult. In our previous study, we demonstrated that histologic activity predicts clinical relapse in UC patients with MES 0 or 1. However, there is no study on whether histologic remission can predict another target, such as endoscopic remission. The aim of this study was to evaluate whether histologic activity can predict the maintenance of endoscopic remission in UC patients with MES 0 or 1.

Aims & Methods

The aim of this study was to evaluate whether histologic activity can predict the maintenance of endoscopic remission in UC patients with Mayo endoscopic subscore (MES) 0 or 1. Four hundred ninety-two UC patients who underwent histologic evaluation at Samsung Medical Center from January 2018 to December 2020 were included in this study. Patients were divided into two groups based on their histologic activity: histologic remission and active. Endoscopic activity was assessed during follow-up, and the primary outcome was endoscopic remission according to histologic activity. Endoscopic remission was defined as an MES of 0, while histologic remission was defined as a Geboes score of < 3.1.

Results

Among the 492 patients, 435 were evaluated for endoscopic activity during the first colonoscopic follow-up, and 146 patients were evaluated during the second follow-up. The median time for the first follow-up colonoscopy was 27.3 months. The histologic active group at index colonoscopy was more likely to experience endoscopic relapse than the histologic remission group (hazard ratio (HR)= 1.63, P < 0.001). In subgroup analysis in patients without clinical relapse, the histologic active group was still more likely to experience endoscopic relapse than the histologic remission group (HR = 1.53, P = 0.030).

Conclusion

The patients who achieve histologic remission are more likely to maintain endoscopic remission compared to those with histologic activity.

References

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2. Magro F, Gionchetti P, Eliakim R, Ardizzone S, Armuzzi A, Barreiro-de Acosta M, et al. Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1: Definitions, Diagnosis, Extra-intestinal Manifestations, Pregnancy, Cancer Surveillance, Surgery, and Ileo-anal Pouch Disorders. J Crohns Colitis. 2017;11(6):649-70.
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6. Turner D, Ricciuto A, Lewis A, D'Amico F, Dhaliwal J, Griffiths AM, et al. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology. 2021;160(5):1570-83.

Introduction

HBV infection is a critical global health issue and the leading cause of cirrhosis and hepatocellular carcinoma (HCC) with its mechanisms still not fully understood. Despite existing several HCC biomarkers, challenges such as low sensitivity and tumor heterogeneity hinder early detection, highlighting the need for further exploration of mechanisms and new diagnostic markers.

Aims & Methods

In this study, we conducted an integrated multi-omics study of HCC GWAS, TCGA-LIHC, GTEx, and HPA data, in order to identify pathogenic genes and serum markers for HBV-associated HCC. The expression of candidate genes or serum markers were then evaluated in HCC liver tissues or serum. In vitro and in vivo cellular functional experiments were performed to determine their roles in tumor progression.

Results

Our findings revealed that the ATF6B-APOC2-CD36 axis derived growth and metastasis in HBV-associated HCC. Mechanistically, HBV induced ATF6B expression via the endoplasmic reticulum stress pathway. Then ATF6B bound to the APOC2 promoter region, thereby enhancing APOC2 expression. APOC2 further interacted with CD36 to activate the Wnt/β-catenin signaling pathway, promote EMT and consequently facilitate the growth and metastasis of liver cancer. Moreover, serum APOC2 significantly increased in HBV-related HCC patients and when combined with PIVKA-II shown high diagnostic value for AFP-negative HBV-related HCC.

Conclusion

Our findings demonstrated that the ATF6B-APOC2-CD36 axis contributes to HCC progression and serum APOC2 offers diagnostic potential for AFP-negative HBV-related HCC patients. These findings may advance molecular understanding, early diagnosis, and treatment of HBV-related HCC.

Introduction

Primary sclerosing cholangitis (PSC) is a major type of autoimmune cholestatic liver disease with unknown etiology, characterized by cholestasis, abnormal biliary epithelial homeostasis, biliary tract fibrosis and consequently liver dysfunction^1,2. Notably, PSC further elevates the risk of developing cholangiocarcinoma³. Investigating the underlying causal factors could contribute to the development of novel therapeutic strategies, thereby mitigating the burden on public health systems imposed by these conditions.
Altered bile acid (BA) homeostasis is an intrinsic facet of cholestatic liver diseases. The toxicity of bile acids is associated with the severity of cholestatic diseases^4,5. Among all BA components, hydrophobic BAs such as chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA)⁶ are considered the main toxic components to the bile duct epithelium and hepatocytes. Besides, glycochenodeoxycholic acid (GCDCA) has been used to model BA toxicity both in vivo and in vitro⁷. The clinical usefulness of plasma BA in cholestatic diseases was studied via BA profiling in cholangitis cohorts, and the clinical utility was analysed^4,8. Nevertheless, no large-scale epidemiology studies have identified the causal relationship between individual components of BA and the pathogenesis of cholangitis, especially the sequence between changes in BA composition and disease onset.
In this study, we extracted summary statistics of 32 plasma BA components from the largest metabolome GWAS dataset to date⁹ as exposures and performed two-sample MR using 2 datasets of PSC as outcomes, followed by reverse MR, to assess the causal relationship between BAs and the pathogenesis of this disease.

Aims & Methods

We aimed to identify causal bile acid components on PSC using mendelian randomization. Summary statistics for primary sclerosing cholangitis were retrieved from European Bioinformatics Institute and FinnGen Consortium, and plasma bile acid components data were obtained from European Bioinformatics Institute. BA profiles of PSC patients by GC-MS were retrieved from published researches. Statistical analyses used the inverse variance weighted(IVW), weighted median(WM), maximum likelihood(ML) and MR-Egger algorithm, followed by various sensitivity analyses and reliability evaluation.

Results

Plasma level of glycochenodeoxycholate glucuronide(GCDCG) is negatively correlated with primary sclerosing cholangitis (IVW: OR=-0.12, p=0.0269 in EBI dataset, OR=-0.38, p=0.0299 in FinnGen dataset). No reverse causal effect was identified(IVW: p=0.7067 in EBI dataset, p=0.5158 in FinnGen dataset). GCDCG was decreased in bile of patients with PSC compared with healthy controls (logFC=-2.09, p=0.010).

Conclusion

Our findings provide evidence regarding the risk of primary sclerosing cholangitis for individuals with low level of plasma glycochenodeoxycholate glucuronide, and targeting the transformation of glycochenodeoxycholate into its glucuronide may be a novel therapeutic strategy to primary sclerosing cholangitis.

References

1. Dyson JK, Beuers U, Jones DEJ, et al. Primary sclerosing cholangitis. Lancet 2018;391(10139):2547-2559.
2. Levy C, Manns M, Hirschfield G. New Treatment Paradigms in Primary Biliary Cholangitis. Clin Gastroenterol Hepatol 2023;21(8):2076-2087.
3. Tham EKJ, Lim RY, Koh B, et al. Prevalence of Chronic liver disease in Cholangiocarcinoma: a Meta-Analysis. Clin Gastroenterol Hepatol 2024.
4. Mousa OY, Juran BD, McCauley BM, et al. Bile Acid Profiles in Primary Sclerosing Cholangitis and Their Ability to Predict Hepatic Decompensation. Hepatology 2021;74(1):281-295.
5. Perreault M, Białek A, Trottier J, et al. Role of glucuronidation for hepatic detoxification and urinary elimination of toxic bile acids during biliary obstruction. PLoS One 2013;8(11):e80994.
6. Hofmann AF. The continuing importance of bile acids in liver and intestinal disease. Arch Intern Med 1999;159(22):2647-58.
7. Du Y, Khandekar G, Llewellyn J, et al. A Bile Duct-on-a-Chip With Organ-Level Functions. Hepatology 2020;71(4):1350-1363.
8. Tietz-Bogert PS, Kim M, Cheung A, et al. Metabolomic Profiling of Portal Blood and Bile Reveals Metabolic Signatures of Primary Sclerosing Cholangitis. International Journal of Molecular Sciences 2018;19(10):3188.
9. Chen Y, Lu T, Pettersson-Kymmer U, et al. Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases. Nature Genetics 2023;55(1):44-53.

Introduction

The management of obesity is often complicated by associated comorbidities such as type 2 diabetes, hypertension and hyperlipidaemia—all of which contribute to significant polypharmacy. High pill burden is linked to reduced adherence, increased healthcare costs, and lower quality of life. While Endoscopic Sleeve Gastroplasty (ESG) has been established as a minimally invasive intervention for weight loss, its impact on medication use remains underexplored. This study aims to evaluate changes in medication burden following ESG in a real-world cohort, with a focus on the potential for pharmacological de-escalation alongside weight loss.

Aims & Methods

We conducted a retrospective review of 236 patients who underwent ESG at Singapore General Hospital between November 2020 and December 2025. All procedures were performed by a single experienced endoscopist using a U-shaped suturing pattern. The primary outcome was change in medication burden, defined as the total number of prescribed medications at baseline, 6 months, and 12 months following ESG. Data on medication count were collected from electronic medical records, including all chronic medications prescribed for obesity-related comorbidities.

Results

At baseline, 17.8% of patients were on one or more oral anti-diabetic medications, 2.6% were on insulin, 30.9% were taking antihypertensives, and 22% were on lipid-lowering therapy. At 6 months post-ESG, the proportion of patients on anti-diabetic medications decreased to 15.2%, and insulin use dropped slightly to 2.1%. Anti-hypertensive use declined to 20.8%, and lipid-lowering therapy was reduced to 17.1%. By 12 months, further reductions were observed: 12.7% of patients remained on anti-diabetic medications, only 1.4% were on insulin, and use of anti-hypertensives and lipid-lowering agents fell to 20.8% and 18.8%, respectively.
The total number of medications per patient decreased significantly over time. At baseline, patients were on an average of 1.36 medications targeting diabetes, hypertension, and hyperlipidemia. This declined to 0.61 medications at 6 months and 0.59 at 12 months, corresponding to mean reductions of 0.75 (95% CI: 0.42–1.07, p < 0.001) and 0.77 (95% CI: 0.46–1.08, p < 0.001), respectively. These reductions were consistent across all major cardiometabolic drug classes.

Conclusion

In addition to driving meaningful weight loss, ESG contributes to a measurable reduction in medication burden for obesity-related comorbidities. These findings support the broader role of ESG in promoting pharmacologic de-escalation, potentially improving long-term adherence and quality of life in patients with obesity.

Disclosure

NIL