Introduction

Esophageal variceal bleeding is a serious and fatal complication of cirrhosis. Currently, efficient noninvasive monitoring strategies are lacking. By applying artificial intelligence (AI) to computed tomography (CT) imaging, we developed an innovative tool to meet clinical needs.

Aims & Methods

This is an ambispective cohort study conducted at West China hospital between April 2021 and December 2021, patients underwent endoscopy and enhanced CT were registered. Furthermore, 97 patients with radiomic and hepatic venous pressure gradient data were enrolled from a portal hypertension database. High-risk esophageal varices (HREV) were defined as either moderate-severe varicose (HREV-1) or EV requiring intervention (HREV-2). Deep learning was used to develop segmentation and EV quantification models. The EV bleeding prediction model was established using least absolute shrinkage and selection operator (LASSO) regression and logistic regression analysis. The area under the curve (AUC) was calculated for efficiency evaluation. This trial is registered with the Chinese Clinical Trial Registry (ChiCTR2300069865) and is completed.

Results

A total of 2291 patients in the retrospective (n=780) and prospective (n=1511) cohorts were included. The internal and external validation cohort AUCs were 0.976 and 0.951 for EV vs. non-EV, 0.986 and 0.951 for HREV-1, and 0.978 and 0.898 for HREV-2, respectively. We found that volume (p=0.0348) and AI-10 (p=0.0196) were closely related to portal pressure. We further analyzed the AI features and bleeding events for patients with cirrhosis in the retrospective (n=254) and prospective (n=569) cohorts and applied the EV bleeding prediction model (validation cohort AUCs of 0.669, 0.701 and 0.705 at 1, 3, and 6 months, respectively), which was not inferior to that of endoscopic signs (p > 0.05).

Conclusion

Enhanced CT assisted by AI is a promising noninvasive strategy for quantifying EV, recognizing HREV and predicting short-term bleeding risk and has the potential to replace simple gastroscopy for diagnosis or monitoring. This approach could decrease unnecessary gastroscopy to some extent.

Disclosure

The authors have declared no competing interests.

Clinical Case Summary

A 13-year-old boy presented with abdominal distention, recurrent hypoglycemia, and self-resolving jaundice. Clinical examination revealed growth retardation and hepatosplenomegaly. Blood work revealed anemia, thrombocytopenia, elevated aspartate and alanine transaminase levels, and raised plasma cholesterol and triglycerides. Ultrasound showed an enlarged liver with surface irregularity, splenomegaly, and a dilated portal vein. Etiological work-up for cirrhosis was positive for hepatitis B (HBV) surface antigen (HbsAg) and antibodies for HBV core and envelope antigens (anti Hbc, antiHbe) but an undetectable HBV DNA level. HBV was considered to be an unlikely cause of cirrhosis due to the young age of the patient, hence further metabolic and genetic work-up was done. Tests for Wilson’s and autoimmune liver disease were negative. Liver biopsy revealed a distorted lobular architecture with nodules, thin septae, and portal fibrosis. Hepatocytes showed marked swelling and pyknotic nuclei, and negative HbsAg immunostaining. Molecular analysis revealed a novel mutation in the exon 3 of the PHKG2 gene (c.98G>T, p.Gly33Val). The patient was diagnosed with cirrhosis due to GSD IXc with inactive chronic hepatitis B. His symptoms resolved with an optimized diet of corn starch, high-protein and vitamin supplementation. The importance of liver transplantation was also discussed with the family.

Introduction

Gastric cancer is the 5^th most common cancer globally(1). Europe's Beating Cancer Plan recognises the urgent need for a gastric cancer screening strategy(2). One promising approach, outlined in the Maastricht VI/Florence consensus report, suggests integrating screening modalities for gastric cancer, such as gastroscopy with colorectal cancer screening (3). This method holds the potential for cost-saving benefits through combined screening efforts (4).

Aims & Methods

We aimed to determine the prevalence of preneoplastic and neoplastic lesions in a high-risk age group, in those who underwent gastroscopy at the time of colonoscopy. Our secondary aims were to determine a)the quality of endoscopy performed and b) the endoscopic burden for pathology that required follow-up.
This was a single-centre review and audit of key performance indicators in a colorectal cancer screening centre. The age group targeted was 50-74, i.e. the target group for colon cancer screening in Europe. We included those undergoing colonoscopy for polyp surveillance or as part of the national colon cancer screening programme. Participants with red flag symptoms (iron deficiency anaemia, weight loss, dysphagia), family history of gastric cancer, established diagnosis of Barrett’s, intestinal metaplasia, dysplasia or who had a gastroscopy in the last 3 years were excluded. The sample size required for a 95% confidence interval with a presumed positivity rate of 5-7% was 101. Descriptive statistics, correlations and associations were examined using Stata software.

Results

101 patients were included; the median age was 59;38% were male. Indications for gastroscopy included abdominal pain (45%), chronic reflux (37%), chronic dyspepsia (7%) and other (9%). All patients had a technically complete gastroscopy (D2 intubation rate 100%, retroflexion 100%), the median procedure length was 7 minutes(range 4-21). 93% of patients had a macroscopic finding at the time of gastroscopy. Findings included gastritis(chronic superficial, chemical)(60%), hiatus hernia (50%), oesophagitis (28%), duodenitis (24%), gastric body polyps (10%), Barrett’s mucosa (8%), benign gastric or duodenal ulceration(9%), Schatzki ring (4%), erosions (4%), intestinal metaplasia (IM)(1%), oesophageal candidiasis (1%) and varices (1%). 59% had biopsies taken from two topographical sites as per MAPS guidelines. On biopsy, Helicobacter pylori infection was found in 15% (15/101), 7% had intestinal metaplasia(IM); no atrophy, dysplasia or cancer was detected. In those with IM who had MAPS biopsies (5/7), all were focal IM. In those with suspected Barrett’s (n=8), 88% had biopsies taken in accordance with the Seattle protocol and the Prague classification was used in 50% of cases. Additional pathology encountered included histological evidence of antral gastritis (56%), body gastritis (53%), reflux oesophagitis (21%), Barrett’s without dysplasia (4%), duodenitis (3%), and eosinophilic oesophagitis (1%). There was no statistical difference in age (p<0.82) or gender (p<0.32)in those with preneoplastic changes on gastroscopy.

Conclusion

11% of individuals within the target age bracket exhibited a pre-neoplastic condition on gastroscopy and/or histology (i.e. gastric intestinal metaplasia, gastric atrophy or Barrett's oesophagus), a further 15% were diagnosed and treated for Helicobacter pylori infection, the leading cause of gastric cancer. Among these cases, 4-7% necessitated subsequent surveillance gastroscopy. Our findings support the role of dual endoscopic screening with quality gastroscopy as a potential strategy for gastric cancer screening.

References

1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-49. doi: 10.3322/caac.21660. Epub 2021 Feb 4.
2. Commission E. Europe's Beating Cancer Plan - Communication from the commission to the European Parliament and the Council. 2021.
3. Malfertheiner P, Megraud F, Rokkas T, Gisbert JP, Liou JM, Schulz C, et al. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut. 2022.
4. Libanio D, Antonelli G, Marijnissen F, Spaander MC, Hassan C, Dinis-Ribeiro M, Areia M. Combined gastric and colorectal cancer endoscopic screening may be cost-effective in Europe with the implementation of artificial intelligence: an economic evaluation. Eur J Gastroenterol Hepatol. 2024;36(2):155-61. doi: 10.1097/MEG.0000000000002680. Epub 2023 Nov 15.

Introduction

Arsenic, a potent environmental toxin, has been widely reported to cause significant health problems, including liver damage and disturbances in the metabolic processes. One of the lesser-understood facets of arsenic toxicity is its impact on gut microbiota, the community of microorganisms living in the intestinal tract, which plays a crucial role in host metabolism and overall health. Previous studies have indicated that arsenic exposure can alter the composition of gut microbiota, potentially affecting the host’s metabolism of arsenic and exacerbating its toxic effects. Despite ongoing research, the mechanisms underlying the interaction between arsenic exposure, gut microbiota changes, and arsenic metabolism remain inadequately defined.

Aims & Methods

The primary objective of this study was to elucidate the dynamics of gut microbiota changes under varying levels of arsenic exposure and to understand how these changes affect arsenic metabolism and subsequent liver toxicity. We used C57BL/6 mice as a model system, exposing them to 0, 5, or 10 ppm sodium arsenite (NaAsO2) in their drinking water over a period of six months. We conducted a comprehensive analysis of the gut microbiota, focusing on folic acid (FA)/vitamin B12 (VB12)- and butyrate-synthesizing communities. Additionally, molecular interactions between arsenic and methionine synthase (MTR), an enzyme crucial for FA/VB12 utilization, were assessed using 3D molecular simulations and biochemical assays. The intervention model involved supplementation of FA and VB12 to evaluate their protective effects against arsenic-induced disturbances.

Results

Exposure to NaAsO2 significantly altered gut microbiota, with a notable increase in the abundance of FA/VB12- and butyrate-synthesizing microbiota. This shift was hypothesized to compensate for the disrupted utilization of these nutrients due to arsenic exposure. In higher arsenic exposure levels, however, the microbiota changes were inconsistent, suggesting a potential threshold beyond which the compensatory mechanism may be overwhelmed. Biochemical assays confirmed that arsenic binds to MTR, disrupting its function and further impacting FA/VB12 metabolism. The interaction was substantiated by SEC-UV-DAD and fluorescence-labeled arsenic studies, which demonstrated that arsenic directly interacts with MTR in both non-cellular and cellular systems. Our intervention model using FA and VB12 supplementation showed that it was possible to mitigate the disturbances in gut microbiota, restore MTR levels, enhance arsenic metabolism, and reduce liver injury.

Conclusion

This study provides significant insights into the interaction between arsenic exposure and gut microbiota. We demonstrated that changes in gut microbiota are not merely a consequence of arsenic exposure but are intricately linked to the metabolic processes affected by arsenic, particularly through the disruption of MTR function. The supplementation of FA and VB12 proved effective in blocking these disturbances, suggesting potential therapeutic strategies to combat arsenic toxicity. The findings emphasize the importance of considering gut microbiota in the management and treatment of arseniasis and underscore the complex interplay between environmental toxins, gut microbiota, and host metabolism. Future studies should focus on further delineating the specific pathways and mechanisms by which microbiota influence arsenic metabolism and exploring the potential for microbiota-targeted therapies in arsenic-related diseases.

Introduction

Crohn’s disease (CD), a variant of inflammatory bowel disease, is a complex, debilitating, chronic and relapsing disorder of the gastrointestinal tract. If poorly controlled, patients are at risk of intestinal obstruction and infection due to the formation of strictures, fistulae and narrowing of the intestinal lumen, often requiring surgical intervention. As the precise aetiology remains unclear, current treatments for CD are limited. An altered composition of native gut microbiota may play a role in CD pathogenesis, with recent faecal microbiota transplantation (FMT) studies revealing variable therapeutic efficacy in CD management. Orally administered Emu Oil, derived from Emu adipose tissue, has demonstrated anti-inflammatory and reparative properties in models of intestinal disease.

Aims & Methods

The current study aimed to determine whether Emu Oil-modulated FMT could reduce disease severity and modulate the gut microbiota in a mouse model of trinitrobenzene sulfonic acid (TNBS)-induced Crohn’s-like colitis. Female ARC(s) mice were assigned to FMT donor (n=5/group) and recipient (n=10/group) groups. Donor mice were orally administered either Water (80μl), Olive Oil (OO) or Emu Oil (160μl) daily (days -7 to 0); fresh faeces were collected (days -1 to 3) and pooled per group. Recipient mice were administered TNBS (3mg; day 0) and donor faecal supernatant (120μl; day 3) intrarectally and euthanised on day 6. Daily bodyweight and disease activity index (DAI), colonoscopically-assessed disease severity, organ weights, intestinal permeability (fluorescein isothiocyanate [FITC]-dextran uptake), histologically-assessed colonic damage (disease severity, crypt depth), intestinal barrier function (mucin-secreting cells), acute inflammation (myeloperoxidase [MPO]) and faecal microbiome (16S rRNA amplicon sequencing) were assessed. p<0.05 was considered statistically significant.

Results

TNBS induced bodyweight loss in all groups, which normalised to day 0 values on the final day of the experimental period. Daily DAI remained elevated throughout the trial in all groups; only Emu Oil FMT normalised DAI on day 6 compared with day 0 (p<0.05). TNBS increased colonoscopically-assessed disease severity scores (p<0.05), with no significant Emu Oil nor OO FMT effect. Emu Oil FMT decreased liver weights and increased small intestinal weights relative to bodyweight, reduced histologically assessed disease severity and increased colonic mucin counts compared with Water and OO FMT (p<0.05). The most abundant genera across all groups were Muribaculaceae, Eisenbergiella and Bacteroides; while alpha and beta diversity, taxonomic profiles, FITC-dextran, crypt depth and MPO activity remained unchanged in all treatment groups (p>0.05).

Conclusion

Emu Oil-modulated FMT improved histologically-assessed indicators of intestinal disease and barrier function, compared with Water FMT and OO FMT. Interestingly, Emu Oil-modulated FMT affected liver and small intestinal organs weights, suggesting a systemic effect in this setting of disease. Importantly, key genera across taxonomic profiles were identified, however, the microbiome and remaining disease indicators were largely unchanged between treatments. Overall, Emu Oil-modulated FMT demonstrates therapeutic potential in CD management. Future studies would benefit from a deeper assessment of the gastrointestinal microbiome through long-read whole genome sequencing to further determine the role of the microbiome in EO FMT efficacy compared with conventional FMT.

Introduction

With the recent rise in the occurrence of esophageal adenocarcinoma (EAC) in Western nations, there is an escalating worry regarding Barrett’s esophagus (BE). In contrast, Asian countries exhibit a lower prevalence of BE compared to their Western counterparts. Given the annual increase in chronic gastroesophageal reflux disease (GERD) cases, there is an expectation of a concurrent rise in the prevalence of BE. Consequently, we are embarking on a multicenter prospective study to assess the current prevalence of BE and pinpoint its risk factors in Taiwan.

Aims & Methods

Aim: to evaluate current prevalence and risk factors of Barrett's esophagus in Taiwan.
Methods: We carried out a prospective multicenter study involving consecutive outpatients who underwent upper gastrointestinal endoscopy for various upper gastrointestinal symptoms. Biopsies were taken from endoscopically suspected esophageal metaplasia (ESEM), clearly visible at least 1 cm above the gastroesophageal junction during endoscopy. The biopsy procedure involved obtaining standardized random samples, with four pieces taken every 2 cm from the four quarters of the esophagus exhibiting the ESEM lesion. BE was defined based on the histological confirmation of specialized intestinal metaplasia in the metaplastic esophageal epithelium.

Results

A total of 8925 subjects were enrolled in this study. The prevalence of BE was 2.6%. A total of 228 subjects with BE were detected among 751 ESEM subjects. Short segment BE (78.1 % , n = 178) was more prevalent than long segment BE (22.9 % , n = 50). The prevalence of GERD symptoms, erosive esophagitis (EE), and hiatal hernia (HH) was 52.5%, 27.3% and 7.85%, respectively. Multivariate analysis disclosed that old age [odds ratio (OR) = 1.59; 95% CI, 1.20-2.11; P <0.01], male gender (OR = 2.27; 95%CI, 1.65-3.11; P < 0.01),alcohol consumption (OR = 1.70, 95%CI, 1.19-2.44; P< 0.01), GERD symptoms (OR = 1.45, 95%CI, 1.10-1.92; P< 0.01), EE (OR = 1.94, 95%CI, 1.47-2.56; P< 0.01) and presence of hiatal hernia (OR = 2.49; 95%CI, 1.78-3.47; P < 0.001) were significant risk factors predicting BE.
Risk factors for Barrett esophagus: multivariable analysis.

Conclusion

The prevalence of BE was identified as 2.6%. Notably, advanced age (>50), male gender, alcohol consumption, symptoms of gastroesophageal reflux disease (GERD), erosive esophagitis, and the presence of hiatal hernia emerged as independently significant risk factors for Barrett's esophagus.

References

1. Sharma P. Barrett Esophagus: A Review. Jama. 2022;328(7):663-71.
2. Marques de Sá I, et al. The global prevalence of Barrett's esophagus: A systematic review of the published literature. United European Gastroenterol J. 2020;8(9):1086-105.
3. Chang CY, et al. Current status of Barrett's esophagus research in Asia. J Gastroenterol Hepatol. 2011;26(2):240-6.
4. Shiota S, et al. Prevalence of Barrett's Esophagus in Asian Countries: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2015;13(11):1907-18.
5. Chang CY, et al. The application of Prague C and M criteria in the diagnosis of Barrett's esophagus in an ethnic Chinese population. Am J Gastroenterol. 2009;104(1):13-20.
6. Fock KM, et al. Asia-Pacific consensus on the management of gastro-oesophageal reflux disease: an update focusing on refractory reflux disease and Barrett's oesophagus. Gut. 2016;65(9):1402-15.
7. Eusebi LH, et al. Global prevalence of Barrett's oesophagus and oesophageal cancer in individuals with gastro-oesophageal reflux: a systematic review and meta-analysis. Gut. 2021;70(3):456-63.
8. Akiyama T, et al. Alcohol consumption is associated with an increased risk of erosive esophagitis and Barrett's epithelium in Japanese men. BMC Gastroenterol. 2008;8:58.
9. Andrici J,et al. Hiatal hernia and the risk of Barrett's esophagus. J Gastroenterol Hepatol. 2013;28(3):415-31.

Introduction

Neutrophils could be recruited into liver in autoimmune hepatitis (AIH) and experimental AIH (Concanavalin A induced hepatitis), but the role of neutrophils in these kinds of immune related hepatitis has rare research to clarify. As previous reports, CD177 expressed exclusively on neutrophils, CD177⁺ neutrophils could alleviate inflammation in inflammatory bowel disease, and it could produce neutrophil extracellular traps that promote biliary atresia. However, there is no report about CD177⁺ neutrophils involved in AIH or experimental AIH.

Aims & Methods

In this study, we wanted to explore to role of neutrophils in AIH and wondered whether CD177⁺ neutrophils exert protective effect in it. We collected clinical samples of AIH patients and healthy control (HC), and established experimental AIH animal model by using Concanavalin A (ConA). Anti-Ly6G antibody was used as pretreatment to depleting neutrophils before ConA injection. Wild type (WT) and CD177 knock out (KO) C57BL/6J female mouse were used to construct different experimental AIH model. Flow cytometry analysis was used to detect the percentage of neutrophils in blood and liver. Detected serum biochemical indicators (ALT: alanine aminotransferase, AST: aspartate aminotransferase) and performed staining in liver tissues to evaluate liver injury.

Results

For AIH patients, CD177⁺ neutrophils in peripheral blood were significantly increased (P<0.05). And for immunohistochemistry (IHC), the positive areas of CD66b (a surface marker of neutrophils) and CD177 were more obvious in liver tissues of AIH patients (P<0.05). For animal experiment, we successfully established model of experimental AIH. In this model, liver injury was significant in ConA group than in normal control (NC) group, which showed prominent liver necrosis in hematoxylin-eosin (HE) staining and higher serum ALT and AST (P<0.05). Positive IHC areas of Ly6G and CD177 were more obvious in liver tissues of ConA group, which meant the increased infiltration of neutrophils. We found that distributions of neutrophils were different in different organ. Compared to NC group, the amount of neutrophils in ConA group was decreased in bone marrow and increased in peripheral blood and liver, and its increase in liver trended to be more obvious (P=0.096). So, we speculated that neutrophils mainly migrated to liver from marrow in ConA model. After depleting neutrophils, we through flow cytometry analysis to verify the depletion of neutrophils (CD11b⁺ Ly6G⁺ cells) in anti Ly6G-ConA group was thorough. HE staining showed liver injury appearances in ConA group and Ly6G isotype-ConA group were more severe than that in normal saline (NS) group and in anti Ly6G-ConA group. Similarly, ConA group and Ly6G isotype-ConA group had higher levels of serum ALT and AST than the other two groups. Finally, we used CD177 KO mouse to determine the role of CD177⁺ neutrophils in ConA model. HE staining showed the area of liver necrosis in CD177 KO-ConA group was largest. As for liver function, CD177 KO-ConA group also had the highest levels of serum ALT and AST (P<0.05), which improve that the liver injury in this group was the most severe.

Conclusion

Neutrophils involved in AIH and experimental AIH. In experimental AIH, depletion of neutrophils could alleviate liver injury, and CD177⁺ neutrophils could exert protective effect in it.