Introduction

Increased intestinal permeability, or leaky gut, is a condition where the gut's epithelial barrier is compromised, allowing bacteria and toxins to enter the blood stream. In liver cirrhosis, this can exacerbate liver damage and accelerate disease progression by perpetuating inflammation and immune system activation. Accurate assessment of this dysfunction is critical to the management of cirrhotic patients, but traditional methods such as serum markers and indirect assays often lack specificity and sensitivity.
Confocal laser endomicroscopy (CLE) is an advanced imaging technique that provides real-time, high-resolution visualisation of the gastrointestinal tract at the cellular and subcellular levels. CLE is used to diagnose leaky gut by directly observing disruptions in the intestinal mucosa. It integrates a confocal microscope within an endoscope, enabling in vivo histology-like imaging during routine endoscopic examinations.

Aims & Methods

We aimed to use confocal laser microendoscopy (CLE) in the diagnosis of intestinal barrier dysfunction by direct observation of the intestinal mucosa, in patients with liver cirrhosis. CLE (Cellvizio, Mauna Kea Technologies) was performed in the second part of the duodenum following intravenous administration of 2.5 – 5 mg of fluorescein in 58 patients with liver cirrhosis of various aetiologies. These patients were undergoing routine endoscopic surveillance or therapeutic intervention for oesophageal varices. The study cohort consisted of 39 men (61.9%) and 19 women (30.2%), with a mean age of 53.9 ± 14.0 years. We collected and analysed the most recent results of hepatic venous pressure gradient (HVPG), liver stiffness measurement (LSM), and fibrosis index for liver fibrosis (Fib-4). A Watson score of 1 indicates normal barrier function, while a Watson score of 2 indicates impaired barrier function. Data are given as mean± standard deviation, statistical analysis included Chi-square tests and Student’s t-tests, with a significance level set at p<0.05. NS=not significant.

Results

We observed a gradation of intestinal barrier dysfunction that correlated with the severity of liver cirrhosis. Specifically, of the 35 patients with Child-Pugh A cirrhosis, 18 (51.4%) had a Watson score of 2. In the group of 14 patients with Child-Pugh B cirrhosis, 9 (64.3%) had a Watson score of 2 and of the 9 patients with Child-Pugh C cirrhosis, 8 (88.9%) had a Watson score of 2, further underscoring the trend of increasing intestinal barrier dysfunction with increasing liver disease severity (p<0.05). In contrast, no significant differences in hepatic venous pressure gradient (HVPG) were observed between patients with Watson score 1 (16.8 ± 6.2 mmHg) and Watson score 2 (17.2 ± 6.2 mmHg, p NS). Similarly, liver stiffness measurements (LSM) showed no statistical difference between patients with Watson score 1 (39.0+/-23.7 kPa) and those with score 2 (40.2 ± 22.9 kPa) (p NS)=. Similarly, Fib-4 was 4.5 +/-3.1 in patients with Watson score 1 and 5.7+/-3.6 in patients with Watson 2 (p NS).

Conclusion

The findings suggest an association between the severity of liver cirrhosis and impaired intestinal barrier function as assessed by CLE. This impairment does not correlate with changes in haemodynamic parameters or liver fibrosis. The CLE promises to provide accurate and immediate diagnostic data and to improve our understanding of the pathophysiological changes in the gut associated with liver cirrhosis. Further research is needed to explore the mechanisms linking the severity of cirrhosis to intestinal barrier dysfunction and its clinical implications.

Disclosure

No conflict of interest to declare

Introduction

Steatotic liver disease (SLD) encompasses a spectrum of conditions, including metabolic dysfunction-associated SLD (MASLD), alcohol-related liver disease (ALD), and the overlapping category of MetALD. SLD affects more than a third of adults globally, but the majority remain undiagnosed, partially due to its lack of symptoms and limited awareness among patients and physicians. Adults undergoing screening colonoscopy, typically aged ≥50 years, represent a key population for targeted SLD detection, as they have a higher prevalence of cardiometabolic risk factors and is already engaged with preventive healthcare.

Aims & Methods

We examined 610 consecutive individuals aged ≥50 years with no known history of chronic liver disease who were referred for a colonoscopy for colorectal cancer screening. The protocol included sonographic assessment of liver steatosis and point shear wave elastography (pSWE) for liver fibrosis quantification, anthropometric measurements, biochemistry, medical history and alcohol intake evaluation. From the collected data, non-invasive fibrosis scores were calculated and used for aetiological and risk stratification.

Results

A total of 543 patients were included in the final analysis, after excluding patients with an invalid pSWE measurement (5.3%, n=29) and then excluding patients with incomplete results (n=38). The median age was 64 years (IQR 57-70) and 54.0% were male. The median BMI was 28.7 kg/m² (IQR 25.8–31.4) in males and 28.3 kg/m² (IQR 24.2-31.5) in females. SLD was identified in 63.4 % (n=344) of participants. Elevated liver stiffness (pSWE ≥ 1.30 m/s) was found in 26.9 % (n=146), and 4.8% (n=26) had values ≥1.70 m/s, suggestive of compensated advanced chronic liver disease. Among patients with pSWE ≥ 1.30 m/s, MASLD was the predominant aetiology (69.9%, n=102), followed by MetALD (15.8%, n=23), ALD (1.4%, n=2), cryptogenic (11.6%, n=17) and other etiologies (1.4%, n=2). Preselection using EASL-EASD-EASO criteria (i.e. presence of type 2 diabetes or central obesity plus ≥1 cardiometabolic risk factor and elevated liver enzymes) would have detected 365 at-risk individuals (67.2% of the cohort) of whom 55.9% (n=204) had a FIB-4 index ≥1.30. This approach would have identified only 30.4% (n=38) of all the patients with MASLD/MetALD with elevated liver stiffness (n=125).

Conclusion

Opportunistic screening for SLD in patients undergoing screening colonoscopy could be a useful strategy for detecting asymptomatic and potentially progressive liver disease. This approach identified a high prevalence of SLD (63.4%) and elevated liver stiffness (26.9%) in this population, primarily due to MASLD and MetALD. The integration of ultrasound and elastography added minimal burden to the existing workflow while enabling early risk stratification without the need for additional patient visits or referrals.

References

1 Tacke F, Horn P, Wong VWS, Ratziu V, Bugianesi E, Francque S, et al. EASL–EASD–EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). Journal of Hepatology [Internet]. 2024 Jun 7;81(3):492–542.
2 Lazarus JV, Miralles-Sanchez JE, Agirre-Garrido L, Brachowicz N, Nicolàs A, Armenta A, et al. A call to action to address the steatotic liver disease public health threat in Barcelona. The Lancet Regional Health - Europe [Internet]. 2025 Mar 22;52:101272.
3 Barr RG, Wilson SR, Rubens D, Garcia-Tsao G, Ferraioli G. Update to the Society of Radiologists in Ultrasound Liver Elastography Consensus Statement. Radiology [Internet]. 2020 Jun 9;296(2):263–74.

Introduction

ESSENCE (NCT04822181) is an ongoing 247-week Phase 3, randomised, placebo-controlled trial evaluating the effect of the glucagon-like peptide-1 analogue, semaglutide 2.4 mg subcutaneous once weekly (OW) in participants with non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH). We report the baseline characteristics of the randomised participants.

Aims & Methods

Following a 14-week screening phase, 800 participants (part 1) of 1200 planned (part 2) with MASH and fibrosis stages 2/3 (F2/F3) were randomised 2:1 to receive semaglutide 2.4 mg subcutaneous OW or placebo OW added to standard of care. In part 1, the two primary endpoints at 72 weeks are resolution of steatohepatitis and no worsening of liver fibrosis, and improvement in liver fibrosis and no worsening of steatohepatitis. Based on a central pathologist evaluation, inclusion criteria were histological presence of steatohepatitis stages F2/F3 per the Nonalcoholic Steatohepatitis Clinical Research Network classification, and a non-alcoholic fatty liver disease activity score (NAS) of ≥ 4, with a score of ≥ 1 in steatosis, lobular inflammation and hepatocyte ballooning.

Results

800 participants (250 F2; 550 F3) were randomised. Mean (SD) age was 56 (11.6) years; 57.1% were female; ≥ 99% had ≥ 1 cardiometabolic risk factor(s) in accordance with the metabolic dysfunction-associated steatotic liver disease (MASLD) definition. Mean (SD) NAS was 5.05 (0.95), and higher in F3 versus F2 (5.11 [0.95] vs 4.92 [0.93], respectively). Notably, participants with a higher NAS had more cardiometabolic risk factors for MASLD (52.9% with NAS ≥ 5 vs 45.3% with NAS 4). Similarly, a greater proportion of participants with F3 had all five cardiometabolic risk factors versus F2 (52.9% vs 44.8%, respectively). Although cardiometabolic comorbidities were highly prevalent, 44.5% of participants did not have type 2 diabetes (T2D), and 27.3% did not have obesity. Normal liver transaminases were observed in 26.3% of participants (28% F2; 26% F3). Mean (SD) FibroScan liver stiffness was 12.8 (6.9) kPa, and values of < 8 kPa were observed in 15.3% of participants. Mean (SD) controlled attenuation parameter value was 329 (46) dB/m; mean (SD) enhanced liver fibrosis (ELF) score was 10.0 (1.0), and 43.5% of participants had an ELF score of < 9.8. Overall, 8.8% and 9.0% of participants with/without T2D did not meet any of the following non-invasive criteria: Fibrosis-4 index ≥ 1.3, vibration-controlled transient elastography ≥ 8.1, or ELF ≥ 9.8, and more participants with F2 (14.7–16.4%) did not meet these criteria versus F3 (4.5–6.7%).

Conclusion

The ESSENCE baseline population includes participants with significant fibrosis (F2 and F3) and approximately 91% of the trial population had ≥ 1 positive diagnostic non-invasive test. Cardiometabolic risk factors were found in ≥ 99% of participants, and in increased numbers in those with higher NAS and fibrosis stages.
This is an encore of an abstract that will be presented for the first time at the European Association for the Study of the Liver (EASL) Congress, 5–8 June 2024, Milan, Italy.

Disclosure

The ESSENCE trial is funded by Novo Nordisk A/S.
PNN: reports grants from Novo Nordisk, and has received consulting fees from Novo Nordisk, Boehringer Ingelheim, Gilead, Intercept, Poxel Pharmaceuticals, Bristol Myers Squibb (BMS), Pfizer, Sun Pharma, Madrigal and GSK. PNN also reports honoraria as a speaker for Novo Nordisk and AiCME; support for attending meetings for Novo Nordisk; and participation on an advisory board for Novo Nordisk, Boehringer Ingelheim, Gilead, Intercept, Poxel Pharmaceuticals, BMS, Pfizer, Sun Pharma, Madrigal and GSK.
EB: served as a consultant or advisory board member for Boehringer Ingelheim, Gilead, Intercept, Merck, Novo Nordisk, Pfizer, ProSciento, and as a speaker for Gilead, Intercept, Merck, Novo Nordisk and Pfizer. EB has also received a research grant from Gilead for fatty liver research.
VR: received consulting fees from Novo Nordisk, Sagimet, Madrigal, Enyo, Poxel, Northsea, Intercept and ProSciento, and research grants (to institution) from Gilead and Intercept.
MER: consults for Boehringer Ingelheim, CytoDyn, GSK, Novo Nordisk, HistoIndex, Intercept, Madrigal, NGM Bio and Sonic Incytes.
MR: reports grants from Boehringer Ingelheim and Novo Nordisk, and has received fees for consulting or participation in advisory boards for Boehringer Ingelheim, Echosens, Eli Lilly and Novo Nordisk. MR also reports honoraria as a speaker for AstraZeneca, Boehringer Ingelheim, Novo Nordisk and Madrigal.
AJS: consults for and advises Avant Santé and AstraZeneca. AJS also consults for and has received grants from Akero, BMS, Intercept, Eli Lilly, Madrigal and Novo Nordisk. AJS consults for and owns stock in Rivus, and also consults for AGED Diagnostics, Albireo, Alnylam, Altimmune, Boehringer Ingelheim, 89Bio, Echosens, Genentech, Gilead, GSK, HistoIndex, Mallinckrodt, Merck, NGM Bio, Novartis, PathAI, Pfizer, Poxel, Regeneron, Salix, Siemens, Surrozen, Takeda, Terns and Zydus. AJS owns stock in Durect, Exalenz, Genfit, Indalo, Inversago and Tiziana, and has received royalties from Elsevier and Wolters Kluwer.
KAE, IK, LHØ, DV and JZ: employees and stockholders of Novo Nordisk A/S.

Introduction

Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) is the most prevalent hepatic disorder worldwide. While histology remains the gold standard, a shift is evident in emerging studies favoring Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) over biopsy as a reliable alternative for steatosis assessment. Similarly, Controlled Attenuation Parameter (CAP) enables the noninvasive assessment of liver steatosis.

Aims & Methods

To assess the accuracy of CAP for MASLD diagnosis as defined by MRI-PDFF. We performed a cross-sectional, diagnostic accuracy study with prospectively collected data. We included consecutive adult participants with type 2 diabetes (T2D) and increased body mass index (BMI ≥25 kg/m²). We used receiver operating characteristic (ROC) curve analyses to assess the accuracy of CAP for diagnosing MASLD (MRI-PDFF ≥5%), and hepatic fat content (HFC) ≥10%. For each ROC analysis, we calculated the area under the ROC (AUROC) alongside 95% Confidence Intervals (CIs), and cutoffs for ruling out (sensitivity >90%) and ruling in (specificity >90%) the target condition. For each cutoff, we calculated the negative (NPV) and positive predictive values (PPV), as well as negative (LRn) and positive (LRp) likelihood ratios with their 95% CIs.

Results

We included 113 participants (58.4% males, mean age 59.6 years). Most participants (95.6%) had a BMI ≥30 kg/m². CAP measurements were performed with the M probe in 36.3% of the participants, and the remaining (63.7%) were scanned with the XL probe. MRI-PDFF values ranged from 1.9% to 37.8% covering the whole spectrum of steatosis. The prevalence of MASLD was 72.6%. The AUROC of CAP for MASLD diagnosis was 0.82 (0.74 to 0.89). The threshold for ruling out MASLD was 249 dB/m yielding a sensitivity (Sens) of 90.2% (81.7 to 95.7), specificity (Sp) 35.5% (19.2 to 54.6), LRp 1.40 (1.07 to 1.83), LRn 0.27 (0.12 to 0.62), PPV 78.7% (73.8 to 82.9) and NPV 57.9% (37.9 to 75.6). Similarly, the threshold for ruling in MASLD was 328 dB/m yielding a Sens, Sp, LRp, LRn, PPV and NPV of 47.6% (36.4 to 58.9), 90.3% (74.2 to 98.0), 4.91 (1.64 to 14.75) and 0.58 (0.46 to 0.74), 92.9% (81.2 to 97.5) and 39.4% (34.0 to 45.2), respectively. The AUROC of CAP for detecting HFC ≥10% was 0.81 (0.73 to 0.88). CAP thresholds for ruling out/in HFC ≥10% were 271 dB/m and 345 dB/m respectively. CAP measurements with IQR < 30 dB/ did not improve the accuracy of CAP for MASLD diagnosis

Conclusion

CAP has acceptable diagnostic accuracy in identifying patients with MRI-PDFF defined MASLD. Thresholds below 249 and 271 dB/m can be used to exclude MALSD and HFC ≥10% with adequate sensitivity. Similarly, CAP values over 328 and 345 dB/m can rule in MASLD and HFC ≥10% respectively.

Disclosure

This study was supported by the Hellenic Association for the Study and Education of Diabetes Mellitus

Introduction

Clostridioides difficile infection (CDI) is among of the most common causes of nosocomial diarrhea with high morbidity and mortality. Recurrent and refractory disease courses in particular represent a special challenge in the management of these patients. The identification of patients at risk for recurrent courses could improve management, e.g. through the use of new and effective therapies in patients with CDI.

Aims & Methods

The aim of this study was to investigate the relationship between the presence of different comorbidities and the course of CDI.
In a retrospective, monocentric cohort study of a tertiary centre over a period of 10 years, patients with CDI-related hospitalizations were examined. The study included 336 patients with available information on comorbidities (diverticulosis, biliary diseases (cholecysto-, docholithiasis, cholecystitis, cholangitis or cholangiectasis) inflammatory bowel diseases (IBD), liver cirrhosis and malignancies) and the diagnosis of the recurrent CDI (rCDI) vs. non-recurrent course of CDI (nrCDI). Patients on dialysis or immunosuppressed patients were also considered as comorbid.

Results

Among 336 patients included in the study, 227 (67.6%) presented with at least one comorbidity. The most common were malignancy (30.4%), biliary diseases (19.4%), diverticulosis (15.8%), liver cirrhosis (14.3%), and inflammatory bowel disease (IBD, 8.9%). rCDI occurred more frequently in patients with diverticulosis and biliary disease. Diverticulosis was present in 24.4% of rCDI cases vs. 12.6% in nrCDI cases (OR 2.24, 95% CI 1.22–4.17). Biliary diseases were observed in 26.7% of rCDI vs. 16.7% of nrCDI patients (OR 1.82, 95% CI 1.01–3.26). No significant associations with rCDI were found for IBD (OR 0.66, 95% CI 0.27–1.65), malignancy (OR 1.13, 95% CI 0.67–1.88), or liver cirrhosis (OR 0.79, 95% CI 0.38–1.61).

Conclusion

These findings suggest diverticulosis and biliary disease may be independent risk factors for rCDI, whereas other common comorbidities are not significantly associated with recurrence. Structured assessment of risk conditions may help to select patients for tailored management to prevent rCDI disease course.

Introduction

With about 40% of adults infected with Helicobacter pylori (H. pylori), China has the highest number of gastric cancer (GC) cases worldwide.¹ Household transmission is the primary route for H. pylori infection,² and family-based testing and treatment has been proposed to mitigate GC cancer risk and prevent transmission.^1,3,4 A household-based transmission model for H. pylori would enhance understanding of H. pylori dynamics and inform intervention strategies. However, few models⁵ have been developed for H. pylori, and none incorporates household transmission.

Aims & Methods

We developed an agent-based household transmission model for H. pylori in China to study transmission patterns from 1990 to 2021. Building on our previous modeling framework,⁶ the model includes demographic and transmission components. The demographic simulation captures births, deaths, marriages, and mobility among youth, couples, and the elderly. Mobility parameters were calibrated using joint distributions of household size and generation from Chinese censuses of 1990, 2000, 2010, and 2020, allowing realistic household dynamics in China. In the transmission simulation, household and community transmissions were modeled using a susceptible-infected structure, applying density-dependent transmission within households and frequency-dependent transmission in the community. Contact rates, defined as the number of contacts adequate for transmission by an individual per year, were allowed to vary over time, and were dependent on the susceptible individual’s age. Contact rate variation was modeled by adjusting base rates with age- and year-specific multipliers, each following a continuously decreasing function. Simulations began in 1900, with the first 90 years as a burn-in period. Transmission parameters were calibrated and validated using data from our meta-analyses and a large national family-based survey from China in 2021⁷.

Results

The model aligned well with calibration targets. Key parameters and calibration results are summarized in the Table. Consistent with observed data, larger households had higher infection rates than smaller households. Three-generation households were more likely to have infected members than one- or two-generation households. Model calibration showed best fit when the within-household contact rate (0.2) was higher than the community rate (0.1), and when most infections occurred before age 20. Validation confirmed model accuracy: children’s infection probabilities were 31% with both parents infected, 21% with one infected parent, and 9% with neither. Our model found that family clustering became more pronounced in recent years with lower prevalence compared to earlier periods with higher prevalence.

Table. Calibration and validation results for the transmission model

Conclusion

We developed a novel agent-based model simulating community and household transmission of H. pylori. Our results confirm that household transmission is the primary infection route, and that childhood is the predominant period of acquisition. Notably, family clustering becomes more prominent in low-prevalence contexts. This model provides a valuable tool for evaluating various control strategies and offers insights difficult to obtain in real-world data. Future extensions could incorporate antibiotic resistance dynamics and adapt the model to other country contexts.

References

1. Ding, S.-Z. et al. Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition). Gut 71, 238–253 (2022).
2. Malfertheiner, P. et al. Helicobacter pylori infection. Nat. Rev. Dis. Primer 9, 1–24 (2023).
3. Chey, W. D. et al. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Off. J. Am. Coll. Gastroenterol. ACG 119, 1730 (2024).
4. Shah, S. C., Wang, A. Y., Wallace, M. B. & Hwang, J. H. AGA Clinical Practice Update on Screening and Surveillance in Individuals at Increased Risk for Gastric Cancer in the United States: Expert Review. Gastroenterology 168, 405-416.e1 (2025).
5. Rupnow, M. F. T., Shachter, R. D., Owens, D. K. & Parsonnet, J. A Dynamic Transmission Model for Predicting Trends in Helicobacter pylori and Associated Diseases in the United States. Emerg. Infect. Dis. 6, 228–237 (2000).
6. Blok, D. J. et al. The long-term impact of the Leprosy Post-Exposure Prophylaxis (LPEP) program on leprosy incidence: A modelling study. PLoS Negl. Trop. Dis. 15, e0009279 (2021).
7. Zhou, X.-Z. et al. Large-scale, national, family-based epidemiological study on Helicobacter pylori infection in China: the time to change practice for related disease prevention. Gut 72, 855–869 (2023).B1