Introduction

According to recent studies, the prevalence rate of H. pylori infection in Russia is over 30%, but a decreasing trend has recently been observed. Comprehensive multicenter evaluation of effectiveness of different eradication treatments in Russia has not yet been performed. One of the most efficient tools of such analysis is the on-going European Registry on H. pylori Management (Hp-EuReg), an international, prospective, multicenter, observational study, which begun in 2013.

Aims & Methods

The objective of our study was to evaluate the effectiveness of first-line empirical eradication therapy in Russia between 2013-2022 according to the data of Hp-EuReg. The treatment effectiveness was analysed by per-protocol (PP), and modified intention-to-treat (mITT), also stratifying by PPI dose (low dose - 4.5 to 27 mg omeprazole equivalent, twice daily; standard dose - 32 to 40 mg omeprazole equivalent, twice daily; high dose - 54 to 128 mg omeprazole equivalent, twice daily) and duration of treatment (7, 10 or 14 days).

Results

Overall, 8,354 patients from 14 cities in Russia who had received a first-line empirical eradication therapy between 2013 and 2022, were included. Invasive (i.e. endoscopic) methods (rapid urease test, histology/cytology) for the H. pylori primary evaluation were mostly used in almost all cities. The highest rate of ¹³C-urea breath test was observed in Rostov-on-Don (89% of cases), Saint-Petersburg (37%), Omsk (25%), Perm (25%), and Moscow (23%). The most frequently used first-line treatments were: triple (PPI, amoxicillin, clarithromycin) and triple plus bismuth (PPI, amoxicillin, clarithromycin, bismuth) therapies, accounting for more than 60% of prescriptions in almost all cities. Most cities prescribed 14-day length therapies; whereas standard PPI doses were most frequently used in Chelyabinsk (94%), Smolensk (84%), Saint-Petersburg (68%), Moscow (67%), Khabarovsk (66%) and Rostov-on-Don (54%), low PPI doses prevailed in Krasnoyarsk (80%), Izhevsk (70%), Novosibirsk (65%), Omsk (60%), and Kazan (52%). Quadruple therapy with PPI, amoxicillin, clarithromycin and bismuth achieved optimal (>90%) mIIT effectiveness in Saint-Petersburg, Perm, Chelyabinsk, and Khabarovsk, where it was more frequently used than in the remaining cities. Effectiveness of triple therapy (PPI, amoxicillin, clarithromycin) varied from 62% (Novosibirsk) to 99% (Omsk), achieving over 85% across all cities. However, high eradication rates with triple therapy prescriptions were observed in the cities with a small number of patients or in those cases where histology were the unique tests used for eradication control, possibly giving false negative results. Classic bismuth quadruple therapy (PPI, tetracycline, metronidazole, bismuth) provided optimal (>90%) mITT effectiveness in Moscow and Saint-Petersburg, where it was predominately used as compared to other cities (table 1).

Table.1 Effectiveness by modified intention-to-treat of most common first-line empirical therapies in 14 cities of Russia in 2013-2022

Eradication therapy	Moscow	St. Petersburg	Kazan	Perm	Kovrov	Chelyabinsk	Khabarovsk	Rostov-On-Don	Smolensk	Cheboksary	Omsk	Krasnoyarsk	Novosibirsk	Izhevsk	Overall
Triple therapy (PPI+A+C)	83.4%	87%	77.2%	89.2%	76.1%	96.3%	72.6%	88.3%	78%	94%	99.1%	81.7%	62%	100%	83.1%
Quadruple therapy (PPI+M+Tc+ bismuth)	92.1%	91.4%	100%	100%	80%	100%	100%	-	100%	100%	100%	-	-	-	92.9%
Quadruple therapy (PPI+A+C+ bismuth)	88.3%	93.1%	86.4%	95.2%	87.3%	100%	92.4%	100%	86.7%	96.2%	100%	-	71.4%	91.2%	92.7%

PPI: proton pump inhibitor; A: amoxicillin; C: clarithromycin; M: metronidazole; B: bismuth salts; Tc: tetracycline

Conclusion

To date, in Russia, bismuth quadruple therapies either with classical metronidazole-tetracycline-bismuth or amoxicillin-clarithromycin-bismuth achieve optimal (> 90%) results, providing significantly better rates when prescribed for 14 days

Introduction

Altered gut microbiome composition has been implicated in the pathogenesis of inflammatory bowel disease (IBD). However, detailed characterization of microbial diversity differences between IBD subtypes remains incomplete. This study aimed to evaluate gut microbiome alpha diversity in patients with Crohn's disease (CD) and ulcerative colitis (UC) compared to healthy controls using long-read 16S rRNA sequencing technology.

Aims & Methods

Fecal samples were collected from 17 patients with CD, 20 patients with UC, and 192 healthy controls without IBD. DNA was extracted using an SKYAmp stool DNA kit (SkyGen, Russia). Long-read nanopore sequencing of 16S rRNA amplicons was conducted using a MinIon™ sequencer. Taxonomic assignment was performed with EMu software by aligning FASTQ reads to the NCBI 16S database [1]. Alpha-diversity was evaluated at the species level using Chao1 and Shannon indices. Statistical comparisons between groups were conducted using Welch two-sample t-tests with Holm adjustment in R environment and the RStudio software (version 4.4.1).

Results

	Without IBD	CD	UC
Shannon index	3.452 (3.410 - 3.494)	3.165 (2.970 - 3.360)	3.270 (3.016 - 3.524)
Chao1 index	85.750 (84.046 - 87.454)	67.529 (61.087 - 73.972)	74.650 (64.729 - 84.571)

The Shannon diversity index was significantly lower in the CD group compared to the control group (p=0.01412), while no significant difference was observed between UC and control groups (p=0.15461). Chao1 richness index values were significantly reduced in both CD and UC patient groups compared to controls (p=0.00003 and p=0.03195, respectively), indicating reduced species richness in both IBD conditions.

Conclusion

This study demonstrates that both IBD subtypes exhibit reduced microbial richness as measured by the Chao1 index, while significant reduction in Shannon diversity was observed only in CD patients. These findings suggest differential impacts of CD and UC on gut microbiome composition, with CD potentially having more profound effects on overall microbial diversity. Long-read 16S rRNA sequencing provides valuable insights into the microbial signatures associated with different IBD phenotypes, which may contribute to improved diagnostics and personalized treatment approaches.

References

1. Curry KD, et al. Emu: Species-level microbial community profiling of full-length 16S rRNA Oxford Nanopore sequencing data. Nature Methods. 2022;19(7):845-853

Introduction

HCC is well known complication of liver cirrhosis. The current standard of care for patients with cirrhosis involves systematic 6 monthly screening with ultrasound and serum alpha-fetoprotein testing. (1) The Aberdeen Hepatoma surveillance clinic has been instituted since 2005 and currently 707 patients under screening program. It is a one-stop nurse led clinic wherein the ultrasound scan, blood testing and clinical review is done in a single visit, with sequential visits planned every 6 months. ​

Aims & Methods

In this study we aimed to identify outcome of HCC detected in hepatoma clinic compared to those identified symptomatically. Data collected retrospectively of patients referred to HCC MDT at Aberdeen Royal infirmary over period of 5 years. Diagnosis of HCC was made based on liver ultrasound and serum AFP as per guidelines

Results

130 patients were identified with HCC through both pathways. 17 patients were detected as part of the surveillance programme and the rest were directly referred to the HPB MDT through the symptomatic pathway. The predominant subjects were males 102 (78.4%) and the cause of liver cirrhosis was as follows: MASLD 39%, ARLD 29%, Chronic HCV 11%, HBV 4%, Haemochromatosis 3%, PBC 2%, autoimmune hepatitis and PSC 1%. The mean age of patients detected in the surveillance group was 65 years ± 6.14 SD as opposed to those in the symptomatic group 71 years ± 9.99 SD. AFP was normal in 50% of surveillance group. The BCLC staging in the surveillance group was stage 0-A (20%), stage B 45%, In the symptomatic group patients were in stage 0-A 7%, Stage B 22%, and stage C, D 55% respectively.
Curative options including liver transplant and resection was possible in 20 % of surveillance patients as opposed to 7% in symptomatic patients. Palliative options like RFA, TACE and Sorafenib was offered in 60% of surveillance patients and 42% of symptomatic patients. In 20 % of surveillance patients no treatment could be offered as opposed to 55% symptomatic patients.

Conclusion

The mean age of the patients detected in the surveillance clinic was 5 years less than the symptomatic group suggesting that the programme was picking patients early. More curative and palliative procedures could be offered to this subgroup for this reason. The BCLC staging confirmed that most patients in the surveillance programme were in the early stages as opposed to the symptomatic group. Despite having an entrenched surveillance programme most patients were presenting symptomatically, suggesting that more efforts are needed to identify patients with cirrhosis who are at an added risk for developing HCC.

References

1. European Association for the Study of the Liver. EASL Policy Statement on liver cancer screening. Accessed 31 May 2022. Available from: https://easl.eu/publication/easl-policy-statement-on-liver-cancerscreening/.

Introduction

Fecal calprotectin (FC) is a key non-invasive biomarker used to monitor inflammatory bowel disease (IBD). Despite its clear clinical value, patient adherence to the test remains suboptimal, mainly due to reluctance related to stool collection. The objective of the ACCALMI study was to compare the acceptability of a new stool collection device, similar to the one used for fecal immunochemical tests (FIT), with a standard stool container, and to evaluate its impact on patient compliance.

Aims & Methods

In this prospective, single-center study, 156 patients with an established diagnosis of IBD and who had been prescribed an FC test as part of their routine care, were randomly assigned to either the standard container group or the alternative device group (Procise Stool Collection Device™), which includes a collection tube with a thin spiral-shaped probe facilitating stool collection. Acceptability was assessed using a 4-category ordinal scale (from "poor" to "very good") and a visual analog scale (VAS, from 0 to 10). Analyses were conducted in both per-protocol and intention-to-treat (ITT) populations, with missing data handled using the maximum bias method. Factors associated with improved FC acceptability, and compliance with FC testing, were analyzed.

Results

The alternative collection device significantly improved acceptability as measured by the ordinal scale (odds ratio [OR] 2.69; p < 0.001). In the alternative group, acceptability ratings were significantly higher with only 1.4% versus 7.0% rating it as ‘poor’, 12.5% versus 46.6% as ‘average’, 66.7% versus 40.8% as ‘good’, and 19.4% versus 5.6% as ‘very good’. Measured using the VAS, the average acceptability was 7.9/10 in the group using the alternative device compared to 6.1/10 in the standard group, with a significant difference of 30.4% (95% CI [19.7 - 44.7%], p < 0.001), although it did not reach the threshold of 30% that was set a priori. The ITT analysis led to the same conclusions. Among the patients who had already undergone FC testing and were randomized to the "alternative device" group, 55% indicated a preference for the alternative device, compared to 7.2% for the conventional device, while 37.7% found them similar. Embarrassment and discomfort associated with the standard container were alleviated by the alternative device. A long home-to-hospital distance (> 50 km) and the use of the alternative device were the only factors associated with better acceptability in the multivariate analysis. Compliance was similar between both groups and remarkably high (92%).

Conclusion

The ACCALMI study demonstrated that the alternative stool collection device, similar to the one used in FIT for colorectal cancer screening, is more accepted by IBD patients than the standard container, thus improving the acceptability of FC testing. These findings support the integration of patient-centered innovations in diagnostic and follow-up testing to improve the monitoring of IBD.

Disclosure

Acknowledgments: Collaboration with Biosynex®.

Introduction

Gastric cancer remains a major health challenge globally, with Helicobacter pylori (H. pylori) infection being a well-known risk factor. Despite significant advances in understanding the pathological mechanisms of gastric cancer, the specific interactions between H. pylori and the host immune system within the tumor microenvironment are not fully elucidated. This study leverages cutting-edge spatial transcriptomic technologies to explore these interactions in gastric cancer samples.

Aims & Methods

This research aims to elucidate the mechanisms through which H. pylori contributes to immune evasion in the gastric cancer microenvironment. We utilized spatial transcriptomics on 71 gastric cancer samples, supplemented by single-cell transcriptomics on 10 of these samples to achieve a high-resolution view of cellular interactions. Advanced analytical techniques, including cell interaction networks, neighborhood analysis, and deconvolution mapping, were employed to dissect the complex interplay between tumor cells, immune cells, and H. pylori.

Results

Our results reveal a sophisticated mechanism by which H. pylori induces the recruitment and activation of cancer-associated fibroblasts (CAFs) and regulatory T cells (Tregs), facilitating an immunosuppressive tumor microenvironment. Spatial transcriptomics highlighted significant alterations in gene expression patterns conducive to immune evasion, primarily mediated by the interaction between H. pylori, CAFs, and Tregs. The integration of single-cell and spatial data provided a detailed map of the immune landscape, revealing key nodes and pathways involved in this process.

Conclusion

The findings of this study provide compelling evidence of H. pylori’s role in shaping the immune landscape of gastric cancer towards immunosuppression through the modulation of CAFs and Tregs. These insights underscore the potential benefits of immunotherapeutic strategies tailored for H. pylori-positive gastric cancer patients. Future therapeutic interventions could focus on targeting these specific interactions to enhance the efficacy of cancer immunotherapy in this cohort.

Disclosure

Introduction

Since 2010 (1), little data has been available in France on the management of severe acute alcoholic hepatitis (SAH). In order to obtain a current "mapping" of the management of severe HAS in France, a practice survey was conducted from 04/2022 to 07/2023.

Aims & Methods

A Google questionnaire pre-established by a working group was sent to all the hepatogastroenterology departments of general hospitals (nUH), the hepatology departments of university hospitals (UH). The results are expressed as means ± SD. Data analysed: demographics, type of practice (university hospital, general hospital), predominant speciality, experience, number of AA treated per centre with corticosteroids (C) or N-acetylcysteine corticosteroids (NAC). Existence of an AA treatment protocol. Systematic use of transjugular liver biopsy (LB), on-site LB, time taken to obtain results. Treatment: use of C alone or C-NAC. Screening for bacterial infections, use of antibiotic therapy (ATB) in the event of infection, time taken to start treatment for AA. Whether or not to use C in antigen-positive HBs patients (with or without pre-emptive treatment). Interruption of C in the event of an intermediate Lille score at D7. Indication for transfer to a liver transplant centre.

Results

465 respondents (R): 40 years (12.5); 50% M, 50% F, UH 53.3%, nUH 46.7%, hepatologists 57%, gastroenterologists 39%, juniors 21%. Number of AA treated with CS or CS NAC 25 (0 to 300); the number of AA treated in UH was higher than in non UH: 34 (29), nUH 15.4 (13.4), p < 0.001. Treatment protocol for AA, 62% (University Hospital) vs 42% (Hospital), p < 0.001. LB systematically performed: 98% AA vs 50% other, p < 0.001. Time taken to obtain LB (days): 3.4 (UH) vs 4.9 (nUH), p < 0.001. Nutritional status was assessed by 98% of patients. A systematic chest CT scan was routinely requested by 34% of patients in the event of suspected pulmonary infection (UH versus nUH ns); 83% of patients waited 4 days (2-6) before starting treatment in the event of documented infection. Treatment: C alone 70% of patients (UH vs nUH ns), NAC use: UH 40% vs nUH 47.3% (ns). Treatment protocol for alcohol withdrawal syndrome: 86.3% nUH vs 76.3% UH (p < 0.01). CS stopped in the event of an intermediate Lille score at D7: 80% nUH vs 77% UH; ns. 69% of R's were responsible for initiating treatment. 68.2% of R were responsible for initiating treatment; 64.7% in UH vs 72.3% (NS); 80.6% senior doctors vs 20.4% junior doctors (p<0.001). 62% of R used pre-emptive treatment before CS in the case of a positive HBs antigen; 59.4% in UH vs 65% in nUH (p=0.004) and 76% used upper gastrointestinal endoscopy if there had been none previously, 77% in UH vs 75% nUH (p=0.782).

Conclusion

The results of this study of national practice carried out in a large sample of doctors practising in or outside university hospitals show a disparity in the use of LB in cases of suspected severe AA, since 50% of R outside university hospitals do not use LB, mainly because of the absence of local possibilities. Dual C-NAC therapy is used fairly frequently. There is a disparity between university hospitals and general hospitals in the management of alcohol withdrawal syndrome and pre-emptive treatment in cases of positive HBs antigen. This study provides an update on the management of severe AA in France.

References

E.Nguyen-Khac et al J Hepatol 2010 (abstract)

Introduction

The brain-gut axis plays a crucial role in the regulation of gastrointestinal (GI) function, with the activity of the autonomic nervous system (ANS) being significantly important. Increased stress, correlated with socioeconomic, behavioral, dietary, and environmental factors, may lead to an overactive sympathetic nervous system response. The aim of this study was to evaluate the correlation between stress and autonomic nervous system responses in gastrointestinal patients.

Aims & Methods

The study comprised 136 GI patients, divided into three groups: the Dyspepsia Group (DG) with 39 patients, a mean age of 37.8 ±11.2 years; the IBS Group (IBS) with 41 patients, a mean age of 45±15 years; and the Celiac Group (CG) with 53 patients, a mean age of 38.2±14 years. ANS activity was assessed using parameters from Heart Rate Variability (HRV) analysis, including time domain, frequency domain, and nonlinear analysis. The severity of stress was assessed using stress indices calculated based on hemodynamic parameters and indicators from linear and nonlinear HRV analysis with the HRV Kubios Premium software.

Results

Patients in the IBS Group exhibited the highest stress indicators and sympathetic ANS activity parameters compared to those in the DG and CG groups (SNS index [stress] p=0.038, SNS index AVG p=0.038). Furthermore, the IBS Group had higher stress indices compared to the DG Group (Stress Index 14.0 vs 9.0; p=0.024). Positive correlations were found between the Stress Index, SNS index (stress), and average heart rate (R=0.525; p=0.0001), as well as with sympathetic ANS activity indices. Negative correlations were observed with indicators of parasympathetic nervous system activity across all investigated groups (R=0.433; p=0.001). A high level of stress, indicated by a Stress Index value above 12, was found in 18% of patients with CD, 38% with IBS, and 28% with DG.

Conclusion

Approximately 27% of GI patients experienced significant levels of stress. The stress indicators positively correlated with sympathetic ANS activation and/either impaired function of the parasympathetic system. Assessing the severity of stress will enable targeted therapy to improve the dysfunctions of the brain-gut axis.