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Introduction

Dysbiosis of the gut microbiota is involved in the etiopathogenesis of primary biliary cholangitis (PBC). Escherichia coli infection plays a key role in the breakdown of self-immune tolerance, leading to the production of anti-mitochondrial antibodies (AMA). However, the role of intestinal E. coli in PBC remains unclear. Urinary tract infection (UTI) mainly caused by E. coli is a significant risk factor for the onset of PBC. Therefore, we hypothesized that there was a specific strain of uropathogenic E. coli present in the intestine of PBC participating in the pathogenesis of PBC.

Aims & Methods

The aim of the study was to investigate the role of intestinal E. coli in the pathogenesis of PBC. We isolated E. coli strains from the feces of sex- and age- matched PBC patients (n=31) and healthy controls (n=30). We screened the potential E. coli strain depending on the fimbrial gene distribution patterns. Both C57BL/6J and dnTGFβRII mice were gavaged with the screened E. coli strain, E. coli-K12 (K12) and PBS respectively. Liver biopsies from PBC patients and control populations were collected to confirm the distribution of the screened E. coli.

Results

1. We isolated 93 and 90 strains of E. coli from the feces of PBC and healthy controls, respectively. By analyzing the distribution patterns of the fimbrial genes, we identified a strain of E. coli called Ex colonizing in the intestines of PBC specifically, which also caused UTI in patients.
2. We detected a high titre of AMA in the serum of C57BL/6J mice colonized by Ex rather than K12, a control E. coli strain. Furthermore, Ex-infected mice presented severe intestinal barrier destruction compared with K12-infected mice. Ex translocated to the mesenteric lymph nodes (MLN) and liver in Ex-infected mice by fluorescence in situ hybridization, while K12 or PBS-gavaged mice did not. Flow cytometry analysis revealed a significant increase in the proportion of CD11C⁺MHCII⁺CD103⁺ inflammatory dendritic cells (DCs) in the MLN of Ex-infected mice.
3. We gavaged Ex to 4-week-old dnTGFβRII mice that had not yet developed cholangitis. It revealed that Ex-gavage induced earlier production of AMA and significantly enhanced cholangitis compared to K12 and PBS-gavage. Flow cytometry analysis revealed that besides a significant increase in inflammatory DCs in MLN, the proportion of CD8⁺T cells and CD20⁺ B cells increased in Ex-infected dnTGFβRII mice.
4. Using 16S rRNA gene sequencing of liver biopsies, the abundance of bacteria and E. coli in PBC livers was significantly increased. Interestingly, we detected E. coli around the bile ducts in PBC liver biopsies by means of specific probes, while the autoimmune hepatitis and non-alcoholic fatty liver disease livers were not.

Conclusion

Our results suggest that an uropathogenic Escherichia coli strain may be the critical causative pathogen for PBC by disrupting the intestinal barrier and translocating to the liver.

References

[1] Tang R, Wei Y, Li Y, et al. Gut microbial profile is altered in primary biliary cholangitis and partially restored after UDCA therapy. Gut. 2018. 67(3): 534-541.
[2] Lleo A, Leung P, Hirschfield GM, Gershwin EM. The Pathogenesis of Primary Biliary Cholangitis: A Comprehensive Review. Semin Liver Dis. 2020. 40(1): 34-48.
[3] Yang Y, Choi J, Chen Y, et al. E. coli and the etiology of human PBC: Antimitochondrial antibodies and spreading determinants. Hepatology. 2022. 75(2): 266-279.

AN UROPATHOGENIC ESCHERICHIA COLI STRAIN INDUCED CHOLANGITIS IN THE PROGRESSION OF PRIMARY BILIARY CHOLANGITIS

Hongyu Chu 1, Yuhang Liu 1, Jianming Yang 2, Rongrong Zheng 1, Xiaoyi Wang 1, Qiang Tang 2, Xue Zhang 1, Nian Chen 1, Hao Jia 1, Jiangpeng Liu 1, BANGMAO WANG 3, Quan Wang 2, Yanni Li 1, Lu Zhou 1

1 Tianjin Medical University General Hospital, Tianjin, China

2 Tianjin Medical University, Tianjin, China

3 TianJin Medical University General Hospital, Tianjin, China

Conference

UEG Week Copenhagen 2023

Topics

Hepatobiliary

Submission format

Abstract

Session

Biliary and cholostatic disease (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

UEG Standards and Guidelines

Clinical Practice Guideline

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Summary

Non-invasive tests are increasingly being used to improve the diagnosis and prognostication of chronic liver diseases across aetiologies. Herein, we provide the latest update to the EASL Clinical Practice Guidelines on the use of non-invasive tests for the evaluation of liver disease severity and prognosis, focusing on the topics for which relevant evidence has been published in the last 5 years.

EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 update

Publisher

European Association for the Study of the Liver

Guideline

Clinical Practice Guideline

Topics

Hepatobiliary

Citation

Journal of Hepatology, Volume 75, Issue 3, 659 - 689

Published

2021

UEG Presentation

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Panel discussion: Liver and pregnancy - Beware of dangerous liaisons

Event

UEG Postgraduate Teaching Programme Berlin 2025

Topics

Hepatobiliary Paediatrics

Session

Liver and pregnancy: Beware of dangerous liaisons

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

UEG Standards and Guidelines

Clinical Practice Guideline

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Summary

Acute kidney disease (AKD) - which includes acute kidney injury (AKI) – and chronic kidney disease (CKD) are highly prevalent among hospitalized patients, including those in nephrology and medicine wards, surgical wards, and intensive care units (ICU), and they have important metabolic and nutritional consequences.

Moreover, in case kidney replacement therapy (KRT) is started, whatever is the modality used, the possible impact on nutritional profiles, substrate balance, and nutritional treatment processes cannot be neglected.

The present guideline is aimed at providing evidence-based recommendations for clinical nutrition in hospitalized patients with AKD and CKD. Due to the significant heterogeneity of this patient population as well as the paucity of high-quality evidence data, the present guideline is to be intended as a basic framework of both evidence and - in most cases - expert opinions, aggregated in a structured consensus process, in order to update the two previous ESPEN Guidelines on Enteral (2006) and Parenteral (2009) Nutrition in Adult Renal Failure. Nutritional care for patients with stable CKD (i.e., controlled protein content diets/low protein diets with or without amino acid/ketoanalogue integration in outpatients up to CKD stages four and five), nutrition in kidney transplantation, and pediatric kidney disease will not be addressed in the present guideline.

Keywords: Acute kidney disease, Acute kidney injury, Clinical nutrition, Kidney replacement therapy, Hospitalized patients, Intensive care unit, Malnutrition, Muscle wasting

ESPEN guideline on clinical nutrition in hospitalized patients with acute or chronic kidney disease

Enrico Fiaccadori

Publisher

The European Society for Clinical Nutrition and Metabolism

Guideline

Clinical Practice Guideline

Topics

Small Intestine & Nutrition

Citation

Clinical Nutrition, Volume 40, Issue 4, 1644 - 1668

Published

2021

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Introduction

Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction with alcohol-related steatotic liver disease (MetALD) are two separate entities within the spectrum of steatotic liver disease (SLD).

Aims & Methods

This meta-analysis aims to compare the risks of hepatic and extrahepatic outcomes between MASLD and MetALD. We systematically searched for observational cohort studies published up to March 1, 2025, comparing clinical outcomes between individuals with MASLD and MetALD. The primary outcome was liver-related events, while secondary outcomes included hepatocellular carcinoma (HCC), liver-related mortality, cardiovascular events, extrahepatic cancers, and all-cause mortality. We used random-effect models to calculate pooled hazard ratios (HRs) with 95% confidence intervals (95% CI).

Results

Twenty-four studies involving 11,396,962 individuals were analyzed (9,622,716 with MASLD and 1,774,246 with MetALD). Individuals with MetALD had significantly higher risks of liver-related events (HR 1.62, 95% CI 1.16-2.25, p=0.02) and HCC (HR 1.33, 95%CI 1.00-1.77, p=0.04) than those with MASLD. The risk of extrahepatic cancers was also increased in MetALD (HR 1.03, 95% CI 1.01-1.06, p<0.001), while the rates of cardiovascular events (HR 0.96, 95% CI 0.85-1.09, p=0.48), extrahepatic cancer-related mortality (HR 1.44, 95% CI 0.97-2.15, p=0.07), and all-cause mortality (HR 1.08, 95% CI 0.97-1.19, p=0.14) did not differ between these two conditions.

Conclusion

MetALD confers a higher risk of liver-related outcomes, HCC, and extrahepatic cancers than MASLD, while all-cause mortality and cardiovascular risk are similar between the two conditions. These findings emphasize the need for distinct clinical strategies for these related yet different entities within the SLD spectrum and highlight the importance of conducting pharmacological clinical trials in this context.

Disclosure

Nothing to disclose

COMPARATIVE EFFECTS OF METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE AND METABOLIC AND ALCOHOL-ASSOCIATED STEATOTIC LIVER DISEASE (METALD) ON RISK OF HEPATIC AND EXTRA-HEPATIC OUTCOMES: A META-ANALYSIS

Ciro Celsa 1, Grazia Pennisi 2, Adele Tulone 1, Giacinta Ciancimino 1, Marco Vaccaro 1, Fabiana Pecorella 1, Gabriele Di Maria 1, Marco Enea 1, Calogero Camma 1, Salvatore Petta 1

1 University of Palermo, Palermo, Italy

2 Policlinico Paolo Giaccone, Palermo, Italy

Conference

UEG Week Berlin 2025

Topics

Hepatobiliary

Submission format

Abstract

Session

MASLD: Clinical aspects, experimental and pathology (Posters)

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

UEG Standards and Guidelines

Clinical Practice Guideline

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Summary

This guideline will inform physicians, nurses, dieticians, pharmacists, caregivers and other home parenteral nutrition (HPN) providers, as well as healthcare administrators and policy makers, about appropriate and safe HPN provision. This guideline will also inform patients requiring HPN. The guideline is based on previous published guidelines and provides an update of current evidence and expert opinion; it consists of 71 recommendations that address the indications for HPN, central venous access device (CVAD) and infusion pump, infusion line and CVAD site care, nutritional admixtures, program monitoring and management. Meta-analyses, systematic reviews and single clinical trials based on clinical questions were searched according to the PICO format. The evidence was evaluated and used to develop clinical recommendations implementing Scottish Intercollegiate Guidelines Network methodology. The guideline was commissioned and financially supported by ESPEN and members of the guideline group were selected by ESPEN.

Keywords: Central venous access device, Intestinal failure, Multidisciplinary team, Parenteral nutrition admixture, Patient training

ESPEN guideline on home parenteral nutrition

Loris Pironi

Publisher

The European Society for Clinical Nutrition and Metabolism

Guideline

Clinical Practice Guideline

Topics

Primary Care Small Intestine & Nutrition

Citation

Clinical Nutrition, Volume 39, Issue 6, 1645 - 1666

Published

2020

UEG Standards and Guidelines

Clinical Practice Guideline

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Abstract

Background

Variation exists in practice pertaining to bowel preparation before minimally invasive colorectal surgery. A survey of EAES members prioritized this topic to be addressed by a clinical practice guideline.

Objective

The aim of the study was to develop evidence-informed clinical practice recommendations on the use of bowel preparation before minimally invasive colorectal surgery, through evidence synthesis and a structured evidence-to-decision framework by an interdisciplinary panel of stakeholders.

Methods

This is a collaborative project of EAES, SAGES, and ESCP. We updated a previous systematic review and performed a network meta-analysis of interventions. We appraised the certainty of the evidence for each comparison, using the GRADE and CINeMA methods. A panel of general and colorectal surgeons, infectious diseases specialists, an anesthetist, and a patient representative discussed the evidence in the context of benefits and harms, the certainty of the evidence, acceptability, feasibility, equity, cost, and use of resources, moderated by a GIN-certified master guideline developer and chair. We developed the recommendations in a consensus meeting, followed by a modified Delphi survey.

Results

The panel suggests either oral antibiotics alone prior to minimally invasive right colon resection or mechanical bowel preparation (MBP) plus oral antibiotics; MBP plus oral antibiotics prior to minimally invasive left colon and sigmoid resection, and prior to minimally invasive right colon resection when there is an intention to perform intracorporeal anastomosis; and MBP plus oral antibiotics plus enema prior to minimally invasive rectal surgery (conditional recommendations); and recommends MBP plus oral antibiotics prior to minimally invasive colorectal surgery, when there is an intention to localize the lesion intraoperatively (strong recommendation). The full guideline with user-friendly decision aids is available in https://app.magicapp.org/#/guideline/LwvKej.

Conclusion

This guideline provides recommendations on bowel preparation prior to minimally invasive colorectal surgery for different procedures, using highest methodological standards, through a structured framework informed by key stakeholders.

Guideline registration number PREPARE-2023CN045.

Keywords: Bowel preparation, Colorectal surgery, Minimally invasive surgery, Laparoscopic surgery, Guidelines

EAES, SAGES, and ESCP rapid guideline: bowel preparation for minimally invasive colorectal resection

Stavros A. Antoniou

Publisher

European Association for Endoscopic Surgery and other interventional techniques

Guideline

Clinical Practice Guideline

Topics

Digestive Oncology Surgery

Citation

Surg Endosc 37, 9001–9012 (2023)

Published

2023

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