Introduction

​​​​​PSC is chronic infammatory disease of bile ducts leading to strictures of bile duct and eventually to liver cirrhosis. Chronic inflammation is associated with markedly increased risk of cholangiocancer (CCA). In addition, gall bladder abnormalities are common in patients with PSC¹ such as cholecystitis, gallstones, polys and gallbladder carcinoma (GBCA). Increased fasting gallbladder volume has been reported with normal gallbladder emptying². Due to the increased risk of GBCA³ cholecystectomy is recommended in PSC with gallbladder polyps ≥8 mm and smaller polyps growing⁴. However, cholecystectomy has been associated with impaired PSC outcome. A study consisting of 11 PSC patients with cholecystectomy suggested protective role of gallbladder based on MRCP changes and elevated AST levels in patients with cholecystectomy. No significant difference in serum bile acids was observed in patients with or w/o cholecystectomy⁵. Another small study including five PSC patients with cholecystectomy showed that cholecystectomy was associated with worse Mayo scores and an elevated FIB4⁶. More than 50% of PSC have enlarged gallbladder which is suspected to be caused by hyperpressure in the biliary tract⁵. Cholecystectomy may thus eliminate this reserve function and lead to progression of bile duct strictures.

Aims & Methods

To evaluate the impact of cholecystectomy on liver enzyme levels, biliary bile acid composition, bile duct disease progression, and overall outcomes in a large PSC patient cohort, we analyzed data from 1,009 individuals enrolled in the prospective Helsinki PSC registry. Of these, 114 patients (11.3%) had undergone cholecystectomy—34 prior to and 80 following the PSC diagnosis. Patients with gallbladder cancer were excluded. Clinical and laboratory parameters were collected, along with data on disease progression based on sequential ERC examinations scored by the Helsinki ERC score⁷. Additionally, bile composition was analyzed in a subgroup of 157 patients receiving UDCA therapy, 32 of whom had undergone cholecystectomy.

Results

Demographics, liver function tests, and outcomes stratified by cholecystectomy, are presented in the table. We found no differences between the three groups (no cholecystectomy, cholecystectomy done prior or after PSC dg) regarding the progression of bile duct disease or its severity, liver function tests, development of biliary dysplasia or need for dilatation, Mayo- and MELD-scores. The cumulative incidence of the composite end point (= transplantation, liver related death, HCC or CCA) did not differ between groups. The molar-% of phospholipids were lower and cholic acid and deoxycholic acid (mg) elevated in bile in patients with cholecystectomy, whereas no differences were found in UDCA content.

Conclusion

In this large study investigating the impact of cholecystectomy on PSC outcomes, we found no effect on liver enzyme levels, prognostic indices, bile duct disease progression, or overall prognosis, regardless of whether the procedure was performed before or after the PSC diagnosis.

References

1. Said K, eta al. Journal of Hepatology 2008; 48:598–605
2. Said K, et al. World J Gastroenterol 2009; 15: 3498-3503
3. van Erp LW, et al. Liver Int 2020; 40:382–92.
4. Chazouilleres O et al. EASL Clinical Practice Guidelines on sclerosing cholangitis. J Hepatol 2022; 77:761–806
5. Cazzagon N, et al. JHEP Reports 2023. https://doi.org/10.1016/j.jhepr.2022.100649
6. Miyake N, et al. Cureus 17(3): e80184. DOI 10.7759/cureus.80184
7. Boyd S, et al. Endoscopy. 2016;48:432-9.

Introduction

Metaplasia refers to the emergence of cells not normally present in a given organ, typically as a result of chronic inflammation. While often linked to cancer development, its role in inflamed epithelium remains unclear. Paneth cell metaplasia (PCM) is a phenomenon in which Paneth cells, normally restricted to the small intestine, appear ectopically in the inflamed colonic epithelium of patients with ulcerative colitis (UC). However, the roles and characteristics of PCM in the inflamed colonic mucosa remain poorly understood. This study aimed to characterize the clinical and molecular features of colonic PCM and investigate its functional role in the inflamed epithelium.

Aims & Methods

We first analyzed the clinical characteristics of PCM using biopsy samples and clinical data from UC patients who underwent endoscopic evaluation at our institution. To elucidate the molecular features of colonic PCM, we employed spatial transcriptomics to compare PCM in the colon with Paneth cells in the small intestine from the same individuals. These findings were validated in a knockout mouse model, murine colonic organoids, and patient-derived human colonic organoids. This multi-model approach allowed us to investigate the mechanisms underlying PCM formation and assess its functional relevance in intestinal epithelial biology.

Results

PCM was predominantly observed in the left-sided colon and was associated with longer disease duration and the presence of pathological inflammation. Spatial transcriptomic HD analysis suggested that colonic PCM emerges within an inflammatory microenvironment distinct from that of the small intestine. Notably, the expression of the Wnt target genes HD5 and HD6, which are typically required for Paneth cell differentiation in the mouse small intestine, was reduced in colonic PCM. In contrast, expression of REG3A, a gene known to be induced by the inflammation-associated cytokine IL-22, was maintained. Consistent with previous reports highlighting the role of IL-22 in the differentiation and maturation of human Paneth cells, these findings suggest that IL-22 may contribute to the induction of PCM under inflammatory conditions. Mechanistically, IL-22 was shown to suppress Notch signaling in human colonic organoids, thereby promoting PCM formation and inducing REG3A expression in metaplastic cells. In vitro experiments using mouse colonic organoids demonstrated that Reg3a enhances epithelial cell proliferation and promotes wound healing. In vivo, Reg3a^ΔIEC mice exhibited impaired wound healing in both acute and chronic DSS-induced colitis models. Furthermore, REG3A treatment of human colonic organoids derived from UC patients stimulated epithelial proliferation and accelerated wound closure.

Conclusion

PCM contributes to epithelial protection in UC by promoting REG3A-mediated regeneration. These findings suggest that PCM may play a compensatory role in mucosal healing during colonic inflammation.

Introduction

Standard treatment of autoimmune hepatitis (AIH) typically includes a combination of azathioprine and corticosteroids. However, approximately 20% of patients do not respond well to this conventional therapy. In this scenario, mycophenolate mofetil (MMF) may be used as an alternative treatment for patients with intolerance or non-response to first-line options.

Aims & Methods

This study aims to evaluate the performance of MMF in intolerant or non-responders patients with AIH previously treated with conventional therapy. We performed a systematic review in PubMed, Embase, and Cochrane databases. We analyzed overall remission, remission at AZA intolerance, and remission at AZA non-response. We also compared the outcome of overall remission in patients with AZA intolerance vs. AZA non-response. Statistical analyses were performed using R language 4.3.1.

Results

21 studies and 646 patients were included. The pooled overall remission rate was 62.21 (95% CI 54.31, 70.10). We found an overall remission rate of 66.74 (95% CI 57.48, 76.00) in patients intolerant to AZA, and 27.80 (95% CI 11.56, 44.04) in AZA non-responders. The comparison of overall remission in both groups favored the intolerance group (OR 4.98; 95% CI 1.69, 14.72; p = 0.004).

Conclusion

MMF is effective in inducing remission in patients with AIH who failed the first-line treatment. The overall effect is more prominent in patients who failed conventional therapy due to intolerance. Non-response to AZA may be correlated to suboptimal response to MMF as well.

Introduction

The prevalence of musculoskeletal disorders (MSD) among gastroenterologists is estimated between 39 to 89%. Factors associated with MSDs among endoscopists include a high number of procedures (over 20/week), prolonged procedure times (over 16 hours/week), the age of the endoscopist (> 40 years vs ≤ 40 years), and female sex.
This study aimed to evaluate the prevalence of MSD among French gastroenterologists and identify risk factors of MSD

Aims & Methods

A computerized, anonymized questionnaire was e-mailed to all members of French society of endoscopy (SFED) over a one-month period. Demographic data were collected, as well as the level of endoscopic activity performed, the quantity and volume of endoscopies performed per week, the presence of pain associated with the practice of endoscopy, and an assessment of stress.

Results

485 gastroenterologists responded to the questionnaires, the majority were male (55%), with a median age of 48 years (IQR 37–60), and 45.6% practiced endoscopy for more than 20 years. 74.3% of respondents worked full-time, mostly in private practice (47% in private practice, 13% in mixed public-private practice). Endoscopy was performed for a median of 15 hours per week (IQR 10–18.8), with 24 procedures per week (IQR 15–30).
76.3% of participants had already experienced joint and/or musculoskeletal pain related to work. Pain complaints mainly concerned the lower back (55%), shoulders (36% left, 37% right%), neck (50%), and wrists (30% both side). More than half of the participants (55.9%) reported that the pain persisted after procedures, with 17.8% experiencing nocturnal pain and about a quarter reporting pain lasting more than 3 months.
The impact of MSD on workload was evaluated. 5.1% of the gastroenterologists reported loss of efficiency, 3,8% adapted their job, 2.4% decreased their activity, and 2.1% had work stoppage. 35% declared to have management of their MSD (28.1% painkiller, 23.2% reeducation, 3.5% surgery). To reduce discomfort, 74.7% of respondents reported using an adjustable-height examination table, and half adjusted the height and distance of the screen.
In multivariate analysis, factors associated with MSD were, femal sexe (OR 1.85 (1.15-3.01) p = 0.012, number of endoscopy (OR 1.05 (1.01-1.11) p=0.03, activity > 20 years (OR 2.42 (0.89, 6.47) p=0.079.) The risk of MSD was higher after 16.5 hours of endoscopy/ week (Se 35%, Sp 83%).

Conclusion

Musculoskeletal pain among French gastroenterologists is common and concerning. Therefore, it is essential to develop preventive programs to support their health and ensure the quality and safety of care.