Introduction

Liver and pancreas are target organs of an increased alcohol intake or impaired metabolic asset. While the correlation between liver cirrhosis and exocrine pancreatic insufficiency (EPI) is better known from literature and clinical practice, the relationship between non-cirrhotic chronic liver damage and EPI is less clear. Although studies show the role of alcohol-related hepatic steatosis and NAFLD as precursors of chronic pancreatic damage, literature is heterogeneous, discordant and lacking.

Aims & Methods

The aim of our study is to verify the frequency of EPI in patients (pts) with known diagnosis of hepatic steatosis. This is a prospective, observational, monocentric, not randomized study. Pts with known diagnosis of alcohol-related hepatic steatosis (alcohol intake > 2-3 AU/day - Group A) and non-alcoholic-related (alcohol intake < 2-3 AU/day, insulin resistance with Homa Index > 2.5, Diabetes type II - Group B) were included. All pts were submitted to a clinical questionnaire (mini nutritional assesment - MNA), clinical and biochemical evaluation (nutritional and metabolic profile), ultrasound and hepatic elastometry; evaluation of exocrine pancreatic function was made by faecal elastase (FE-1) value (EPI < 200 µg/g). Pts with known diagnoses of chronic liver damage (liver cirrhosis, viral hepatitis, autoimmune), and known diagnoses of chronic pancreatitis and/or PEI were excluded.

Results

This study included 37 pts in total, of whom 22 (59.4%) men and 15 (40.5%) women (median age of 57 yrs). Pts with alcohol intake > 2-3 AU/day (Group A) were 10 (27.2%), those with insulin resistance and type II Diabetes in oral hypoglycemic therapy (Group B) were 27 (72.9%). They were also divided according to the degree of hepatic steatosis evaluated ecographically (mild: 7 (18.9%), moderate: 15 (40.5%), severe: 5 (13.5%) and hepatic elastometry according to Metavir score (F0-F1:10 (27%), F2:25 (67.5%), F3:2 (5.4%). No pts had a nutritional and vitamin profile change, except 3 (8.1%) women with vitamin D values < 30 ng/ml. 34 (91.9%) pts had FE-1 value > 500 µg/g compatible with preserved pancreatic exocrine functionality while 3 pts (8.1%) from Group B had FE-1 value < 200 µg/g, of which only one with symptoms. There was no correlation between steatosis and hepatic fibrosis with exocrine pancreatic function.

Conclusion

In conclusion, only 8.1% of patients with hepatic steatosis had a condition of EPI. These data, despite the presence of recent studies confident in the increased frequency of EPI in patients with mainly non-alcohol-related hepatic steatosis, although still preliminary, do not show a significant relationship between hepatic steatosis and EPI. Therefore, it will be necessary to increase the study population and it will be meritorious secondary integration through radiological study with pancreatic MRI and Elasto-MRI.

Clinical Case Summary

Percutaneous endoscopic gastrostomy (PEG) tube has been frequently placed for various indications in order to provide long term enteral nutrition support[i],[ii],[iii]. Approximately 160,000 to 200,000 PEG tubes are placed each year in United States[iv]. Advancements in surgical interventions of gastrointestinal tract has resulted in increased number of anatomically altered stomachs, and so anatomically changed on endoscopic examination as well; which makes endoscopic interventions a little different[v]. Multiple case series have been reported for PEG tube placement in patients with subtotal gastrectomy [vi], however, there is scarce data available for PEG tube placement in patients with history of sleeve gastrectomy. The case that is presented here is regarding 64 years old lady with history of sleeve gastrectomy and now referred for PEG tube placement as she was advised for radiotherapy for squamous cell carcinoma of right buccal mucosa. PEG tube was successfully placed and follow up to a month showed effectively functional PEG tube with no major complications.

References

[i] Powell-Tuck J, Van Someren N. Enterostomy feeding for patients with stroke and bulbar palsy. Journal of the Royal Society of Medicine. 1992 Dec;85(12):717-9.
[ii] Richards DM, Tanikella R, Arora G, Guha S, Dekovich AA. Percutaneous endoscopic gastrostomy in cancer patients: predictors of 30-day complications, 30-day mortality, and overall mortality. Dig Dis Sci. 2013;58:768–776. doi: 10.1007/s10620-012-2397-8.
[iii] Orphanidou C, Biggs K, Johnston ME, Wright JR, Bowman A, Hotte SJ, Esau A, Myers C, Blunt V, Lafleur M, Sheehan B. Prophylactic feeding tubes for patients with locally advanced head-and-neck cancer undergoing combined chemotherapy and radiotherapy—systematic review and recommendations for clinical practice. Current oncology. 2011 Aug;18(4):e191.
[iv] Wei M, Ho E, Hegde P. An overview of percutaneous endoscopic gastrostomy tube placement in the intensive care unit. J Thorac Dis. 2021 Aug;13(8):5277-5296. doi: 10.21037/jtd-19-3728. PMID: 34527366; PMCID: PMC8411178.
[v] Morrell D, Pauli E, Juza R. Endoscopy in surgically altered anatomy. Annals of Laparoscopic and Endoscopic Surgery. 2019 Apr 24;4.
[vi] Singh P, Kahn D, Greenberg R, Indaram A, Pooran N, Bank S. Feasibility and safety of percutaneous endoscopic gastrostomy in patients with subtotal gastrectomy. Endoscopy. 2003 Apr;35(4):311-4. doi: 10.1055/s-2003-38156. PMID: 12664387.

Introduction

Primary biliary cholangitis (PBC) is a chronic autoimmune inflammatory disease of the intrahepatic bile ducts. It is characterized by chronic cholestasis, the presence of specific auto immune antibodies, and distinctive histological lesions. PBC is frequently associated with other autoimmune diseases.

Aims & Methods

This study aims to describe the clinical, biological, morphological, and histological characteristics of PBC patients with associated autoimmune diseases, as well as the therapeutic approaches used.
This was a descriptive retrospective study conducted in the Medicine C of Hepatogastroenterology Department at Ibn Sina Hospital in Rabat, including 62 patients with PBC and associated autoimmune diseases between 2010 and 2025.

Results

Among 130 patients with PBC, 62 had an associated autoimmune disease, representing a prevalence of 47%. The mean age was 47 years, with a sex ratio of 1M/9F. The most frequent symptoms were jaundice in 45.2% (n=28) of cases, asthenia in 41.9% (n=26), and pruritus in 35.5% (n=22). Clinical examination revealed signs of portal hypertension in 48.4% (n=30) of patients, jaundice in 51.6% (n=32), and scratch lesions in 19.4% (n=12).
Abdominal ultrasound showed liver with features of chronic liver disease in 71% (n=44) of patients, splenomegaly in 41.9% (n=26), ascites in 37.1% (n=23), and collateral venous circulation in 32.3% (n=20).
Biological abnormalities included cytolysis in 71% (n=44) of cases, cholestasis in 38.7% (n=24), and hepatocellular insufficiency in 22.6% (n=14). Regarding the autoimmune profile, 62.9% of PBC cases were seropositive, with anti-mitochondrial antibodies type 2 detected in 45% (n=28), anti-Sp100 antibodies in 19% (n=12), and anti-Gp210 antibodies in 16% (n=10) of patients.
Liver biopsy was performed in 40 patients and the Scheuer stages were classified as follows: stage 1 in 12.9% (n=8), stage 2 in 29% (n=18), stage 3 in 19.4% (n=12) and stage 4 in 3.2% (n=2) of cases.
Fibrosis assessment was carried out in 53 patients, using transient elastography (FibroScan) in 13 cases and liver biopsy in 40 cases. The fibrosis stage distribution was as follows: F3 in 38.7% (n=24), F2 in 25.8% (n=16), F4 in 11.2% (n=7), F1 in 8% (n=5), and F0 in 1.6% (n=1) of cases.
The main associated autoimmune diseases were autoimmune hepatitis in 40.3% (n=25) of cases and autoimmune thyroiditis in 40.3% (n=25), followed by Sjögren's syndrome in 21% (n=13), type 1 diabetes in 8.1% (n=5), and celiac disease in 4.8% (n=3). Less frequent associations included juvenile polyarthritis, Graves' disease, and vitiligo (each in 3.2% (n=2) of cases), as well as scleroderma and Addison's disease (each in 1.6% (n=1) of cases). Among these patients, 29% (n=18) had two associated autoimmune diseases, and 6.5% (n=4) had three.
All patients received ursodeoxycholic acid (UDCA) at doses of 13-15 mg/day, along with specific treatments for concomitant autoimmune diseases.
Treatment response assessment using the Paris II score showed a good response in 62% (n=38) of patients and a partial response in 38% (n=24) of patients.

Conclusion

This study confirms the high prevalence of autoimmune diseases associated with PBC, particularly autoimmune hepatitis and thyroiditis, with a strong female predominance. The most frequent stages of fibrosis were F2 and F3, highlighting the moderate to advanced disease progression at diagnosis in many patients. It emphasizes the importance of systematic screening for these comorbidities to ensure optimal management.

Introduction

The intestinal microbiota is defined as the community of microorganisms inhabiting the gastrointestinal tract, which confer benefits to the organism and play a role in immune system regulation. It has been suggested that the microbiota may play a role in the pathogenesis of gut diseases, including Celiac Disease (CeD), and the response to a gluten free diet (GFD). (1) Intestinal dysbiosis may be a contributing factor to the inflammatory state, thereby hindering resolution of symptoms and complete mucosal healing, particularly in patients who show a lack of clinical and histological improvement despite following a GFD. (2,3).

Aims & Methods

We aimed to provide a preliminary evaluation of the gut microbiota profile from diagnosis to follow-up, classifying patients who respond and do not respond to diet in order to establish a first baseline of the microbial composition and its relationship to the dietary response.
We collected fecal samples from patients enrolled at the Gastroenterology Unit of Azienda Ospedale- Università of Padova, from March to November 2024. All patients needed to be off antibiotics, probiotics and proton-pump inhibitors for at least one month before enrolment. Stool samples were collected and transferred in a buffer solution, and stored at -20°C.
Fecal samples were analyzed by BMR Genomic s.r.l. (Padua, Italy) that sequenced the V3-V4 hypervariable 16S ribosomal RNA region using the Illumina MiSeq. The results were compared to an internal population of healthy subjects (provided by BMR genomics) using Qiime2 tools. Statistical analysis was conducted using STATA 18 software. Categorical variables were compared using the Chi-square test, while non-parametric continuous variables were analysed using the Mann-Whitney test.

Results

We enrolled 71 CeD patients with mean age at diagnosis of 35.76 ± 16.29 years old (50 out of 71 were female). Of the 71 patients, 9 were newly diagnosed with CeD, while 62 were in follow-up. Among follow-up groups, 44 of 62 patients (71%) were classified as responders to diet and 18 (29%) were classified as non- responders, exhibiting classical symptoms, positive serology and histology. We compared the relative abundance of the main bacterial phyla in each sample: a significant decrease in beneficial phyla such as Actinobacteria (p = 0.04) and a decrease close to the significant threshold in Firmicutes (p = 0.06) was observed after the follow-up. This factor could be ascribed to a long-term dietary regime rather than to the disease itself. (4) Proteobacteria were more abundant in follow-up, especially in non-responders. This phylum includes many potentially pathogenic microorganisms belonging to Escherichia, Klebsiella and Shigella genera. Comparing diagnosis and follow-up patients, Clostridium perfringens was significantly more present in patients during follow-up (p=0.02), while Escherichia coli showed greater presence in patients at diagnosis (p=0.035) and in non-responders, consistently with his role in the inflammatory phase of the disease. (5)

Conclusion

Our preliminary data suggest that a long-term GFD does not always restore completely the intestinal dysbiosis present at the diagnosis and could be associated with specific alterations in beneficial bacteria. The presence of abundant Proteobacteria at diagnosis and in non-responder patients may be considered as biomarkers of active state of CeD. Future studies on various biological samples, as well as a more extensive investigation into the impact of long-term GFD, are required to highlight microbiota-immunity relationships involved in development of CeD.

References

1. Zafeiropoulou K, Nichols B, Mackinder M, et al. Alterations in intestinal microbiota of children with celiac disease at the time of diagnosis and on a gluten-free diet. Gastroenterology. 2020;159(6):2039–2051.e20.

2. Freire R, Ferreira R, Almeida LM, et al. Human gut-derived organoids provide model to study gluten response and effects of microbiota-derived molecules in celiac disease. Sci Rep. 2019;9(1):1–12

3. Schiepatti A, Montagnani M, D'Argenio V, et al. Relationship between duodenal microbiota composition, clinical features at diagnosis, and persistent symptoms in adult celiac disease. Front Microbiol. 2021;12:1–12

4. Wacklin P, Nikkilä J, Tuovinen E, et al. Altered duodenal microbiota composition in celiac disease patients suffering from persistent symptoms on a long-term gluten-free diet. Am J Gastroenterol. 2014;109(10):1587–1594

5. Olshan KL, Leonard MM, Serena G, Zomorrodi AR, Fasano A. Gut microbiota in celiac disease: microbes, metabolites, pathways and therapeutics. Expert Rev Clin Immunol. 2020 Nov;16(11):1075-1092.