Introduction

EUS-guided portal pressure gradient measurement (EUS-PPGm) would be a useful procedure in patients with liver diseases (1). However, there is scarcely data on the clinical relevance of this EUS-guided procedure.

Aims & Methods

We report our experience on EUS-PPGm focus on safety, clinical relevant findings, technical drawbacks and how to overcome them.
We used a therapeutic echoendoscope and a 25G dedicated needle as previously reported (1, 2). To minimize the risk of infection, periprocedural antibiotherapy was administered and the working channel of the echoendoscope was flushed with povidone-iodine.

Results

EUS-PPGm was performed in 30 patients, median age 42±3 yo. Indications: assessment of NAFLD, 25 patients; idiopathic portal hypertension, 3 patients; evaluation for curative therapy in hepatocellular carcinoma (HCC), 2 patients. Anticoagulants were withdrawn in 4 patients. EUS-guided bilobar liver biopsies (EUS-BLB) were also immediately performed in 26 patients (87%) with a 19G needle. EUS-PPGm was successfully obtained in 25/30 patients (83%). EUS-PPGm was >5 mmHg in 14/25 cases (56%). In idiopathic portal hypertension 3/3 patients. In NAFLD 10/22 patients (45%) without endoscopic and/or ultrasonographic signs of portal hypertension and without liver fibrosis on EUS-BLB. Mean time to obtain EUS-PPGm was 21±2 minutes. Mean time for EUS-PPGm plus EUS-BLB was 45±2 minutes. Idiopathic portal hypertension was assessed by this procedure with the complementary information given by the EUS-BLB. In the 2 patients with HCC, one patient did not have reliable results and, in the other, EUS-PPGm was useful ruling out portal hypertension and the patient was referred to curative surgery that was successfully carried out.
Technical drawbacks: In 5 cases (17%) EUS-PPGm was not obtained due to non-reliable measurements in 4 cases probably due to excesive use of the elevator and up&down wheel of the echoendoscope and bending of the needle, that would be avoided. In the fifth case the EUS-PPGm was not performed for exacerbating breathing movements that precluded the procedure for safety concerns. We experienced difficulty in punctioning the hepatic and the portal vein in one and two cases, respectively, having to transverse these vessels and repositioning the needle in the lumen of these veins. In one case the 25G needle passed in close proximity to the hepatic artery. We think dedicated 25G needles have more flexibility and penetrability than larger caliber needles and, probably could lead for a safer and easier procedure and could be more accurate in the puncture of narrow vessels in liver cirrhosis (3).
Adverse events: A self-limited bleeding from the cardias was immediately observed after one EUS-PPGm in a patient with idiopathic portal hypertension. One mild epigastric pain 2 day after a combined procedure was observed. No other adverse events were registered one month later.

Conclusion

EUS-guided PPGm, even when combined with EUS-BLB, seems safe providing useful clinical information. Almost half of patients affected with NAFLD have portal hypertension diagnosed precociously in reversible stages providing a useful tool in precision Medicine, especially in the setting of obesity pandemic. Idiopathic portal hypertension was confirmed by this procedure with the complementary information provided by the EUS-BLB. In the patient with HCC, EUS-PPGm rule out portal hypertension and allowed for curative surgery. There are technical aspects related to the needle and the position of the echoendoscope that could be useful to know to improve the safety and accuracy of this procedure.

References

(1) Samarasena J, Chang KJ. Endo-hepatology: A new paradigm. Endosc Ultrasound. 72018. p. 219-22.
(2) Hashimoto R, Chang KJ. Endoscopic ultrasound guided hepatic interventions. Dig Endosc. 2021;33(1):54-65.
(3) Romero-Castro, R; Carmona-Soria, I; Jimenez-Garcia, VA; et al. Endoscopic ultrasound-guided portal pressure gradient measurement: Improving its safety overcoming technical drawbacks. Endoscopy (In press).

Disclosure

Rafael Romero-Castro is consultant to Cook Medical since February, 28th, 2023.

Introduction

Microplastics are unavoidable in our current environment and can enter the human body through ingestion, inhalation, and skin contact. Gut microbes play a role in plastic degradation, breaking down polymers into smaller molecules through enzymatic processes like depolymerization and oxidation, which can then be used as a carbon source (1). However, there is mounting alarming evidence that implicates microplastics in causing oxidative stress, DNA damage, and chronic inflammation, potentially leading to various health issues, including gastrointestinal disorders (2-4). In individuals with digestive disorders such as DGBI (disorders of gut-brain interaction), microplastics may exacerbate symptoms by disrupting gut microbiome and immune responses. Previously, within a functional dyspepsia (FD) cohort we identified a strong positive correlation between plastic degrading Exiguobacterium genus (5) within the duodenal mucosa and mucosa Th2 immune cells (6).

Aims & Methods

We aimed to investigate the differential abundance of microbes and metabolic pathways known to degrade plastics in patients with FD. Previously, we have published the 16S duodenal mucosa associated microbiome sequence data for FD (n=17) and asymptomatic control (n=11) groups (6), in addition we conducted a systematic review and retrieved 1 raw duodenal mucosa-associated microbiome 16S sequence dataset (FD n=61, controls n=38) for re-analysis with a consistent bioinformatic pipeline. This included quality assessment, demultiplexing and denoising with QIIME2 and taxonomic assignment with SILVA database. Functional differences in the microbiome were predicted with PICRUSt2. Differentially abundant plastic utilising genes were assessed in R, after CLR-transformation.

Results

As the two 16S upper gastrointestinal mucosa microbiome FD studies were sequenced separately, and the batch effect are pronounced we could not combine them for pooled analysis. When we examined the first study for predicted metabolic pathways for differential polyethylene terephthalate (PET) utilization when comparing FD patients to controls in the duodenum mucosa-associated microbiome, we did not identify any significant differences. An increase in the "partial TCA cycle (obligate autotrophs)" was observed in the gastric mucosa-associated microbiome of FD patients vs controls; PET by-products have been linked to the TCA cycle (7).
The study retrieved through our systematic review identified several significantly increased predicted functional polyethylene-associated genes, primarily from later stages of degradation. The findings revealed that the gene 3-oxoadipate enol-lactonase [EC:3.1.1.24] was significantly increased in FD patients. Furthermore, the genes 5-carboxymethyl-2-hydroxymuconic-semialdehyde dehydrogenase [EC:1.2.1.60] and 5-oxopent-3-ene-1,2,5-tricarboxylate decarboxylase/2-hydroxyhepta-2,4-diene-1,7-dioate isome were significantly increased in controls. Finally, 5-carboxymethyl-2-hydroxymuconate isomerase [EC:5.3.3.10] was also increased in controls though not significantly.

Conclusion

Our recent microbiome analysis reveals a significant enrichment of PET-degrading microbes colonising the upper gastrointestinal tract of patients with FD compared to controls. These findings provide new insights into the microbial and immune landscape of FD patients, highlighting potential microbial biomarkers and immune associations that warrant further investigation.

References

1. Yang X-G, Wen P-P, Yang Y-F, Jia P-P, Li W-G, Pei D-S. 2023. Plastic biodegradation by in vitro environmental microorganisms and in vivo gut microorganisms of insects. Frontiers in Microbiology
2. Jayavel S, Govindaraju B, Michael JR, Viswanathan B. 2024. Impacts of micro and nanoplastics on human health. Bulletin of the National Research Centre
3. Cheng Y, Yang Y, Bai L, Cui J. 2024. Microplastics: an often-overlooked issue in the transition from chronic inflammation to cancer. J Transl Med
4. Han Q, Gao X, Wang S, Wei Z, Wang Y, Xu K, Chen M. 2023. Co-exposure to polystyrene microplastics and di-(2-ethylhexyl) phthalate aggravates allergic asthma through the TRPA1-p38 MAPK pathway. Toxicology Letters
5. Parthasarathy A, Miranda RR, Eddingsaas NC, Chu J, Freezman IM, Tyler AC, Hudson AO. 2022. Polystyrene Degradation by Exiguobacterium sp. RIT 594: Preliminary Evidence for a Pathway Containing an Atypical Oxygenase. Microorganisms
6. Hoedt EC, Burns GL, Kang S, Bruce J, Morrison M, Keely S, Talley NJ. 2025. Altered Duodenal Mucosa-Associated Microbiota and Immune Profiles in Functional Dyspepsia: A Study of Host-Microbiome Homeostasis. bioRxiv doi:10.1101/2025.04.10.648308:2025.04.10.648308.
7. Carr CM, Clarke DJ, Dobson ADW. 2020. Microbial Polyethylene Terephthalate Hydrolases: Current and Future Perspectives. Front Microbiology

Disclosure

Keely reports consultancy and positions held on advisory boards for: Gossamer Bio (Scientific Advisory Board), Anatara Lifescience (Scientific Advisory Board), Microba Life Science (Consultancy) and Immuron Ltd. (Consultancy).
Talley reports personal fees from Biocodex (FD) (2024), Brown University (fiber and laxation), Microba (microbiome), outside the submitted work. NJT has a patent Licensing Questionnaires Talley Bowel Disease Questionnaire licensed to Mayo/Talley and Nepean Dyspepsia Index (NDI) 1998, patent “Diagnostic marker for functional gastrointestinal disorders” Australian Provisional Patent Application 2021901692, “Methods and compositions for treating age-related neurodegenerative disease associated with dysbiosis” US Application No. 63/537,725.

Clinical Case Summary

Amyloidosis is a systemic disease that results from the extracellular accumulation of a pathological protein - amyloid, which can be present with its light chain associated protein (AL) ^[1]. AL amyloidosis can be presented with two insoluble fibrils - the light chain immunoglobulin κ or λ. Acute liver failure with liver amyloidosis is reported extremely rarely ^[2]. Usually the symptoms of liver involvement are mild, but in rare cases acute liver failure can be noted. The characteristic clinical presentation of liver involvement is hepatomegaly, cholestasis, and jaundice ^[3].
We present a case of a 57 years old male patient admitted to Mikaelyan University Hospital, Yerevan, Armenia with jaundice, weakness, bloating and dyspnea. His past medical history is notable for bladder cancer, without distant metastasis. Upon admission, his ALP level was 722 U/L, GGT 779 U/L, ALT 37 U/L, AST 151 U/L, total bilirubin 229 umol/L, INR 2.17. Viral hepatitis serological markers were negative. Contrast computer tomography (figure 1) unveiled portal hypertension, ascites and hepatosplenomegaly with liver craniocaudal size 23 cm. A decision was made to perform a liver biopsy, which was complicated with bleeding. The liver histology(figure 2) showed positive Congo red staining and the к chain of AL amyloid was predominant to the λ chain. There was 0.25 g/L proteinuria. Serum and urine paraproteinemia tests were negative. An electrocardiogram revealed decreased voltage in all leads. Because of deteriorating condition, the patient was transferred to intensive care unit (ICU) where liver enzyme levels continued to rise, creatinine level was 430 umol/L, 24 h urine was 150 ml, total Ca level 2.9 mmol/L. Patient died 13 days after admission to the hospital.
This unusual case emphasizes that hematological diseases, like amyloidosis play an important role in liver injury, fibrosis and should be included in differential diagnosis of liver pathology.

References

1. Ueno H, Douhara A, Osaki Y, Koizumi A, Yorioka N, Ueda S, Tsutsumi M, Yoshiji H. Liver Biopsy-confirmed Primary Hepatic Amyloidosis with Only Jaundice As the Initial Symptom: An Autopsy Case Report. Intern Med. 2022 Oct 1;61(19):2877-2881. doi: 10.2169/internalmedicine.9189-21. Epub 2022 Feb 26. PMID: 35228432; PMCID: PMC9593147.
2. Kim HJ, Tomaszewski M, Lam EC, Xiong W, Moosavi S. Amyloidosis: A Rare Cause of Severe Cholestasis and Acute Liver Failure. ACG Case Rep J. 2020 Dec 4;7(12):e00479. doi: 10.14309/crj.0000000000000479. PMID: 34604435; PMCID: PMC8483873.
3. Premkumar M, Rangegowda D, Vyas T, Kulkarni A, Grover S, Mahiwall R, Sarin SK. Primary Hepatic Amyloidosis Presenting as Acute-on-Chronic Liver Failure. ACG Case Rep J. 2017 Feb 15;4:e22. doi: 10.14309/crj.2017.22. PMID: 28286788; PMCID: PMC5340654.

Figure 1- CT scan of patients abdomen.
Figure 2- Liver biopsy, Congo red positive.

Clinical Case Summary

Intestinal pseudo-obstruction (IPO) represents an unclarified dysmotility disorder featured by clinic-radiological signs of intestinal obstruction not associated with a well-identifiable organic gastroenterological disease. IPO may occur as a rare complication of autoimmune connectivopathies, including Systemic Lupus Erythematosus (SLE).
We present an SLE-affected 44-year-old man with a history of recurring nonspecific abdominal prokinetics not-responder sub-obstructive episodes.
The patient was admitted to our department for constipation, vomiting, and unintentional weight loss. Clinical examination revealed a family history of eosinophilic gastroenteritis (EG). SLE, diagnosed 5 years before with the onset of LSE-related hepatitis controlled by immunosuppressive therapy (prednisone 0.5 mg/kg/die/4 weeks; prednisone tapering + azathioprine 1 mg/kg/die/12 weeks). Except for LSE serology and malnutrition parameters, laboratory tests, including Systemic Sclerosis screening, presented no significant alterations. Radiologically, X-ray highlighted multiple air-fluid levels; contrast-enhanced CT showed fluid surrounding dilated loops, and fluid-filled ileal loops, without evidence of organic intrinsic/ab-extrinsic obstruction, perforation, or extraluminal gas.
In light of these findings, stenosing-pattern Crohn's disease (CD) and strictures-complicated EG were mainly suspected. Therefore, we confidently performed a colonoscopy with the histological examination resulting inconclusive for CD and EG. He was managed conservatively with nasogastric decompression, immunosuppressive therapy, and parenteral nutrition. Unfortunately, two weeks after, the worsening symptoms required a lifesaving right hemicolectomy with an ileostomy. Surgical histology showed an SLE fibro-inflammatory pattern, not-sparing the enteric plexus, suggestive of IPO.
IPO should be suspected in SLE patients presenting treated-unresponsive GI symptoms. Its early recognition is prognostically crucial.

References

• Downes TJ, Cheruvu MS, Karunaratne TB, De Giorgio R, Farmer AD. Pathophysiology, Diagnosis, and Management of Chronic Intestinal Pseudo-Obstruction. J Clin Gastroenterol. 2018 Jul;52(6):477-489. doi: 10.1097/MCG.0000000000001047. PMID: 29877952.
• Ohri AJ, Shah CG, Udani AH. Intestinal Pseudo-Obstruction - An Under-Recognized Presentation of Systemic Lupus Erythematosus. Indian J Nephrol. 2022 Sep-Oct;32(5):476-479. doi: 10.4103/ijn.IJN_494_20. Epub 2022 Aug 8. PMID: 36568587; PMCID: PMC9775609.
• Mok MY, Wong RW, Lau CS. Intestinal pseudo-obstruction in systemic lupus erythematosus: an uncommon but important clinical manifestation. Lupus. 2000;9(1):11-8. doi: 10.1177/096120330000900104. PMID: 10713642.

Introduction

Recurrent abdominal pain is the predominant symptom of chronic pancreatitis (CP), contributing to significant morbidity and reduced quality of life. Medical management includes analgesics, antioxidants, neuromodulators, and pancreatic enzyme replacement therapy (PERT). While PERT is used for pancreatic exocrine insufficiency (PEI), it is also thought to reduce pain by suppressing pancreatic secretion via negative feedback. However, previous meta-analysis did not show pain reduction, though subgroup analysis suggested potential pain relief with non-enteric (NE) coated enzymes1. Unlike currently available enteric-coated formulations, high in lipase but low in proteas, non-enteric coated enzymes with high protease content dissolve rapidly and may more effectively suppress cholecystokinin-mediated pancreatic stimulation, potentially improving pain outcomes.

Aims & Methods

To primarily assess the effect of a high-protease, non-enteric-coated pancreatic enzyme preparation on pain in patients with painful chronic pancreatitis. The study was registered under ClinicalTrials.gov (NCT05042284).
We conducted a randomized, double-blind, placebo-controlled trial where we randomly assigned participants to a high protease (30,000 U)-containing, non-enteric-coated enzyme preparation (n=54) and a placebo (n=53) group. The study duration was 24 weeks. Patients with painful CP (per Mayo Clinic criteria) with chronic pain were enrolled. The primary outcome was to see a difference in mean Izbicki pain score at 12 and 24 weeks and a change in pain scores (VAS 0-10) using pain diaries. Secondary outcomes were changes in the number of painful days, analgesic requirements, patient’s global impression of change (PGIC), quality of life, and adverse effects. Weekly pain data were collated. Repeated measures, linear, and mixed-effects models were used to analyze the primary outcome. Analysis was intention-to-treat.

Results

107 out of 256 screened patients fulfilled enrollment criteria. The mean age was comparable between groups (35.1±10.6 vs. 33.6±12.3 years; p=0.51), and baseline characteristics were similar. The primary outcome using mixed model analysis showed no significant differences in the change in Izbicki pain scores between the two groups at 12 and 24 weeks (Table: Results). The mean difference in VAS pain score was -3.7(95%CI: -4.3to-3.1) in enzyme group vs. -3.5(95%CI: -4.2to-2.9) in placebo group (p=0.64) at 12 weeks. The changes were -4.2(95%CI: -4.7to-3.6) vs. -4.1(95%CI: -4.7to-3.5), respectively (p=0.79), at 24 weeks indicating no significant difference. The median number of painful days was also similar, at 12 weeks, 16 (IQR: 9–35) in the enzyme group vs. 16 (IQR: 4–36.5) in placebo (p=0.31); at 24 weeks, 3(IQR: 0–8.5) vs. 3(IQR: 0–7)(p=0.30) respectively. Analgesic use was higher in the enzyme group at 12 weeks (45(83.3%) vs. 37(69.8%); p=0.11) and 24 weeks (42(77.8%) vs. 35(66%); p=0.20). Differences in the change in global health status, quality of life, PGIC, and adverse effects at both time points were also non-significant.

Conclusion

Despite the high protease content, Non-enteric coated enzyme preparations did not improve pain and quality of life in patients with painful chronic pancreatitis. Further RCTs are needed to evaluate benefits in distinct subgroups.

References

1. Yaghoobi, Mohammad, Julia McNabb-Baltar, Raheleh Bijarchi, and Peter B. Cotton. “Pancreatic Enzyme Supplements Are Not Effective for Relieving Abdominal Pain in Patients with Chronic Pancreatitis: Meta-Analysis and Systematic Review of Randomized Controlled Trials.” Canadian Journal of Gastroenterology and Hepatology. Doi: https://doi.org/10.1155/2016/8541839

Introduction

Functional dyspepsia (FD) has an estimated population prevalence of 10% using the ROME IV criteria (1). Opioids have a limited therapeutic role in the management of non-malignant pain, but the opioid prescription rates for the management of non-cancer pain has increased steadily by 0.5% per year from 2006 to 2016 (2). Opioid induced hyperalgesia is thought to contribute to the development of visceral hypersensitivity in patients with disorders of gut-brain interaction (DGBIs) (3). To our knowledge, no UK study has yet addressed the clinical characteristics and healthcare outcomes of patients diagnosed with clinically confirmed ROME IV FD who are prescribed opioids.

Aims & Methods

The primary aim of this study is to determine the proportion of patients diagnosed with ROME IV FD in a tertiary care neurogastroenterology setting who are prescribed opioids. The secondary aims of the study are as follows: to determine the differences in clinical characteristics and symptomatology between patients with FD taking opioids compared to those not taking opioids; to determine the differences in healthcare utilisation (i.e., number of investigations, clinic consultations, and hospitalisations) between patients taking opioids compared to those not taking opioids; and to determine the proportion of patients who adhere to opioid cessation advice and whether their clinical symptoms improve.
This study was approved as a retrospective audit (Nottingham University Hospitals NHS Trust registration number 21-482C). Data were analysed from consecutive patients who presented to a single tertiary care neurogastroenterology unit (Queen’s Medical Centre, Nottinghamshire, UK) between January 2016 – December 2021 and diagnosed with FD according to the Rome IV clinical diagnostic criteria. Only patients aged ≥ 18 were included and pregnancy was the only exclusion factor. Phenotype and clinical outcomes were compared between FD patients taking opioids and those not taking opioids.

Results

A total of 157 patients were diagnosed with ROME IV FD. Among these 157 patients, 34 were classified in the opioid group and the remainder (n=123) in the non-opioid group. Nausea (n=28, 82.4% versus n=75, 61%; p=0.02), vomiting (n=19, 55.9% versus n=34, 27.6%; p=0.002), and constipation (n=18, 52.9% versus n=21, 23.6%; p=0.001) were most commonly seen in the opioid group. There was no intergroup difference in the number of specialist consultations (p=0.45), or number of investigations (p=0.14) that the patients underwent. In the opioid group (n=34), 32 (94.1%) patients were advised to stop opioids. Fifteen (46.8%) stopped taking opioids on advice and nine (60%) of these patients who stopped opioids reported improvement in symptoms. The most commonly reported symptom improvement was reduced constipation (n=3, 33.3%), reduced pain (n=3, 33.3%), or general feeling better (n=3, 33.3%). Approximately half of the patients who did not stop taking opioids reported that they needed the drugs for pain relief, whilst the remaining did not provide an explanation.

Conclusion

We demonstrate that opioid intake in FD is associated with more nausea, vomiting, and constipation compared to patients who are not prescribed opioids. We also show that most patients with ROME IV FD in a tertiary care setting often do not follow opioid cessation advice. Should the burden of opioids in patients diagnosed with DGBIs be as high as this study suggests, then it is possible that an appreciable part of this disease burden may be avoidable via the strict implementation of policies to reduce opioid prescriptions for chronic non-cancer pain.

References

(1) Aziz I, Palsson OS, Tornblom H, Sperber AD, Whitehead WE, Simren M. Epidemiology, clinical characteristics, and associations for symptom-based Rome IV functional dyspepsia in adults in the USA, Canada, and the UK: a cross-sectional population-based study. Lancet Gastroenterol Hepatol. 2018;3(4):252-62.
(2) LeBrett WG, Chen FW, Yang L, Chang L. Increasing Rates of Opioid Prescriptions for Gastrointestinal Diseases in the United States. The American journal of gastroenterology. 2021;116(4).
(3) Farmer AD, Gallagher J, Bruckner-Holt C, Aziz Q. Narcotic bowel syndrome. The lancet Gastroenterology & hepatology. 2017;2(5).