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.

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.

Introduction

EUS-guided gastroenterostomy(EUS-GE) with lumen-apposing metal stent(LAMS) has emerged as a mini-invasive, effective and safe alternative to surgical gastrojejunostomy and endoluminal stenting to treat malignant gastric outlet obstruction(MGOO).Currently, intra-abdominal carcinomatosis represents a relative contraindication to this procedure, due to a possible higher risk of clinical failure.

Aims & Methods

The primary aim was to compare clinical success of EUS-GE in patients (pts) with MGOO with vs without concomitant intra-abdominal carcinomatosis.Secondary aims was to compare between the same subgroups of pts the clinical and procedural characteristics, the technical success rate and long-term outcomes.All pts undergoing EUS-GE for MGOO at our institution from Jun.2018 to Dec.2024 were retrospectively enrolled.Technical success was defined as successfully establishing EUS-GE and clinical success as oral diet tolerance without re-intervention for 14 days after the procedure. Inclusion criteria: 1)age>18 years; 2)MGOO; 3)complete clinical records. Exclusion criterium:missing data. Intra-abdominal carcinomatosis was defined according to CT/MRI imaging. Adverse events (AEs) recorded and classified (AGREE). Obstructive symptoms graded according to the GOOSS score. Data expressed as median [range], comparisons by the Student-t-test, Mann-Whitney-u test and X² test as appropriate.

Results

EUS-GE for MGOO was performed in 74 pts (36 [48.6%] males, age 71 [30-92]), with ECOG performance status ≥2 in 29(39.2%). Obstructive symptoms were reported by 72(97.3%) pts (GOOSS: 1 [0-3]). Intra-abdominal carcinomatosis was present in 29(39.2%) pts. Ascites was more frequent in pts with vs without carcinomatosis (19[65.5%] vs 12[26.7%], p=0.02). Other clinical characteristics were comparable between groups.All EUS-GE were performed in deep sedation. LAMS included Axios and Spaxus (Axios: 37[82.2%] vs 25[86.2%],p=0.89). 20mm LAMS were used in a comparable proportion of pts with vs without carcinomatosis (25[86.2%] vs 37[83.2%], p=0.89). Technical success rates and procedural time did not differ between groups (28[96.6%] vs 43[95.6%],p=0.69; 33[16-85] vs 40[20-106],p=0.52). Overall, 9 misdeployments were observed (carcinomatosis: 3[10.3%] vs no-carcinomatosis: 6[13.3%], p=0.98). AEs were 4 (19.8%) and 9 (20%) in pts with vs without carcinomatosis (p=0.71), all grade III. Time to refeeding (days) was comparable between groups (1[1-5] vs 1[1-5], p=0.96), while hospital stay (days) was longer in patients with carcinomatosis (8[2-18] vs 4[2-15],p=0.0009). Clinical success rate did not differ in pts with vs without carcinomatosis (25[86.2%] vs 43[95.6%],p=0.31). All 6 failures were due to malignancy progression. Median follow-up duration was 51[21-622] days. During follow-up, 27(93.1%) pts with and 38(84.4%) without carcinomatosis died(p=0.45). Median survival (days) and oral diet toleration until last follow-up/death were comparable between pts with vs without carcinomatosis (42[21-398] vs 66[26-622],p=0.07; 26[89.6%] vs 42[93.3%],p=0.89). Oncological treatments were resumed in 11(37.9%) pts with and 23(51.1%)without carcinomatosis (p=0.38). Rehospitalization rate for any cause was comparable in both groups (14[48.3%] vs 26[57.7%],p=0.57), requiring reintervention in 1case.

Conclusion

In our study population high technical and clinical success rates of EUS-GE were comparable in pts with and without intra-abdominal carcinomatosis. The major outcomes were comparable between these 2 subgroups of pts, suggesting the long-term efficacy of this procedure also in those with more advanced malignancy.

Clinical Case Summary

We present a case of a 46-year-old female admitted to our clinic with a 6day history of nausea, vomiting around 10-15 times with blood clots, heartburn, regurgitation, retrosternal pain, loss of appetite, dizziness, generalized weakness, jaundiced skin and sclerae. The patient had previously been diagnosed with left-sided ulcerative colitis, currently in remission without medications. She mentioned alcohol abuse of around 300ml cognac per day for the past 2 years.
Physical examination t=36,6 ^oC, BP=70/40 mm Hg. Blood tests showed macrocytic anemia, thrombocytopenia, hypokalemia, elevated values of total bilirubin, especially direct, ALT, AST, GGT, and ALP, creatinine, urea, low albumin level and coagulopathy.
EGDS showed circumferential black discoloration of the esophagus, which bled on contact (Gurvits syndrome or black esophagus) and a coffee grounds resembling sediment in the stomach. PPI therapy was initiated.
An abdominal ultrasound found hepatomegaly, vena portae=11mm. A diagnosis of alcohol-related liver disease was made and corticosteroid therapy was initiated (32mg methylpredinosolone/day). Maddrey’s Discriminant Function was 41.9, and Lille score after 7 days of corticosteroid treatment was 0.021. Steroid therapy was continued, with an increase in serum creatinine levels. A diagnosis of AKI was made, and the patient was started on hemodialysis. Hallucinations started a few days after the initiation of hemodialysis. The differential diagnosis panel included hepatic, uremic, and Wernicke encephalopathies, which were deemed unlikely based on normal serum ammonia levels, unchanged status on hemodialysis, and absence of ataxia, nystagmus and confabulation, respectively. The patient was subsequently transferred to the intensive care unit, where the hallucinations were successfully treated with benzodiazepine therapy. Alcohol withdrawal syndrome was confirmed. A probable diagnosis of pre-renal injury was confirmed, although renal injury could not be ruled out.

Clinical Case Summary

A 38 year old female with jaundice, multiple limb bruises and a left breast haematoma on a background of decompensated alcohol related cirrhosis, presented to our hospital’s emergency department in December 2024 with spontaneous oropharyngeal bleeding. There was no history of any oropharyngeal infections, trauma, tongue bite or alcohol withdrawal seizure. She lost a litre of blood in a four-five hour period following her presentation in the emergency department. Initial interventions by ENT surgery team and Maxillofacial surgery teams proved unsuccessful in achieving definitive haemostasis in the glossal bed. This resulted in airway compromise which was managed by intubation by the anaesthetics team. Following input from the interventional radiology team, patient underwent angiograms of the right and left external carotid and common carotid arteries and a vascular blush was identified. She underwent successful embolization of the right sided facio-lingual and left sided lingual vessels and haemostasis was achieved.
Patient remained intubated in ITU and received management for ongoing coagulopathy and hepatic encephalopathy. Following step down to the Gastroenterology ward, extensive dietitian, physiotherapy, speech and language therapy input was required. She achieved baseline status after one month of extensive medical management and her cognitive function improved. She was eventually discharged to a rehabilitation assessment bed.
Spontaneous lingual artery haemorrhage is a rare manifestation of coagulopathy secondary to cirrhosis with other cases in literature stemming mainly from a co-existing asymptomatic pseudoaneurysm. This case illustrates an atypical presentation of decompensated liver cirrhosis with an acute spontaneous lingual artery haemorrhage requiring embolization of bilateral facio-lingual vessels. It emphasizes the need for early joined up multidisciplinary care and intervention to achieve haemostasis and a successful outcome in these patients.

Disclosure

The authors declare no conflict of interest