Introduction

Amyloidosis describes a group of diseases caused by the extracellular accumulation of misfolded serum proteins. Amyloidosis can affect all organs including the gastrointestinal (GI) tract. Symptoms like nausea, vomiting, diarrhoea, and abdominal pain suggest GI involvement of amyloidosis. Furthermore, GI amyloidosis is associated with a higher risk of gastrointestinal bleeding, especially when mucosal lesions are present.

Aims & Methods

Our study aimed to evaluate the frequency of GI manifestations in patients with amyloidosis, characterize these patients clinically, and describe the endoscopic and histopathologic findings in GI amyloidosis. A retrospective study was conducted at a German University Hospital, including a cohort of 61 patients with different types of amyloidosis between January 2004 and June 2022. Clinical, endoscopic, and histopathological data were retrieved from medical records and analysed.

Results

61 Patients with different types of amyloidosis were included in the study cohort. 23 (37.7%) displayed GI involvement. The median age of the patients with amyloidosis and gastrointestinal manifestation at diagnosis was 62 ± 18.28 years. 60.9% were male. Among the amyloidosis types, 52.5% were amyloid light chain (AL), 21.7% were transthyretin (TTR), 13.0% showed amyloid A (AA), and in 18% of the cases, the type was unknown. The gastrointestinal organs affected were mainly the colon (65.22%), stomach (30.4%), rectum (30.4%), duodenum (26.1%), and ileum (21.7%). Initial gastrointestinal symptoms were present in 78.3% of the patients and included mainly diarrhoea (34.8%), abdominal pain (30.4%), weight loss (26.1%), nausea/vomiting (21.7%), and loss of appetite (17.4%). Endoscopic findings were ulcerations (47.8%), mucosal inflammation (43.5%), polyps (26.1%), erosions (13.0%), vascular malformation, polypoid protrusion, submucosal haematoma, erythema, metaplasia, and diverticulum. Histopathological findings included thickening of the vessel walls, (peri-)vascular and interstitial amyloid deposits, and in one patient, a polyp with amyloid deposits. GI bleeding occurred in 39.1 % of the patients during the course of the disease. The mortality rate 5 years after diagnosis was 30.4%.

Conclusion

Amyloid tends to deposit in the gastrointestinal tract, which, being easily accessible, is often the target organ for a pathological diagnostic examination. However, amyloidosis of the gastrointestinal tract, with biopsy-proven disease, is rare. Due to the low incidence of this disease, the diagnosis of gastrointestinal amyloidosis may be overlooked. Furthermore, considering the existing literature, there is a paucity of data on GI amyloidosis. Therefore, clinicians must be aware of this manifestation when treating patients with amyloidosis, and if suspected, endoscopy with biopsy and histopathological examination should be performed.

Introduction

​Routine mucosal sampling from pre-defined anatomical sites is recommended during pediatric upper gastrointestinal endoscopy regardless of macroscopic appearance, but evidence for this recommendation remains limited. We investigated this issue in a large and well-defined patient cohort.

Aims & Methods

Concordances between endoscopic and histologic findings and their association to the diagnosis after the first endoscopy was studied in 1181 consecutive children undergoing endoscopy with systematic biopsy sampling during years 2007-2014. Furthermore, the associations between endoscopic and histologic findings and a gastrointestinal diagnosis received during follow-up up to 11 years were studied.

Results

Systematic sampling was conducted in 98.4% of the children in esophagus, 99.3% in stomach, and 98.8% in duodenum. Any endoscopic findings were reported in 51.7% and histologic abnormalities in 59.3% of the children. The Cohen’s k coefficient between endoscopic and histologic findings was 0.272 overall, 0.190 in esophagus, 0.148 in stomach, and 0.520 in duodenum. The most common diagnoses were celiac disease (26.0%), inflammatory bowel disease (11.2%) and gastroesophageal reflux disease (5.2%). Significant association between endoscopic abnormalities and presence of a diagnosis was seen in any endoscopic site and in duodenum, but not in esophagus or stomach, while histologic abnormalities associated with a diagnosis in each biopsy location (Table 1.). Histologic abnormalities were seen in 146 (25.4%) children without diagnosis at the first endoscopy, the most common being chronic inactive gastritis (7.5%) and mild chronic esophagitis (5.8%). Furthermore, in patients without initial diagnosis histologic abnormalities were associated with a follow-up diagnosis (odds ratio 2.59, 95% confidence interval 1.40-4.79), whereas endoscopic abnormalities did not (OR 0.61, 95% CI 0.31-1.18).

Conclusion

The low concordance between endoscopic and histologic findings supports systematic biopsy sampling in pediatric upper gastrointestinal endoscopy. Histologic findings are strongly associated with initial gastrointestinal diagnosis and to a lesser extent with a follow-up diagnosis.

Disclosure

Author has no conflict of intrest

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

SLC10A1 codes for the sodium-taurocholate cotransporting polypeptide (NTCP), which is a hepatocellular transporter for bile acids. It is expressed in the basolateral membrane of hepatocytes, functioning to uptake bile acids from plasma. Bile acids are essential for the absorption of lipids and lipid-soluble nutrients from the intestine. SLC10A1 mutations impair the NTCP function and cause elevated levels of total bile acids in the plasma, leading to hypercholanemia.
We report the case of a 25-year-old male patient who presented to our emergency department with a three-week history of pruritus and progressive jaundice. Laboratory tests revealed elevated levels of bilirubin, alanine aminotransferase and aspartate aminotransferase as well as alkaline phosphatase. Gamma glutamyl transferase was normal. A viral cause was excluded. Bile acids in serum were elevated. The magnetic resonance cholangiopancreatography showed some biliary irregularities but not typically for primary sclerosing cholangitis. Liver biopsy excluded an autoimmune disease but revealed canalicular cholestasis. Genetic testing was performed, and a homozygous mutation of SLC10A1 gene was identified. A thorough anamnesis revealed that the patient was born from a consanguine marriage. Due to progressive pruritus and jaundice, we started an off-label therapy with an ileal bile acid transport inhibitor, which improved clinical symptoms and laboratory parameters.
Little is known about bile acid transporter defects on the basolateral side of hepatocytes. To date few case reports are published. Due to the variety of gene mutations, clinical manifestations of genetic intrahepatic disorders are diverse. With this case we want to highlight the importance of early genetic testing in patients with progressive hyperbilirubinemia of unknown origin. To enable a liver transplantation, patients with progressive intrahepatic cholestasis underlying a genetic cause should always be referred to a liver center.

Introduction

Acute upper gastrointestinal (UGI) bleeding is a common medical emergency among the elderly. There is limited data on the management and outcomes of non-variceal UGI bleeding in the elderly in India.

Aims & Methods

We aimed to study clinical presentation, endoscopic findings, and outcomes in elderly patients with acute non-variceal UGI bleeding. All elderly patients (≥ 60 years of age) who presented with acute UGI bleed and were admitted for the same from 2021 to 2022 were retrospectively analysed. Baseline characteristics, blood transfusions before and after endoscopy, endoscopic diagnosis and therapy, AIMS65 score, complete Rockall score, and outcomes such as in-hospital re-bleeding and mortality were recorded.

Results

Of the 399 patients who had acute non-variceal UGI bleed, 309 patients aged <60 years were excluded. Of the 90 patients studied, the mean age of presentation was 69.8 ± 7.35 years, with 81.1% males. The most common presentation was melena (30%). Forty-one (45.5%) patients had a history of antiplatelet and anticoagulant use. The most common endoscopic finding was gastric ulcer (54.4%), followed by duodenal ulcer (22.2%), gastroesophageal junction ulcer (7.7%), Mallory-Weiss tear (6.6%), duodenal diverticular bleed (2.2%). The majority of ulcers were Forrest III (43.3%), followed by Forrest IIa (23.3%) and IIc (18.3%). Around 65% of patients with non-variceal UGI bleeds did not require endotherapy. Dual endotherapy was done in 25.5.5% of patients. Triple endotherapy was done in two patients. AIMS65 score was 1 in 50% of patients and 2 in 24.5% of patients. The majority (81.1%) of patients had a complete Rockall score of 3-7, indicating a moderate risk of re-bleeding and mortality. All the 90 patients were discharged without any mortality.

Conclusion

Our study showed that gastric ulcer was the most common cause of acute non-variceal UGI bleeding in the elderly, and melena was the most common presentation. Early endoscopic therapy may reduce blood transfusion requirements, in-hospital re-bleeding, and mortality.

Introduction

Sepsis is a life-threatening condition characterized by organ dysfunction resulting from a dysregulated host response to infection. A defining feature of sepsis is the presence of bacteria in the bloodstream or the translocation of intestinal microbes to distant organs such as the lungs. Many of these pathogens originate from the intestinal microbiota. The intestinal mucosa serves as a critical barrier, and its damage or dysfunction is considered a central factor enabling bacterial invasion and systemic spread during sepsis.

Aims & Methods

This study aims to characterize sepsis-induced dysfunction of the intestinal barrier. Specifically, we investigate whether, and how, the functions of the gastrointestinal epithelial barrier are modulated by different sepsis-causing bacterial strains. To this end, an in vitro model was developed using intestinal epithelial cell lines (HCT-116 and Caco-2) co-cultured with bacterial isolates. These isolates, representing diverse sepsis etiologies, were obtained from the blood of septic patients. The impact of bacterial interaction on epithelial integrity was assessed by quantifying the protein levels of E-cadherin and Occludin using Western blot analysis.

Results

Co-culture with sepsis-associated bacterial strains led to the disruption of epithelial cell-cell junctions. Specifically, Escherichia coli strains BK10478, BK01267, and BK06223, at a multiplicity of infection (MOI) of 5, induced a marked downregulation of both Occludin (a tight junction protein) and E-cadherin (an adherens junction protein) in HCT-116 cells. Notably, only a subset of these strains elicited similar effects in Caco-2 cells. Some bacterial isolates had no detectable impact on junctional protein expression in either cell line, highlighting strain-specific and cell-type-dependent responses.

Conclusion

Sepsis is a heterogeneous syndrome characterized by complex host-pathogen interactions. Our findings reveal that the ability of sepsis-associated E. coli strains to compromise epithelial cell-cell junctions is both strain-specific and dependent on the epithelial cell type. Given the essential role of barrier integrity in preventing bacterial translocation, these results provide novel insights into sepsis pathogenesis and underscore the therapeutic potential of strategies aimed at preserving or restoring epithelial barrier function.

Introduction

COVID-19, as a systemic disease, critically affects the liver and biliary system. Secondary sclerosing cholangitis (SSC) is an increasing complication in critically ill patients. After severe COVID-19 infection, the occurrence of bile duct changes resembling the picture of SSC has been increasingly observed. The early prognosis of COVID-19-associated SSC has not been adequately studied.

Aims & Methods

The aim of this study is to investigate the effects of COVID-19 on the liver in relation to previous hepatic disease, as well as to identify early prognostic markers for the course of disease in patients and the development of any complications. 261 patients treated in intensive care units of the University Hospital Regensburg and suffering from COVID-19 were analyzed in different groups. The classification was based on the presence and type of previous hepatic disease. Laboratory and clinical parameters collected during hospitalization included values at the time of admission and maximum values that developed during hospitalization. These were evaluated concerning mortality rates and the development of COVID-19-associated SSC in the different patient groups.

Results

Patients with pre-existing chronic liver disease had a hazard ratio for death of 2.045 (p=0.0446) compared to patients without chronic liver disease. The hazard ratio for death was higher for patients with pre-existing chronic liver disease than for patients with malignant disease (HR=1.986, p=0.0135) or dialysis requirement on ICU admission (HR=1.732, p=0.034). In all groups, mortality was also significantly correlated with an increase in liver enzymes during hospitalization. High bilirubin (p=0.002) or INR (p=0.018) levels on admission also correlated with increased mortality, independent of pre-existing hepatic disease. Among the entire cohort, the cause of death was associated with COVID-19 in 90.8%. In addition, the risk of developing COVID-19-associated SSC increased with the duration of ECMO therapy and correlated significantly (p=0.004) with high AP levels on admission.

Conclusion

This study demonstrates the potent effects of COVID-19 on the liver and biliary system and potential complications in patients with and without pre-existing chronic liver disease. Bilirubin and INR could serve as predictive factors for mortality. AP could be considered an early predictor for the development of COVID-19-associated SSC in patients with COVID-19. In the future, this will provide crucial clues for an optimized treatment strategy, including ventilation and sedation.