Introduction

In adults with primary sclerosing cholangitis (PSC), dominant stricture (DS) develops in up to 50% of the patients (1) and is associated with an impaired long-term prognosis (2). The impact of dominant stricture (DS) on the outcomes of paediatric-onset primary sclerosing cholangitis (PSC) is unknown.

Aims & Methods

This study was aimed at investigating the impact of DS on the clinical course and prognosis of patients with paediatric-onset PSC.
We identified patients with paediatric-onset PSC diagnosed between January 1993 and May 2017 from Helsinki University Hospital records or our PSC registry. The diagnosis of PSC was made according to the EASL Clinical Practice Guidelines (3). DS was defined as a stricture with a diameter less than 1.5 mm in the common bile duct or less than 1 mm in the hepatic duct within 2 cm from the bifurcation (4). Data including clinical (i.e., presence of inflammatory bowel disease (IBD), autoimmune hepatitis (AIH) and other autoimmune diseases), laboratory markers (i.e., bilirubin, alanine aminotransferase (ALT), gamma glutamyl-transferase (GGT), carbohydrate antigen 19-9, Ca 19-9) were collected. Endoscopic retrograde-cholangiography (ERC) images were scored for severity with the modified Amsterdam PSC-score). Therapeutic interventions (i.e., need of dilatation and stenting), and cytology (i.e., biliary dysplasia andaneuploidy) were collected. The following outcomes were evaluated: biliary dysplasia, cirrhosis, liver transplantation (LT) (for all indications: decompensated cirrhosis, repeatedly confirmed biliary dysplasia and hepatocellular carcinoma), cholangiocarcinoma (CC), and/or PSC-related-death. Fisher´s exact, Wilcoxon (Mann-Whitney) tests and the fitted univariate or multiple Cox regression models to calculate hazard ratios (HR) and 95% confidence intervals (CI), for selected variables were used. In these analyses, DS was treated as a time-varying variable.

Results

We traced 68 patients (42 males) with paediatric-onset PSC (median age at diagnosis 15 years). The median follow-up was 13 years and the median age at the last follow-up was 27 years. In total 35 (51%) had concomitant AIH. DS was diagnosed in 33 patients (48%): in eight at the time of PSC diagnosis (12%) and in 25 (37%) by the end of follow-up. DS appeared on a median of 3 years after PSC diagnosis; 20/33 patients (61%) were still < 18 years at the last follow-up. Out of 33 patients with DS, 21 (64%) needed dilatations and 11 (33%) stenting. In patients with DS, two developed cirrhosis, seven were transplanted and one patient was operated on for a biliary mass with low-grade dysplasia. In patients without a DS, two developed cirrhosis, and four were transplanted; one female was excluded from survival analysis because she already had cirrhosis at the time of PSC diagnosis. Cirrhosis or biliary dysplasia or needing LT for these indications were more frequent after the development of DS (10/33, adjusted HR 4.26, 95%CI: 1.26-14.4). Also, one unit increase of log-GGT at the time of PSC diagnosis was associated with these outcomes (13/54 adjusted HR 1.78 for one unit increase of log-GGT, 95%CI: 1.04-3.05). Sex or age at PSC diagnosis, overlap with AIH, association with another autoimmune disease or IBD, bilirubin, ALT, Ca 19-9, and modified Amsterdam PSC-score at PSC diagnosis were not associated with outcomes. No CC or death occurred during the follow-up.

Conclusion

DS was present at diagnosis or developed during follow-up in about half of the patients with paediatric-onset PSC and was associated with impaired outcomes.

References

1. Björnsson E, Olsson R. Dominant strictures in patients with primary sclerosing cholangitis-revisited. Am J Gastroenterol. 2004;99(11):2281.
2. Stiehl A, Rudolph G, Klöters-Plachky P, Sauer P, Walker S. Development of dominant bile duct stenoses in patients with primary sclerosing cholangitis treated with ursodeoxycholic acid: outcome after endoscopic treatment. J Hepatol. 2002;36(2):151-6.
3. easloffice@easloffice.eu EAftSotLEa, Liver EAftSot. EASL Clinical Practice Guidelines on sclerosing cholangitis. J Hepatol. 2022;77(3):761-806.
4. Chapman MH, Webster GJ, Bannoo S, Johnson GJ, Wittmann J, Pereira SP. Cholangiocarcinoma and dominant strictures in patients with primary sclerosing cholangitis: a 25-year single-centre experience. Eur J Gastroenterol Hepatol. 2012;24(9):1051-8.

Introduction

Anti-Glycan Antibodies (AGA), gASCA (Anti-Saccharomyces cerevisiae) together with the more novel ACCA (Anti-chitobioside), ALCA (Anti-laminaribioside), and AMCA (Anti-mannobioside) are antibodies specific to Crohn’s Disease (CD) that target glycans (polysaccharides) found in microorganisms, such as C. albicans and S. cerevisiae and may alter the immune response to fungal dysbiosis. The presence of AGA in patient serum differentiates CD from ulcerative colitis (UC) and non-IBD with about 85% specificity. Moreover, concomitant positivity of 2 or more AGA increases CD specificity (>95%) and predicts faster progression to more severe disease with strictures and fistulae. This diagnostic accuracy of AGA has been validated by more than a dozen independent, peer-reviewed studies in over 4000 IBD patients.¹ More recent utilization and real-life performance of AGA in clinical practice have yet to be characterized.

Aims & Methods

We assessed the utilization and positivity of 4 AGA in 163,364 patient samples when ordered as the IBD Expanded Profile from January 2012 through March 2024. The antibodies, gASCA, ACCA, ALCA and AMCA, are detected in serum, quantitated by enzyme-linked immunosorbent assays (ELISA) using phophomannan, chitobioside, laminaribioside, and mannobioside, and reported in units where >50, >90, >60, and >100, respectively, are positive. gASCA utilizes an improved purified form of mannan and is comparable to conventional ASCA.

Results

Of a total of 163,394 patient samples, one quarter (25.2%) were positive for at least one AGA. Isolated positivity of only one AGA was found in 18.3% where gASCA alone was the most common (7.0%) followed by AMCA (6.1%). Concomitant positivity of 2 or more AGA occurred in only 7.0% of all samples with the most frequent co-occurrences, ALCA + AMCA and AMCA + gASCA. Individual AGA frequencies were gASCA (11.3%), AMCA (11.3%), ALCA (7.2%), and ACCA (4.3%). Median antibody levels (interquartile range) for positive samples were: gASCA 66.0 (57.0-84.0), ACCA 124.0 (104.0-167.0), ALCA 76.0 (67.0-92.0) and AMCA 147.0 (118.0-205.0).

Table 1. Anti-Glycan Antibodies in 163,394 Patient Serum Samples

Conclusion

Serum AGA were frequently positive in over 160,000 patient samples. One quarter (25.2%) of all samples were positive for at least one AGA supporting their potential usefulness in differentiating CD from UC and non-IBD. Most positivity (18.3%) occurred as one isolated positive AGA (~85% specific for CD). A smaller subset, 7.0%, had 2 or more AGA and as such, are associated with a very high specificity (>95%) for CD as well as an odds ratio of 3 for severe disease and need for abdominal surgery.^1,2 Of note, most samples (88.7%) were seronegative for gASCA, reiterating the limited sensitivity of conventional IBD serology (only pANCA and ASCA). Of 144,864 gASCA-seronegative samples, a substantial number, 18,533 (13.9%), were positive for one or more of the novel AGA (ACCA, ALCA or AMCA). This result substantiates the potential incremental benefit of these novel Anti-Glycan Antibodies in identifying those patients more likely to have CD and its​​​​​ disease complications.

References

1. Bonneau J, et al. Systematic review: New serological markers (anti-glycan, anti-GP2, anti-GM-CSF Ab) in the prediction of IBD patient outcomes. Autoimmunity Reviews 2015;14:231-245.
2. Kaul A, et al. Serum Anti-glycan Antibody Biomarkers for Inflammatory Bowel Disease Diagnosis and Progression: A Systematic Review and Meta-analysis. Inflamm Bowel Dis 2012;18(10):1872-1884.

Introduction

Helicobacter Pylori (H. Pylori) is present in about half of the world's population and it is the leading cause of infection-related cancers, including gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. Various studies have shown that H. Pylori is highly prevalent in Albania.

Aims & Methods

The aim of this study is to evaluate presence of H. Pylori infection in patients with gastric cancer with the purpose of providing insights for clinical management and treatment decisions. This was a single-center prospective study, conducted at University Clinic of Gastrohepatology at the University Hospital Center Mother Teresa in Tirana, Albania from 2021 to 2022. The study included patients presented at our endoscopy unit that were diagnosed with gastric neoplasm, without any history of familial or hereditary cancer. Demographic, clinical, radiological and laboratory data were collected for each patient. Based on tumor histology they were divided in two groups: gastric adenocarcinoma and lymphoma. We studied the presence of Helicobacter Pylori infection in patients with gastric cancer and its association with the histological, clinical and laboratory characteristics of these patients. The data were analyzed using SPSS statistical package version 23.0.

Results

A total of 50 patients 32 (64%) male and 18 (36%) female with a mean age of 64.5 ± 11.8 years [38-85] were included in this study. 92% had gastric adenocarcinoma while only 8 % had gastric lymphoma. Helicobacter pylori was found present in 82% of the studied patients. Among the histopathological forms, the presence of H. pylori was predominantly observed in 100% (4 patients) of lymphomas and 80 % (37 patients) of adenocarcinomas (93.8% of patients with moderately differentiated adenocarcinoma). No significant association was observed between the presence of H. pylori infection and histopathological diagnosis (p = 0.33) or staging (p = 0.358). However, the presence of H. pylori infection was significantly associated with a higher incidence of distal cancer compared to proximal cancer (60% vs 12%; p = 0.002. Furthermore, the average levels of CEA were significantly higher in patients with adenocarcinoma compared to lymphoma (p = 0.035).

Conclusion

Our study demonstrated that Helicobacter pylori infection is highly prevalent among patients with gastric cancer, with a higher incidence observed in patients with distal cancer compared to proximal cancer. However, no significant association was observed between the presence of H. pylori infection and histopathological diagnosis or staging. CEA levels were found to be significantly higher in patients with adenocarcinoma compared to lymphoma, which may indicate its potential utility as a diagnostic marker. These findings may have implications for the management and diagnosis of patients with gastric cancer.