A novel serum metabolomic panel distinguishes IgG4-related sclerosing cholangitis from primary sclerosing cholangitis.

BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) and IgG4-related sclerosing cholangitis (IgG4-SC) are chronic fibro-inflammatory immune-mediated hepatobiliary conditions that are challenging to distinguish in a clinical setting. Accurate non-invasive biomarkers for discriminating PSC and IgG4-SC are important to ensure a correct diagnosis, prompt therapy and adequate cancer surveillance. METHODS: We performed nuclear magnetic resonance (NMR)-based metabolomic profiling using serum samples collected prospectively from patients with PSC (n = 100), IgG4-SC (n = 23) and healthy controls (HC; n = 16). RESULTS: Multivariate analysis of the serum metabolome discriminated PSC from IgG4-SC with greater accuracy (AUC 0.95 [95%CI 0.90-0.98]) than IgG4 titre (AUC 0.87 [95%CI 0.79-0.94]). When inflammatory bowel disease (IBD) was excluded as a comorbid condition (IgG4-SC n = 20, PSC n = 22), the diagnostic AUC increased to 1.0, suggesting that the metabolome differences identified are not a result of the increased prevalence of IBD in PSC relative to IgG4-SC patients. Serum lactate (p < .0001), glucose (p < .01) and glutamine (p < .01) metabolites were increased in IgG4-related disease (IgG4-RD) and IgG4-SC individuals compared to PSC, whereas mobile choline (p < .05), 3-hydroxybutyric acid (p < .01) and -CH3 lipoprotein resonances (p < .01) were decreased. CONCLUSIONS: Taken together, serum metabolomic profiling has the potential to be incorporated as a diagnostic criterion, independent of IgG4 titre, to improve the diagnosis of IgG4-RD and help distinguish IgG4-SC from PSC.

Detection of Helicobacter pylori and its virulence genes (cagA, dupA, and vacA) among patients with gastroduodenal diseases in Chris Hani Baragwanath Academic Hospital, South Africa.

BACKGROUND: The global prevalence of H. pylori approaches 50%, with prevalence rates between 20 and 40% in developed countries and up to 90% in Africa and other developing nations of the world. Development of H. pylori-associated diseases is determined by a number of virulence factors. This study aimed at determining the prevalence of H. pylori infections and virulence genes (cagA, dupA, and vacA); the relationship between virulence factors and gastroduodenal diseases among patients. METHODS: Gastric biopsies were obtained from patients and cultured, DNA was extracted from cultured isolates and biopsies for PCR assay after which samples were investigated using standard laboratory procedures. Data of associated risk factors were obtained with the aid of questionnaires. RESULTS: Of the 444 participants, H. pylori was detected in 115 (25.9%) from culture analysis and 217 (48.9%) by direct PCR method. Ninety-eight (85.2%) of the culture-positive patients were also detected by PCR giving an overall prevalence of 52.7% (234/444). The highest number of H. pylori isolates 76.9% (180/234) was obtained from patients suffering from pangastritis. The CagA virulence gene was found in 62% (145/234), dupA in 53.4% (125/234) and vacA in 90.6% (212/234). VacA genotype s1 m1 was the most prevalent [56.4% (132)] followed by s2 m2 [11.5% (27)], s2 m1 [10.3% (24)] and [s1 m2 9.4% (22)]. There was a significant association observed in vacA s1 and peptic ulcer disease, as well as vacA s1/m2 and gastric erosion (P < 0.05). CONCLUSION: The study revealed a significant association between virulence genes and the development of certain forms of gastric infections while the variations in H. pylori detection and the associated risk factors investigated in the study were not significantly related.