scholarly journals The Role of Genetic and Immune Factors for the Pathogenesis of Primary Sclerosing Cholangitis in Childhood

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Priscila Menezes Ferri ◽  
Ana Cristina Simões e Silva ◽  
Soraya Luiza Campos Silva ◽  
Diego Junior Queiroga de Aquino ◽  
Eleonora Druve Tavares Fagundes ◽  
...  
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Clinical Laboratory ◽  
Pediatric Population ◽  
Young Patients ◽  
Cholestatic Liver Disease ◽  
Gamma Glutamyl Transferase ◽  
Immune System Activation ◽  
Glutamyl Transferase

Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by chronic inflammation of the biliary tree resulting in liver fibrosis. PSC is more common in male less than 40 years of age. The diagnosis of PSC is based on clinical, laboratory, image, and histological findings. A biochemical profile of mild to severe chronic cholestasis can be observed. Endoscopic retrograde cholangiography is the golden standard method for diagnosis, but magnetic resonance cholangiography is currently also considered a first-line method of investigation. Differences in clinical and laboratory findings were observed in young patients, including higher incidence of overlap syndromes, mostly with autoimmune hepatitis, higher serum levels of aminotransferases and gamma-glutamyl transferase, and lower incidence of serious complications as cholangiocarcinoma. In spite of the detection of several HLA variants as associated factors in large multicenter cohorts of adult patients, the exact role and pathways of these susceptibility genes remain to be determined in pediatric population. In addition, the literature supports a role for an altered immune response to pathogens in the pathogenesis of PSC. This phenomenon contributes to abnormal immune system activation and perpetuation of the inflammatory process. In this article, we review the role of immune and genetic factors in the pathogenesis of PSC in pediatric patients.

scholarly journals Role of the Microbiota and Antibiotics in Primary Sclerosing Cholangitis

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
James H. Tabibian ◽  
Jayant A. Talwalkar ◽  
Keith D. Lindor
Keyword(s):  
Inflammatory Bowel Disease ◽  
Liver Disease ◽  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Clinical Evidence ◽  
Cholestatic Liver Disease ◽  
Concise Review ◽  
Inflammatory Bowel ◽  
Considerable Morbidity

Primary sclerosing cholangitis (PSC) is an idiopathic, progressive, cholestatic liver disease with considerable morbidity and mortality and no established pharmacotherapy. In addition to the long-recognized association between PSC and inflammatory bowel disease, several lines of preclinical and clinical evidence implicate the microbiota in the etiopathogenesis of PSC. Here we provide a concise review of these data which, taken together, support further investigation of the role of the microbiota and antibiotics in PSC as potential avenues toward elucidating safe and effective pharmacotherapy for patients afflicted by this illness.

scholarly journals Gut Microbiome of Children and Adolescents With Primary Sclerosing Cholangitis in Association With Ulcerative Colitis

2021 ◽  
Vol 11 ◽  
Author(s):  
Ramon V. Cortez ◽  
Luana N. Moreira ◽  
Marina Padilha ◽  
Mariana D. Bibas ◽  
Ricardo K. Toma ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Pediatric Patients ◽  
Total Bilirubin ◽  
Intestinal Microbiome ◽  
Gamma Glutamyl Transferase ◽  
Microbiome Composition ◽  
Gamma Glutamyl ◽  
Glutamyl Transferase

Few studies reported the relation of intestinal microbiome composition and diversity in pediatric patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). In this cross-sectional study, we selected patients younger than 19 years old from the pediatric gastroenterology and hepatology outpatient clinic of a tertiary hospital to describe the intestinal microbiome of pediatric patients with PSC associated or not to UC. Patients were divided in PSC, PSC+UC, and UC diagnosis. A stool sample was collected from each patient (n=30) and from a healthy relative/neighbor (n=23). The microbiome composition was assessed using MiSeq (Illumina) platform. Differences in microbial composition were found between PSC and PSC+UC groups. The relative abundance of Veillonella and Megasphaera genera were increased depending on patients’ age at diagnosis. Veillonella was also increased in patients who were in an active status of the disease. Both genera were positively correlated to total bilirubin and gamma-glutamyl transferase. As a conclusion, the disease, the age and the disease activity status seem to influence the intestinal microbiome, highlighting the difference of intestinal microbiome profile for patients depending on age at diagnosis. We also showed an increase of Veillonella in patients with PSC and PSC+UC, and a positive correlation of dysbiosis and higher gamma-glutamyl transferase and total bilirubin in PSC+UC patients. Our findings are promising in the diagnosis, prognosis, and future therapeutic perspectives for PSC patients.

The Role of IFNγ in the Immune Pathogenesis of Primary Sclerosing Cholangitis

2018 ◽  
Vol 56 (01) ◽  
pp. E2-E89
Author(s):  
G Ravichandran ◽  
T Krech ◽  
G Tiegs ◽  
R Barikbin
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Immune Pathogenesis

scholarly journals The Role of Microbiota in Primary Sclerosing Cholangitis and Related Biliary Malignancies

2021 ◽  
Vol 22 (13) ◽  
pp. 6975
Author(s):  
Burcin Özdirik ◽  
Tobias Müller ◽  
Alexander Wree ◽  
Frank Tacke ◽  
Michael Sigal
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Gut Microbiome ◽  
Sclerosing Cholangitis ◽  
Functional Characterization ◽  
Significant Risk ◽  
Pharmacological Agents ◽  
Experimental Mouse ◽  
Biliary Malignancies ◽  
End Stage

Primary sclerosing cholangitis (PSC) is an immune-related cholangiopathy characterized by biliary inflammation, cholestasis, and multifocal bile duct strictures. It is associated with high rates of progression to end-stage liver disease as well as a significant risk of cholangiocarcinoma (CCA), gallbladder cancer, and colorectal carcinoma. Currently, no effective medical treatment with an impact on the overall survival is available, and liver transplantation is the only curative treatment option. Emerging evidence indicates that gut microbiota is associated with disease pathogenesis. Several studies analyzing fecal and mucosal samples demonstrate a distinct gut microbiome in individuals with PSC compared to healthy controls and individuals with inflammatory bowel disease (IBD) without PSC. Experimental mouse and observational human data suggest that a diverse set of microbial functions may be relevant, including microbial metabolites and bacterial processing of pharmacological agents, bile acids, or dietary compounds, altogether driving the intrahepatic inflammation. Despite critical progress in this field over the past years, further functional characterization of the role of the microbiota in PSC and related malignancies is needed. In this review, we discuss the available data on the role of the gut microbiome and elucidate important insights into underlying pathogenic mechanisms and possible microbe-altering interventions.

Ammonia metabolism

1978 ◽  
Vol 235 (4) ◽  
pp. F265-F277 ◽  
Author(s):  
R. L. Tannen
Keyword(s):  
Critical Role ◽  
Tca Cycle ◽  
Gamma Glutamyl Transferase ◽  
Urine Ph ◽  
Ammonia Metabolism ◽  
Adaptive Process ◽  
Purine Nucleotide Cycle ◽  
Tca Cycle Intermediates ◽  
Glutamyl Transferase

The pathways responsible for an the mechanisms underlying the adaptive increase in ammonia production in response to acidosis are considered. It seems unlikely that the cytosolic pathways (glutamine synthetase, glutaminase II, phosphate-independent glutaminase, and gamma-glutamyl transferase) are of primary importance in the adaptive process, but the role of the purine nucleotide cycle has not been resolved. The intramitochondrially located phosphate-dependent glutaminase pathway is generally believed to be of primary importance. Adaptation involved either enhanced glutamine entry into the mitrochondria and/or activation of phosphate-dependent glutaminase, but the relative importance of each has not been resolved definitively. The overall adaptive response is probably modulated by factors regulating alpha-ketoglutarate metabolism to phosphoenolpyruvate, and possibly also by metabolism of TCA cycle intermediates. It seems unlikely that a decrease in systemic pH is the direct effector for the acidosis-induced increase in ammonia formation; however, the resulting decrease in urine pH may play a critical role. Other potential messengers, including potassium, glucocorticoids, mineralocorticoids, cyclic AMP, and calcium probably do not serve a primary function, but the importance of other circulating factor(s) is unclear.

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