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Best Practice & Research. Clinical Gastroenterology

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https://www.readbyqxmd.com/read/30343715/risk-stratification-and-prognostic-modelling-in-primary-biliary-cholangitis
#1
REVIEW
Jorn C Goet, Maren H Harms, Marco Carbone, Bettina E Hansen
Primary biliary cholangitis (PBC) is a slowly progressive chronic cholestatic liver disease that, in a subgroup of patients, may result in liver failure or death. The definition of specific risk profiles, i.e. risk stratification, is of critical importance for the identification of these subgroups and thereby the targeting of care. Over the last few years large multicentre cohort studies have improved our knowledge regarding factors associated with progressive disease. Stratification based on biochemical response to ursodoxycholic acid provides a readily available measure to identify groups that might benefit from additional therapies to further improve prognosis...
June 2018: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/30343714/improving-prognosis-in-primary-biliary-cholangitis-therapeutic-options-and-strategy
#2
REVIEW
Maren H Harms, Henk R van Buuren, Adriaan J van der Meer
Overall survival in primary biliary cholangitis is diminished. As patients are often asymptomatic, the disease may silently progress towards cirrhosis and liver failure. Timely diagnosis and effective treatment options are of vital importance to improve the prognosis of affected patients. Ursodeoxycholic acid is the standard of care first-line therapy and is associated with a reduced risk of liver transplantation and death. Treatment with UDCA is relevant for all patients, irrespective of disease stage or biochemical response...
June 2018: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/30343713/patterns-of-disease-progression-and-incidence-of-complications-in-primary-biliary-cholangitis-pbc
#3
REVIEW
Ashnila Janmohamed, Palak J Trivedi
Clinical outcome for patients with primary biliary cholangitis (PBC) is dictated by development of cirrhosis, portal hypertension and its associated complications; including for some, a predisposition toward hepatocellular carcinoma. However rates of clinical progression vary, and accurately identifying disease course is of critical importance to patients, clinicians, as well as industry, who are committed to developing new effective and life-prolonging therapy as well as treating symptoms that appear disproportionate to underlying disease severity...
June 2018: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/30343712/primary-biliary-cholangitis-and-bone-disease
#4
REVIEW
Albert Parés, Núria Guañabens
Osteoporosis, characterized by compromised bone strength leading to fragility fractures, is a common event in patients with primary biliary cholangitis (PBC). Osteomalacia, defined by poor bone mineralization is very uncommon. The pathogenesis of osteoporosis is not well clarified, but it mainly results from low bone formation. Few reports have revealed increased bone resorption, particularly in end-stage disease. The prevalence of osteoporosis is about 35% in the most significant studies, and it depends on the diagnostic criteria and severity of liver damage...
June 2018: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/30343711/variant-syndromes-of-primary-biliary-cholangitis
#5
REVIEW
Lisa Schulz, Marcial Sebode, Sören A Weidemann, Ansgar W Lohse
Patients with primary biliary cholangitis (PBC) can show biochemical, serological and/or histological features of autoimmune hepatitis (AIH). The term 'AIH-PBC overlap syndrome' has been used frequently for these cases and implies the coexistence of two separate diseases. However, the boundaries between 'classical' PBC, PBC with features of AIH and 'classical' AIH are difficult to define, and therefore the term 'variant syndrome' should be preferred. A variant syndrome must primarily be assumed in PBC patients showing pronounced hepatitic activity, either expressed by elevated transaminases and raised levels of serum IgG/gammaglobulins or more specifically by liver biopsy showing a modified hepatitis activity index (mHAI) score of >4/18...
June 2018: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/30343710/pbc-and-related-extrahepatic-diseases
#6
REVIEW
Annarosa Floreani, Nora Cazzagon
Patients with PBC have at least 60% of probability to have an autoimmune extrahepatic condition. The pathogenesis of these conditions includes a common mechanism involving both innate and adaptive immune responses targeting cholangiocytes and different extrahepatic tissues. The recent EASL guidelines recommend the management of these conditions, although detailed practical treatments have not been indicated. Autoimmune extrahepatic conditions may include: rheumatologic, endocrine, pulmonary, gastrointestinal, dermatologic diseases...
June 2018: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/30343709/symptoms-of-pbc-pathophysiology-and-management
#7
REVIEW
Amardeep Khanna, Jess Leighton, Lin Lee Wong, David E Jones
Primary biliary cholangitis is a chronic cholestatic liver disease characterised by progressive bile duct damage and, ultimately, biliary cirrhosis. Though up to fifty percent of the patients can be asymptomatic at presentation, symptoms when present are frequently debilitating with significant impact on quality of life and functional status. Characteristic symptoms include pruritus, fatigue and an increasingly recognised mild cognitive impairment. With the exception of pruritus, the "classic" cholestatic symptom, therapeutic options to treat PBC related symptoms are currently limited leaving patients with often significant residual problems...
June 2018: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/30343708/evolution-of-our-understanding-of-pbc
#8
REVIEW
Atsushi Tanaka, Patrick S C Leung, M Eric Gershwin
The discovery of mitochondrial autoantigens recognized by antimitochondrial antibodies (AMAs) in 1987 marked the dawn of a new era in primary biliary cholangitis (PBC) research. Since then, there has been substantial progress in our understanding of PBC partly bestowed by the development of innovative technologies in molecular biology, immunology, and genetics. Here, we review this evolutionary progress in understanding PBC. We now recognize that the epitopes of AMAs, CD4+ , and CD8+ T cells are all mapped to the same region of the inner lipoyl domain of pyruvate dehydrogenase complex E2 subunit (PDC-E2), and that intrahepatic biliary epithelial cells (BECs) are exclusively targeted in PBC...
June 2018: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/30343707/is-pbc-a-viral-infectious-disease
#9
REVIEW
Andrew L Mason
The human betaretrovirus and the closely related mouse mammary tumor virus have been linked with the development of cholangitis and mitochondrial antibody production in patients with primary biliary cholangitis (PBC) and mouse models of autoimmune biliary disease, respectively. In vitro, betaretroviruses have been found to stimulate the expression of mitochondrial autoantigens on the cell surface of biliary epithelial cells. In vivo, both mitochondrial autoantigens and viral proteins have been shown to be co-expressed in biliary epithelium and lymphoid tissue...
June 2018: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/30343706/pathophysiology-of-primary-biliary-cholangitis
#10
REVIEW
Aliya F Gulamhusein, Gideon M Hirschfield
Primary biliary cholangitis is a prototypical autoimmune disease characterized by an overwhelming female predominance, a distinct clinical phenotype, and disease specific anti-mitochondrial antibodies targeted against a well-defined auto-antigen. In a genetically susceptible host, multi-lineage loss of tolerance to the E2 component of the 2-oxo-dehydrogenase pathway and dysregulated immune pathways directed at biliary epithelial cells leads to cholestasis, progressive biliary fibrosis, and cirrhosis in a subset of patients...
June 2018: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/30343705/geoepidemiology-and-epi-genetics-in-primary-biliary-cholangitis
#11
REVIEW
Rosa Roberto, Cristoferi Laura, Tanaka Atsushi, Invernizzi Pietro
Primary biliary cholangitis (PBC) is a rare female preponderant chronic autoimmune cholestatic liver disease, characterized by intrahepatic ductopenia and progressive fibrosis. During last decades incidence and prevalence showed an increasing rate which vary widely worldwide demonstrating an important interaction between environmental and genetic factors. Heritability suggested by familial occurrence and monozygotic twins concordance have been confirmed in more studies. Epigenetics mechanisms such as histone modification and DNA methylation can partially explain predisposition and inheritance of this disease...
June 2018: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/30343704/pbc-transplantation-and-disease-recurrence
#12
REVIEW
Frederik Nevens
Despite near universal use of ursodeoxycholic acid (UDCA) several patients with PBC still progress to liver transplant (LT) or death. Pruritus and fatigue are the most common symptoms. Liver transplantation for pruritus is highly effective but fatigue will not disappear in the majority of the patients. In contrast to other liver diseases, portal hypertension may develop in pre-cirrhotic patients with PBC. Patients with PBC have an incidence rate of 3.4 hepatocellular carcinoma cases for every 1000 patient-years and risk factors are advanced stage of the disease and male sex...
June 2018: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/30343703/preface-primary-biliary-cholangitis
#13
EDITORIAL
Henk R van Buuren, Bettina E Hansen
No abstract text is available yet for this article.
June 2018: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/30060945/can-il-23-be-a-good-target-for-ulcerative-colitis
#14
REVIEW
Mariangela Allocca, Federica Furfaro, Gionata Fiorino, Daniela Gilardi, Silvia D'Alessio, Silvio Danese
A considerable percentage of patients with ulcerative colitis (UC) do not respond to therapies, including anti-tumor necrosis factor (TNF) drugs and vedolizumab, or lose response over time. Hence the continuing need to find new therapeutic strategies and novel drugs to control this chronic debilitating disease. Increased levels of interleukin (IL)-23 and T helper (Th) 17 cell cytokines have been found in intestinal mucosa, plasma, and serum of patients with inflammatory bowel disease (IBD). IL23-blocking has been shown to reduce the severity of inflammation in experimental colitis...
February 2018: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/30060944/can-we-move-directly-from-5-asa-to-a-biologic-agent-in-ulcerative-colitis
#15
REVIEW
Pieter Hindryckx, Gregor Novak
European consensus guidelines and reimbursement policies position biologic drugs for ulcerative colitis (UC) as a third-line treatment, after failure of 5-aminosalicylic acid (5-ASA) and corticosteroids/thiopurines. While 5-ASA have a very favorable safety profile, (prolonged) use of corticosteroids and thiopurines is associated with potentially serious adverse events. The therapeutic landscape of UC is rapidly evolving and selective biologic drugs with improved safety are being introduced. The first biosimilars have entered the market, leading to improved cost-effectiveness of older biologic drugs...
February 2018: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/30060943/jak-inhibitors-novel-developments-in-management-of-ulcerative-colitis
#16
REVIEW
Gionata Fiorino, Ferdinando D'Amico, Angelo Italia, Daniela Gilardi, Federica Furfaro, Silvio Danese
Janus kinase inhibitors are small molecules, orally administered, under development for the treatment of ulcerative colitis. These molecules reduce the immune response, blocking the signal transduction of multiple cytokines implicated in the activation of inflammation. Currently multiple JAK inhibitors are being evaluated in clinical trials. The aim of this review is to examine the efficacy and the safety of the JAK inhibitors being tested and to discuss the available data on the use of these drugs in moderate-to-severe ulcerative colitis, in order to understand how these new molecules can fit into the therapeutic algorithm of patients with ulcerative colitis...
February 2018: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/30060942/the-impact-of-biologics-in-surgical-outcomes-in-ulcerative-colitis
#17
REVIEW
Marjorie C Argollo, Paulo Gustavo Kotze, Antonino Spinelli, Tarcia N F Gomes, Silvio Danese
Ulcerative Colitis (UC) is an immune mediated condition characterized by inflammation of colonic mucosa, associated with progressive damage of the colon and possible complications, such as hemorrhage, perforation and cancer. It is strongly advocated a treat to target approach in patients with UC consisting in an early and aggressive inflammatory control. Some patients can require colectomy for medically refractory disease or to treat colonic neoplasia. Even though the first line biologic therapy targeting the tumor necrosis factor-alfa (TNF-α) is associated with improvement of the inflammation in some patients, others do not respond at first or lose response over time...
February 2018: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/30060941/surgery-in-ulcerative-colitis-when-how
#18
REVIEW
Gaetano Gallo, Paulo Gustavo Kotze, Antonino Spinelli
Ulcerative Colitis (UC) is an idiopathic chronically-remitting inflammatory bowel disorder characterized by a contiguous inflammation of the colonic mucosa affecting the rectum that generally extends proximally in a continuous manner through the entire colon. Patients typically experience intermittent exacerbations, with symptoms characterized by bloody diarrhea associated with urgency and tenesmus. The anatomical extent of mucosal involvement is the most important factor determining disease course and is an important predictor of colectomy...
February 2018: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/30060940/acute-severe-ulcerative-colitis-state-of-the-art-treatment
#19
REVIEW
Javier P Gisbert, María Chaparro
Acute severe ulcerative colitis (ASUC) is a potentially life-threatening condition. In the present review, we give a broad overview of the state of the art in the management of this condition. A systematic bibliographic search was performed in PubMed. Patient with ASUC should be hospitalized and managed by a multidisciplinary team (gastroenterologist plus surgeon). Intravenous corticosteroids remain the cornerstone of medical therapy. However, about 30% of patients do not respond. After failing 3-5 days of corticosteroids, patients should be considered for either rescue medical therapy or for colectomy...
February 2018: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/30060939/the-treatment-of-refractory-ulcerative-colitis
#20
REVIEW
Guillaume Pineton de Chambrun, Barbara Tassy, Laura Kollen, Gaspard Dufour, Jean-Christophe Valats, Michael Bismuth, Natalie Funakoshi, Fabrizio Panaro, Pierre Blanc
Ulcerative proctitis is defined as a mucosal inflammation limited to the rectum. Ulcerative proctitis is responsible for distressing symptoms and alteration of patient quality of life. Effective treatment is important to prevent or delay proximal extension of the disease and to improve quality of life. Refractory ulcerative proctitis is defined as the failure of topical and oral 5-aminosalicylic acid and corticosteroids. Medical management of refractory ulcerative proctitis may be challenging as there is little evidence regarding drug efficacy in this clinical situation...
February 2018: Best Practice & Research. Clinical Gastroenterology
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