Primary biliary cirrhosis Carey, Elizabeth J, MD; Ali, Ahmad H, MD; Lindor, Keith D, MD
The Lancet (British edition),
10/2015, Letnik:
386, Številka:
10003
Journal Article
Recenzirano
Summary Primary biliary cirrhosis is a chronic cholestatic liver disease characterised by destruction of small intrahepatic bile ducts, leading to fibrosis and potential cirrhosis through resulting ...complications. The serological hallmark of primary biliary cirrhosis is the antimitochondrial antibody, a highly disease-specific antibody identified in about 95% of patients with primary biliary cirrhosis. These patients usually have fatigue and pruritus, both of which occur independently of disease severity. The typical course of primary biliary cirrhosis has changed substantially with the introduöction of ursodeoxycholic acid (UDCA). Several randomised placebo-controlled studies have shown that UDCA improves transplant-free survival in primary biliary cirrhosis. However, about 40% of patients do not have a biochemical response to UDCA and would benefit from new therapies. Liver transplantation is a life-saving surgery with excellent outcomes for those with decompensated cirrhosis. Meanwhile, research on nuclear receptor hormones has led to the development of exciting new potential treatments. This Seminar will review the current understanding of the epidemiology, pathogenesis, and natural history of primary biliary cirrhosis, discuss management of the disease and its sequelae, and introduce research on new therapeutic options.
Primary sclerosing cholangitis Hirschfield, Gideon M, Dr; Karlsen, Tom H, Prof; Lindor, Keith D, Prof ...
The Lancet (British edition),
11/2013, Letnik:
382, Številka:
9904
Journal Article
Recenzirano
Summary Primary sclerosing cholangitis is the classic hepatobiliary manifestation of inflammatory bowel disease and is generally chronic and progressive. Patients frequently present with ...asymptomatic, anicteric cholestasis, but many develop progressive biliary strictures with time, leading to recurrent cholangitis, biliary cirrhosis, and end-stage liver disease. Medical treatment does not slow the progression of disease, and many patients need liver transplantation, after which recurrent disease is a risk. The increased incidence of hepatobiliary cancer, which is not related to the underlying severity of biliary fibrosis, is of particular concern. Risk of colorectal cancer is also increased in patients with coexistent inflammatory bowel disease. Mechanistic insights have arisen from studies of secondary sclerosing cholangitis, in which a similar clinical profile is associated with a specific cause, and genomic studies have elucidated potential disease-initiating pathways in the primary form. The close association between inflammatory bowel disease and primary sclerosing cholangitis underscores the need to further understand the role of environmental factors in generation of lymphocytes that are postulated to be retargeted, deleteriously, to the biliary tree. Treatment of primary sclerosing cholangitis is confined to supportive measures, but advances in pathobiology suggest that new stratified approaches will soon be available.
Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by progressive fibroinflammatory destruction of the intra- and/or extrahepatic biliary ducts. While its features ...and disease course can be variable, most patients with PSC have concurrent inflammatory bowel disease and will eventually develop liver cirrhosis and end-stage liver disease, with liver transplantation representing the only potentially curative option. Importantly, PSC is associated with a significantly increased risk of malignancy compared to the general population, mainly cholangiocarcinoma, gallbladder carcinoma, hepatocellular carcinoma, and colorectal cancer, with nearly 50% of deaths in patients with PSC being due to cancer. Therefore, robust surveillance strategies are needed, though uncertainty remains regarding how to best do so. In this review, we discuss the epidemiology, prevention, and surveillance of cancers in patients with PSC. Where evidence is limited, we present pragmatic approaches based on currently available data and expert opinion.
Because those selected for leadership in academic medicine often have a record of academic productivity, publication disparities may help explain the gender imbalance in leadership roles. The authors ...aimed to compare the publication records, academic promotions, and leadership appointments of women and men physicians longitudinally throughout academic careers.
In 2007, the authors conducted a retrospective, longitudinal cohort study of all 25 women physicians then employed at Mayo Clinic with ≥20 years of service at Mayo and of 50 male physician controls, matched 2:1 by appointment date and career category, to women. The authors recorded peer-reviewed publications, timing of promotion, and leadership appointments throughout their careers.
Women published fewer articles throughout their careers than men (mean standard deviation 29.5 28.8 versus 75.8 60.3, P = .001). However, after 27 years, women produced a mean of 1.57 more publications annually than men (P < .001). Thirty-three men (66%) achieved an academic rank of professor compared with seven women (28%) (P = .01). Throughout their careers, women held fewer leadership roles than men (P < .001). Nearly half (no. = 11; 44%) of women attained no leadership position, compared with 15 men (30%).
Women's publication rates increase and actually exceed those of men in the latter stages of careers, yet women hold fewer leadership positions than men overall, suggesting that academic productivity assessed midcareer may not be an appropriate measure of leadership skills and that factors other than publication record and academic rank should be considered in selecting leaders.
Primary sclerosing cholangitis is a chronic cholestatic liver disease that can shorten life and may require liver transplantation. The cause is unknown, although it is commonly associated with ...colitis. There is no approved or proven therapy, although ursodeoxycholic acid is used by many on an empiric basis. Complications including portal hypertension, fat-soluble vitamin deficiency, metabolic bone diseases, and development of cancers of the bile duct or colon can occur.
Primary sclerosing cholangitis (PSC) is a chronic fibroinflammatory syndrome involving the biliary tract, often accompanied by inflammatory bowel disease (IBD). This syndrome is a prototype disease ...linking chronic inflammation to carcinogenesis. Indeed, PSC is associated with an increased risk of cholangiocarcinoma (CCA), gallbladder cancer, hepatocellular carcinoma (HCC), and colorectal cancer. Herein, we review the risk for these malignancies in PSC and discuss rational cancer surveillance strategies for these patients. Where evidence is limited, we suggest a pragmatic approach. In this regard, we recommend interval screening for CCA with noninvasive imaging modalities and serum carbohydrate antigen 19‐9 determinations annually. These imaging studies also serve to screen for gallbladder cancer and HCC. Screening for colorectal cancer is more firmly established in PSC patients with IBD and includes colonoscopy at the time of PSC diagnosis and, thereafter, at 1‐2‐year intervals. We also highlight areas where more information is required, such as management of biliary tract dysplasia and cancer chemoprevention in PSC. (HEPATOLOGY 2011)
Primary sclerosing cholangitis (PSC), first described in the mid-1850s, is a complex liver disease that is heterogeneous in its presentation. PSC is characterized by chronic cholestasis associated ...with chronic inflammation of the biliary epithelium, resulting in multifocal bile duct strictures that can affect the entire biliary tree. Chronic inflammation leads to fibrosis involving the hepatic parenchyma and biliary tree, which can lead to cirrhosis and malignancy. The etiology of PSC is not fully understood, which in part explains the lack of effective medical therapy for this condition. However, we have begun to better understand the molecular pathogenesis of PSC. The recognition of specific clinical subtypes and their pattern of progression could improve phenotypic and genotypic classification of the disease. We review our current understanding of this enigmatic disorder and discuss important topics for future studies.
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