scholarly journals Primary Sclerosing Cholangitis: Therapeutic Options and Surveillance Management

2016 ◽  
Vol 9 ◽  
pp. CGast.S38451 ◽  
Author(s):  
Aditi Kumar ◽  
Daniel Wheatley ◽  
Amar Puttanna
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Disease Recurrence ◽  
Evidence Base ◽  
Therapeutic Options ◽  
Weak Evidence ◽  
Immune Mediated ◽  
Metabolic Bone ◽  
Bowel Disorders ◽  
Risk Of Disease

Primary sclerosing cholangitis is a chronic immune-mediated liver disease. Though rare, it poses several clinical concerns for the managing physician. There are currently limited therapeutic options in the management of the condition and weak evidence base behind them. Endoscopic intervention is limited to those patients with obstructing stricture-related disease, and even liver transplantation has a risk of disease recurrence. Surveillance for inflammatory bowel disorders, metabolic bone disease, and malignancy is paramount when managing such patients. This article provides an overview of the condition with further focus on current therapeutic options and guidance on surveillance management.

Cholestatic Liver Injury: Care of Patients With Primary Biliary Cholangitis or Primary Sclerosing Cholangitis

2016 ◽  
Vol 27 (4) ◽  
pp. 441-452 ◽  
Author(s):  
Laurie Larson ◽  
Michelle James ◽  
Andrea Gossard
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Disease Recurrence ◽  
Outpatient Setting ◽  
Primary Biliary Cholangitis ◽  
Malignant Neoplasms ◽  
Cholestatic Liver Disease ◽  
Gallbladder Polyps ◽  
Increased Risk ◽  
Common Causes

The most common causes of chronic cholestatic liver disease are primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Both disease processes are characterized by a destruction of intrahepatic and/or extrahepatic biliary ducts. The etiology is not entirely clear; however, there is an underlying autoimmune component contributing to both disease processes. Although PBC and PSC are often diagnosed and managed in the outpatient setting, in some instances, a patient may have jaundice, fatigue, and pruritus requiring evaluation and determination of the cholestatic cause. Patients with PSC should be monitored for evidence of cholangiocarcinoma, colon cancer, and gallbladder polyps as they are at an increased risk of malignant neoplasms. Liver transplant has the potential for improving quality of life, although disease recurrence is a risk.

scholarly journals Primary sclerosing cholangitis

2008 ◽  
Vol 22 (8) ◽  
pp. 689-698 ◽  
Author(s):  
Marina G Silveira ◽  
Keith D Lindor
Keyword(s):  
Liver Disease ◽  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Serum Alkaline Phosphatase ◽  
Cholestatic Liver Disease ◽  
Biliary Strictures ◽  
Vitamin Deficiencies ◽  
Metabolic Bone ◽  
High Doses ◽  
End Stage

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the bile ducts, resulting in end-stage liver disease and reduced life expectancy. PSC primarily affects young and middle-aged men, often in association with underlying inflammatory bowel disease. The etiology of PSC includes immune-mediated components and elements of undefined nature. A cholestatic picture of liver biochemistries with elevations in serum alkaline phosphatase, nonspecific autoantibodies such as perinuclear antineutrophilic antibody, antinuclear antibodies and smooth muscle antibodies, and diffuse multifocal biliary strictures, resulting in a ‘beaded’ appearance on radiographic studies, are the hallmarks of the disease. No effective medical therapy is currently available, although clinical studies are in progress. Ursodeoxycholic acid at high doses (28 mg/kg/day to 30 mg/kg/day) is the most promising agent but is unproven so far. Liver transplantation is currently the only life-extending therapy for patients with end-stage disease, although recurrent disease can be observed in the transplanted liver. The multiple complications of PSC include pruritus, fatigue, vitamin deficiencies, metabolic bone disease, peristomal varices, bacterial cholangitis, dominant biliary strictures, gallbladder stones and polyps, and malignancy, particularly cholangiocarcinoma, which is the most lethal complication of PSC.

scholarly journals Administration of Human MSC-Derived Extracellular Vesicles for the Treatment of Primary Sclerosing Cholangitis: Preclinical Data in MDR2 Knockout Mice

2020 ◽  
Vol 21 (22) ◽  
pp. 8874
Author(s):  
Roberta Angioni ◽  
Bianca Calì ◽  
Vasanthy Vigneswara ◽  
Marika Crescenzi ◽  
Ana Merino ◽  
...  
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Extracellular Vesicles ◽  
Sclerosing Cholangitis ◽  
Serum Levels ◽  
Portal Triad ◽  
Immune Mediated ◽  
Nfkb Activation ◽  
Effective Therapeutic Strategy ◽  
Progressive Liver Disease ◽  
Clinical Experiments

Primary Sclerosing Cholangitis (PSC) is a progressive liver disease for which there is no effective medical therapy. PSC belongs to the family of immune-mediated biliary disorders and it is characterized by persistent biliary inflammation and fibrosis. Here, we explored the possibility of using extracellular vesicles (EVs) derived from human, bone marrow mesenchymal stromal cells (MSCs) to target liver inflammation and reduce fibrosis in a mouse model of PSC. Five-week-old male FVB.129P2-Abcb4tm1Bor mice were intraperitoneally injected with either 100 µL of EVs (± 9.1 × 109 particles/mL) or PBS, once a week, for three consecutive weeks. One week after the last injection, mice were sacrificed and liver and blood collected for flow cytometry analysis and transaminase quantification. In FVB.129P2-Abcb4tm1Bor mice, EV administration resulted in reduced serum levels of alkaline phosphatase (ALP), bile acid (BA), and alanine aminotransferase (ALT), as well as in decreased liver fibrosis. Mechanistically, we observed that EVs reduce liver accumulation of both granulocytes and T cells and dampen VCAM-1 expression. Further analysis revealed that the therapeutic effect of EVs is accompanied by the inhibition of NFkB activation in proximity of the portal triad. Our pre-clinical experiments suggest that EVs isolated from MSCs may represent an effective therapeutic strategy to treat patients suffering from PSC.

Immune-mediated diseases in primary sclerosing cholangitis

2011 ◽  
Vol 43 (10) ◽  
pp. 802-806 ◽  
Author(s):  
Laetitia E. Lamberts ◽  
Marcel Janse ◽  
Elizabeth B. Haagsma ◽  
Arie P. van den Berg ◽  
Rinse K. Weersma
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Immune Mediated

Therapy of Primary Sclerosing Cholangitis - Today and Tomorrow

2015 ◽  
Vol 33 (Suppl. 2) ◽  
pp. 149-163 ◽  
Author(s):  
Emina Halilbasic ◽  
Claudia Fuchs ◽  
Harald Hofer ◽  
Gustav Paumgartner ◽  
Michael Trauner
Keyword(s):  
Bile Acid ◽  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Farnesoid X Receptor ◽  
Therapeutic Options ◽  
Current Status ◽  
Peroxisome Proliferator ◽  
Hepatocellular Injury ◽  
Close Link ◽  
Acid Receptor

Primary sclerosing cholangitis (PSC) represents a fibro-obliterative bile duct disease with unpredictable individual clinical course that may progress to liver cirrhosis and malignancy. Due to our incomplete understanding of the etiology and pathogenesis of this disease, the therapeutic options are still rather limited. Bile acids play a key role in mediating cholangiocellular and hepatocellular injury in cholangiopathies such as PSC. Therefore, strategies targeting bile composition and homeostasis are valid approaches in PSC. Ursodeoxycholic acid (UDCA) is the paradigm therapeutic bile acid and its role in medical therapy of PSC is still under debate. Promising novel bile acid-based therapeutic options include 24-norursodeoxycholic acid (norUDCA), a side chain-shortened C23 homologue of UDCA, and bile acid receptor/farnesoid X receptor agonists (e.g. obeticholic acid). Other nuclear receptors such as fatty acid-activated peroxisome proliferator-activated receptors, vitamin D receptor and vitamin A receptors (retinoic acid receptor, retinoid X receptor) are also of potential interest and can be targeted by already available drugs. Furthermore, drugs targeting the gut-liver axis (e.g. intregrin blockers such as vedolizumab, antibiotics) appear promising, based on the close link of PSC to inflammatory bowel disease and the emerging relevance of the gut microbiome for the development of PSC. Finally, fibrosis represents a valid therapeutic target for anti-fibrotic drugs (e.g. simtuzumab) in PSC as paradigm fibro-obliterative disease. This review summarizes the current status and recent progress in the development of targeted therapeutic approaches based on increasing knowledge about the pathogenesis of this disease.

Primary sclerosing cholangitis

2010 ◽  
pp. 2468-2473
Author(s):  
R.W. Chapman ◽  
K.D. Williamson
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Weight Loss ◽  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Close Association ◽  
Biliary Tree ◽  
Cholestatic Liver Disease ◽  
Immune Mediated ◽  
Inflammatory Bowel

Case History—A 60 yr old woman, known to have long standing colitis, now presenting with abdominal pain and weight loss. Primary sclerosing cholangitis is a chronic cholestatic liver disease caused by diffuse inflammation and fibrosis that can involve the entire biliary tree. The cause is unknown, but presumed to be immune mediated, and there is a very close association with inflammatory bowel disease, particularly ulcerative colitis....

scholarly journals Gene Expression by PBMC in Primary Sclerosing Cholangitis: Evidence for Dysregulation of Immune Mediated Genes

2006 ◽  
Vol 13 (2-4) ◽  
pp. 265-271 ◽  
Author(s):  
Christopher A. Aoki ◽  
Kevin Dawson ◽  
Thomas P. Kenny ◽  
M. Eric Gershwin ◽  
Christopher L. Bowlus
Keyword(s):  
Gene Expression ◽  
Primary Sclerosing Cholangitis ◽  
Messenger Rna ◽  
Sclerosing Cholangitis ◽  
Mononuclear Cells ◽  
Differentially Expressed ◽  
Peripheral Blood Mononuclear ◽  
Immune Mediated ◽  
Membrane Spanning ◽  
Immune Related Genes

Primary sclerosing cholangitis (PSC) is a chronic disease of the bile ducts characterized by an inflammatory infiltrate and obliterative fibrosis. The precise role of the immune system in the pathogenesis of PSC remains unknown. We used RNA microarray analysis to identify immune-related genes and pathways that are differentially expressed in PSC. Messenger RNA (mRNA) from peripheral blood mononuclear cells (PBMC) was isolated from both patients with PSC and age and sex matched healthy controls. Samples from 5 PSC patients and 5 controls were analyzed by microarray and based upon rigorous statistical analysis of the data, relevant genes were chosen for confirmation by RT-PCR in 10 PSC patients and 10 controls. Using unsupervised hierarchical clustering, gene expression in PSC was statistically different from our control population. Interestingly, genes within the IL-2 receptor beta, IL-6 and MAP Kinase pathways were found to be differently expressed in patients with PSC compared to controls. Further, individual genes, TNF-α induced protein 6 (TNFaip6) and membrane-spanning 4-domains, subfamily A (ms4a) were found to be upregulated in PSC while similar to Mothers against decapentaplegic homolog 5 (SMAD 5) was downregulated. In conclusion, several immune-related pathways and genes were differentially expressed in PSC compared to control patients, giving further evidence that this disease is systemic and immune-mediated.

Timing, Management, and Outcomes of Liver Transplantation in Primary Sclerosing Cholangitis

2017 ◽  
Vol 37 (04) ◽  
pp. 305-313 ◽  
Author(s):  
Cynthia Levy ◽  
Eric Martin
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Primary Sclerosing Cholangitis ◽  
Graft Survival ◽  
Sclerosing Cholangitis ◽  
Cholestatic Liver Disease ◽  
Biliary Cirrhosis ◽  
Immune Mediated ◽  
End Stage ◽  
Patient And Graft Survival

AbstractPrimary sclerosing cholangitis (PSC) is a chronic, immune-mediated cholestatic liver disease that often progresses to secondary biliary cirrhosis and end-stage liver disease. Short of liver transplantation (LT), there is no effective treatment for PSC. PSC accounts for approximately 5% of total adult LTs in the US and is currently the fifth most common indication for LT. Patient and graft survival for PSC is among the highest for all indications for LT. The main factors that impact outcomes after LT for PSC include biliary strictures, rejection, and recurrence of PSC. Recurrent PSC (rPSC) develops in 20% of LT recipients within 5 years of LT and is associated with negative patient and graft survival. LT is a viable option for recipients who develop rPSC and progress to graft failure.

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