scholarly journals Changes in beta-catenin expression and activation during progression of primary sclerosing cholangitis predict disease recurrence

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Mary Ayers ◽  
Silvia Liu ◽  
Aatur D. Singhi ◽  
Karis Kosar ◽  
Pamela Cornuet ◽  
...  
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Bile Ducts ◽  
Statistical Significance ◽  
Disease Recurrence ◽  
Immunohistochemical Localization ◽  
Cholestatic Liver Disease ◽  
Beta Catenin ◽  
Biliary Injury ◽  
Pathology Reports

AbstractPrimary sclerosing cholangitis (PSC) is a rare, chronic, cholestatic liver disease characterized by progressive inflammation and fibrosis of the bile ducts. We have previously demonstrated the importance of Wnt/β-catenin signaling in mouse models of PSC. In this study, we wished to determine the clinical relevance of β-catenin localization in patient samples. In livers explanted from patients diagnosed with PSC, the majority (12/16; 75%) lacked β-catenin protein expression. Biopsies from patients post-transplant were classified as recurrent or non-recurrent based on pathology reports and then scored for β-catenin activation as a function of immunohistochemical localization. Despite lack of statistical significance, patients with recurrent primary disease (n = 11) had a greater percentage of samples with nuclear, transcriptionally active β-catenin (average 58.8%) than those with no recurrence (n = 10; 40.53%), while non-recurrence is correlated with β-catenin staining at the cell surface (average 52.63% for non-recurrent vs. 27.34% for recurrent), as determined by three different methods of analysis. β-catenin score and years-to-endpoint are both strongly associated with recurrence status (p = 0.017 and p = 0.00063, respectively). Finally, there was significant association between higher β-catenin score and increased alkaline phosphatase, a marker of biliary injury and disease progression. Thus, β-catenin expression and activation changes during the progression of PSC, and its localization may be a useful prognostic tool for predicting recurrence of this disease.

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 Management of primary sclerosing cholangitis and its complications: an algorithmic approach

2020 ◽  
Author(s):  
Michal Prokopič ◽  
Ulrich Beuers
Keyword(s):  
Liver Disease ◽  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Treatment Options ◽  
Diagnostic Procedures ◽  
Disease Recurrence ◽  
Cholestatic Liver Disease ◽  
Diagnostic Challenge ◽  
Algorithmic Approach ◽  
End Stage

AbstractPrimary sclerosing cholangitis (PSC) is a rare cholestatic liver disease, characterized by multiple strictures and dilatations of the intra- and extrahepatic bile ducts, leading to progressive liver fibrosis, in 10–15% cholangiocarcinoma, and ultimately end-stage liver disease. The pathogenesis is poorly understood, but (epi-)genetic factors, mechanisms of innate and adaptive immunity, toxic effects of hydrophobic bile acids, and possibly intestinal dysbiosis appear to be involved. The strong link with inflammatory bowel disease (IBD) is associated with a markedly enhanced risk of colorectal cancer which next to cholangiocarcinoma represents the most serious diagnostic challenge in long-term PSC management. Despite extensive research, no medical treatment has been proven so far to prolong the time to liver transplantation (LTx), which remains the effective treatment in late-stage disease. Recurrence of PSC after LTx is observed in up to 20% of patients. Here, we briefly summarize actual views on PSC pathogenesis and provide an algorithmic approach to diagnostic procedures and recommendations for the management of PSC and its complications. We describe promising treatment options subject to current clinical trials.

scholarly journals Magnetic Resonance Imaging in Primary Sclerosing Cholangitis

2021 ◽  
Vol 3 (2) ◽  
pp. 20-24
Author(s):  
Aldona Wybraniec-Zaręba ◽  
Julia Tuchalska-Czuroń ◽  
Gabriela Półtorak-Szymczak ◽  
Mariusz Furmanek ◽  
Jerzy Walecki ◽  
...  
Keyword(s):  
Bile Duct ◽  
Magnetic Resonance ◽  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Bile Ducts ◽  
Extrahepatic Bile Duct ◽  
Magnetic Resonance Cholangiopancreatography ◽  
Left Liver Lobe ◽  
Bile Duct Stenosis ◽  
Mri Features

Primary sclerosing cholangitis (PSC) is a chronic liver disease in which there are inflammation and scarring of the bile ducts leading to fibrosis, destruction and narrowing of the bile ducts, resulting in cholestasis. In the long run, PSC can cause liver cirrhosis and failure. In clinical practice, the diagnosis of PSC is generally based on blood tests and imaging studies (currently preferably magnetic resonance cholangiopancreatography). To make a diagnosis of PSC it is necessary to exclude secondary causes of sclerosing cholangitis. The most common MRI features of PSC concerning bile ducts are: bile duct dilatation, beading, extrahepatic bile duct stenosis, wall enhancement and thickening. The most common MRI features of PSC concerning hepatic parenchyma are: rounded shape of the liver caused by hypertrophy of caudate lobe and left liver lobe, atrophy of the right lobe, enlargement of portal and/or portacaval lymph nodes, peripheral parenchymal inflammation, wedge-shaped confluent fibrosis, heterogeneity of the liver parenchyma, periportal oedema, cirrhosis with indirect signs of portal hypertension such as splenomegaly, ascites and collateral vasculature.

scholarly journals Successful Treatment of Recurrent Primary Sclerosing Cholangitis after Orthotopic Liver Transplantation with Oral Vancomycin

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Yinka K. Davies ◽  
Cynthia J. Tsay ◽  
Dario V. Caccamo ◽  
Kathleen M. Cox ◽  
Ricardo O. Castillo ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Liver Transplantation ◽  
Primary Sclerosing Cholangitis ◽  
Orthotopic Liver Transplantation ◽  
Successful Treatment ◽  
Sclerosing Cholangitis ◽  
Bile Ducts ◽  
Biliary Tree ◽  
Oral Vancomycin ◽  
Inflammatory Bowel

Primary sclerosing cholangitis (PSC) is a progressive, cholestatic disease of the liver that is marked by inflammation of the bile ducts and damage to the hepatic biliary tree. Approximately 60–70% of patients also have inflammatory bowel disease and progression of PSC can lead to ulcerative colitis and cirrhosis of the liver. Due to limited understanding of the etiology and mechanism of PSC, the only existing treatment option is orthotopic liver transplantation (OLT); however, recurrence of PSC, after OLT is estimated to be between 5% and 35%. We discuss the successful treatment of a pediatric patient, with recurrent PSC, after OLT with oral Vancomycin.

Beaded bile ducts in primary sclerosing cholangitis

2019 ◽  
Vol 44 (3) ◽  
pp. 1195-1196 ◽  
Author(s):  
Dario Giambelluca ◽  
Claudio Leto ◽  
Francesco D’Arpa ◽  
Massimo Midiri ◽  
Giuseppe Salvaggio
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Bile Ducts

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 Characteristic Findings of Primary Sclerosing Cholangitis on Endoscopic Retrograde Cholangiography: Which is the Most Common Finding?

2011 ◽  
Vol 5 ◽  
pp. CGast.S7850
Author(s):  
Amir Houshang Mohammad Alizadeh ◽  
Anahita Shahnazi ◽  
Aida Rasoulzadeh ◽  
Esmaeel Shams ◽  
Manijeh Mohammadi ◽  
...  
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Laboratory Data ◽  
Specific Pattern ◽  
Common Type ◽  
Endoscopic Retrograde Cholangiography ◽  
Common Finding ◽  
Cholestatic Liver Disease ◽  
Endoscopic Retrograde ◽  
Small Duct

Background Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease and one of the most common indications for liver transplantation in adults. There are conflicting data regarding characteristic findings of PSC disease on endoscopic retrograde cholangiography (ERCP). We undertook this study to clarify whether there is a specific pattern of involvement of the biliary tract in patients with PSC and to evaluate features of PSC disease on ERCP in order to be able to manage this disease better. Methods This retrospective study included 45 patients admitted to Taleghani Hospital in 2004-2010 and diagnosed to have PSC on the basis of typical cholangiographic findings in combination with clinical and laboratory data. Patients suspected to have secondary sclerosing cholangitis were excluded. Demographic and clinical data were recorded, along with cholangiographic findings and the frequency of large duct and small duct PSC. Results Forty-five patients of mean age 34.8 (range 15-66) years were included. Twenty-nine patients (64.4%) had inflammatory bowel disease, and the frequency of large duct PSC and small duct PSC was 93.4% and 6.6%, respectively. The intrahepatic ducts alone were involved in 11 (24.4%) patients and the extrahepatic ducts were involved in 14 (31.1%), with 17 (37.7%) patients having both intrahepatic and extrahepatic PSC. Three (6.6%) patients did not have bile duct involvement on ERCP, and their disease was diagnosed by liver biopsy as small duct PSC. The most common type of cholangiographic feature of intrahepatic duct involvement was type 2, found in 15 (33.3%) patients, with type 3 being the most common type of extrahepatic duct involvement and detected in 16 (35.5%) patients. Conclusion Our study demonstrates that the most common PSC finding on ERCP is involvement of both the extrahepatic and intrahepatic bile ducts, with small duct PSC being less common than large duct PSC.

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