Scientific Research
This page is in a'blog' format with the latest scientific PSC research identified by Google Scholar, Readbyqmx.com and other sources added regularly.

New paradigms in the treatment of hepatic cholestasis: From UDCA to FXR, PXR and beyond

Ulrich Beuers, Michael Trauner, Peter Jansen, Raoul Poupon


Summary:
Cholestasis is an impairment of bile formation/flow at the level of the hepatocyte and/or cholangiocyte. The first, and for the moment, most established medical treatment is the natural bile acid (BA) ursodeoxycholic acid (UDCA). This secretagogue improves, e.g. in intrahepatic cholestasis of pregnancy or early stage primary biliary cirrhosis, impaired hepatocellular and cholangiocellular bile formation mainly by complex post-transcriptional mechanisms. The limited efficacy of UDCA in various cholestatic conditions urges for development of novel therapeutic approaches. ... Please click here to read the full article and/or download the article as a PDF.


Journal of Herpetology, April 2015, Volume 62, Issue 1, Supplement, pp S25-37
DOI: http://dx.doi.org/10.1016/j.jhep.2015.02.023

Risk Factors for Recurrent Primary Sclerosing Cholangitis After Liver Transplantation

Reena Ravikumar, Emmanuel Tsochatzis, Sophie Jose, Michael Allison, Anuja Athale, Felicity Creamer, Bridget Gunson, Vikram Iyer, Mansoor Madanur, Derek Manas, Andrea Monaco, Darius Mirza, Nicola Owen, Keith Roberts, Gourab Sen, Parthi Srinivasan, Stephen Wigmore, Giuseppe Fusai, Bimbi Fernando, Andrew Burroughs

BACKGROUND AND AIMS: 
The association between Primary Sclerosing Cholangitis (PSC) and Inflammatory Bowel Disease (IBD) is well recognised. However, the relationship between IBD and recurrent PSC (rPSC) is less well understood. We assessed the prevalence of rPSC and analysed the factors associated with rPSC post liver transplantation and its influence on graft and patient survival.

METHODS: 
This is a UK multicentre observational cohort study across six of the seven national liver transplant (LT) units. All patients undergoing a first LT for PSC between January 1 1990 and December 31 2010 were included ... Please click here to read the remainder of the abstract.

Journal of Hepatology 2015 July 14

Activation of biliary tree stem cells within peribiliary glands in primary sclerosing cholangitis

Guido Carpino, Vincenzo Cardinale, Anastasia Renzi, Johannes R Hov, Pasquale Bartolomeo Berloco, Massimo Rossi, Tom H Karlsen, Domenico Alvaro, Eugenio Gaudio

BACKGROUND & AIMS: 
Primary sclerosing cholangitis (PSC) is characterised by fibro-stenosing strictures involving extrahepatic and/or large intrahepatic bile ducts. Mechanisms leading to bile duct injury are poorly understood. We aimed to study the biliary tree stem cell compartment located in peribiliary glands of extra-hepatic and large intra-hepatic bile ducts and its role in the pathogenesis of biliary fibrosis in PSC.

METHODS: 
Specimens containing extrahepatic or large intrahepatic bile ducts were obtained from normal liver (n=6), liver explants from patients with PSC (n=11), and primary biliary cirrhosis (n=6).  ... Please click here to read the remainder of the abstract.

Journal of Hepatology 2015 June 25

Inflammation but not Biliary Obstruction is Associated With Level of CA19-9 in Patients with Primary Sclerosing Cholangitis

Andreas Wannhoff, Christian Rupp, Kilian Friedrich, Maik Brune, Johannes Knierim, Christa Flechtenmacher, Peter Sauer, Wolfgang Stremmel, Johannes R Hov, Peter Schirmacher, Karl Heinz Weiss, Daniel N Gotthardt

BACKGROUND & AIMS: 
Assays that measure serum level of carbohydrate antigen 19-9 (CA19-9) are used to screen patients with primary sclerosing cholangitis (PSC) for malignancies. However, in patients with PSC, cholestasis, and bacterial cholangitis, the level of CA19-9 can be affected by variants in the fucosyltransferases 2 and 3 genes (FUT2 and FUT3), which regulate production of CA19-9. We investigated how these genotypes affect cancer screening in these patients.

METHODS: 
We performed a retrospective analysis of data from 209 patients with PSC (19 with biliary malignancy, 23 with cholestasis and bacterial cholangitis) treated at the University Hospital Heidelberg from 1987 through 2014. We collected data on maximum serum level of CA19-9; laboratory measures of cholestasis or inflammation; the presence of dominant stenosis, cholestasis, and bacterial cholangitis; and FUT2 and FUT3 genotypes ... Please click here to read the remainder of the abstract.

Clinical Gastroenterology and Hepatology 2015 July 17

Applicability and Prognostic Value of Histologic Scoring Systems in Primary Sclerosing Cholangitis

Elisabeth M G de Vries, Joanne Verheij, Stefan G Hubscher, Mariska M R Leeflang, Kirsten Boonstra, Ulrich Beuers, Cyriel Y Ponsioen

BACKGROUND: 
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease. At present there is no appropriate histologic scoring system available for PSC, evaluating both degree of necroinflammatory activity (grade) and fibrosis (stage). Aim of this study was to assess if three scoring systems, commonly used in different liver diseases could be applied for grading and/or staging of PSC.

METHODS: 
Sixty-four PSC patients from a Dutch cohort, who underwent diagnostic liver biopsy, were included. Staging was scored using Ishak, Nakanuma, and Ludwig systems. Grading was scored using Ishak and Nakanuma systems. Three measures of outcome were defined; transplant-free survival, time to liver transplantation (LTx) and occurrence of cirrhosis related symptoms (CRS). ... Please click here to read the remainder of the abstract.

Journal of Hepatology 2015 June 18

Spectrum of biliary complications following live donor liver transplantation

Priya Simoes, Varun Kesar and Jawad Ahmad

Liver transplantation is the optimal treatment for many patients with advanced liver disease, including decompensated cirrhosis, hepatocellular carcinoma and acute liver failure. Organ shortage is the main determinant of death on the waiting list and hence living donor liver transplantation (LDLT) assumes importance. Biliary complications are the most common post operative morbidity after LDLT and occur due to anatomical and technical reasons. They include biliary leaks, strictures and cast formation and occur in the recipient as well as the donor. The types of biliary complications after LDLT along with their etiology, presenting features, diagnosis and endoscopic and surgical management are discussed.  Please click here to read the full article.

World J Hepatol. 2015 July 18; 7(14): 1856-1865. 
Published online 2015 July 18. doi: 10.4254/wjh.v7.i14.1856.

Study shows regions of genome underlying IBD consistent around the world

The first genetic study of inflammatory bowel disease (IBD) to include individuals from diverse populations has shown that the regions of the genome underlying the disease are consistent around the world. This study, conducted under the auspices of the International IBD Genetics Consortium, included nearly 10,000 DNA samples from people of East Asian, Indian or Iranian descent and an existing set of 86,640 samples drawn from across Europe, North America and Oceania. ...  Please click here to read the full article with the option to print as a PDF

Outcome of patients with primary sclerosing cholangitis and ulcerative colitis undergoing colectomy

Sombat Treeprasertsuk, Einar Björnsson, Emmanouil Sinakos, Emma Weeding, Keith D Lindor

AIM: 
To study the outcomes of primary sclerosing cholangitis (PSC) patients with ulcerative colitis (UC) undergoing colectomy.

METHODS: 
We identified 193 patients with PSC and UC undergoing colectomy at the Mayo Clinic (Rochester, MN, United States), between January 1, 1995 and December 31, 2008 using a computerized record system. Eighty-nine patients were excluded due to unclear diagnosis, liver transplantation prior to colectomy, age less than 18 years, inadequate follow-up data or known cases of cholangiocarcinoma. We retrospectively reviewed data from patient medical records. Clinical information, date of colectomy, preoperative and follow-up liver tests and pathological findings of the colon were reviewed. The Mayo risk score at baseline was calculated to obtain survival estimates for up to 4 years of follow-up.  ... Please click here to read the remainder of the abstract

World Journal of Gastrointestinal Pharmacology and Therapeutics 2013 August 6, 4 (3): 61-8