Evolving Concepts in Primary Sclerosing Cholangitis
Evolving Concepts in Primary Sclerosing Cholangitis
Patients suffering from primary sclerosing cholangitis (PSC) show considerable differences regarding clinical manifestations (i.e. large duct versus small-duct PSC, presence or absence of concomitant inflammatory bowel disease), disease progression, risk for malignancy and response to therapy, raising the question whether PSC may represent a mixed bag of diseases of different aetiologies. The growing list of secondary causes and diseases 'mimicking' or even overlapping with PSC (e.g. IgG4-associated sclerosing cholangitis), which frequently causes problems in clear-cut discrimination from classic PSC and the emerging knowledge about potential disease modifier genes (e.g. variants of CFTR, TGR5 and MDR3) support such a conceptual view. In addition, PSC in children differs significantly from PSC in adults in several aspects resulting in distinct therapeutic concepts. From a clinical perspective, appropriate categorization and careful differential diagnosis are essential for the management of concerned patients. Therefore, the aim of the current review is to summarize current and evolving pathophysiological concepts and to provide up-to-date perspectives including future treatment strategies for PSC.
Primary sclerosing cholangitis (PSC) represents a chronic cholestatic liver disease of unidentified aetiology and unknown pathogenesis. It is a progressive disease characterized by inflammation, fibrosis and strictures of the intra- and/or extrahepatic bile ducts which finally leads to biliary cirrhosis in almost all cases. The lack of effective medical treatment for PSC is reflected by the frequent need for liver transplantation (LT). In addition, PSC patients are at high risk to develop cholangiocarcinoma (CCA), colorectal cancer (CRC) and pancreatic carcinoma. Consequently, PSC represents a precancerous disorder and potentially fatal disease. Prognosis is poor and the estimated 10-year survival is approximately 65% with large inter-individual variation. Long-term prognosis of primarily asymptomatic PSC and small duct PSC (i.e. a variant of PSC affecting exclusively bile ducts at the microscopic level) is significantly better compared with classic PSC. Establishment of diagnosis is especially challenging and up-to-now, apart from LT, no curative treatment options are available.
Abstract and Introduction
Abstract
Patients suffering from primary sclerosing cholangitis (PSC) show considerable differences regarding clinical manifestations (i.e. large duct versus small-duct PSC, presence or absence of concomitant inflammatory bowel disease), disease progression, risk for malignancy and response to therapy, raising the question whether PSC may represent a mixed bag of diseases of different aetiologies. The growing list of secondary causes and diseases 'mimicking' or even overlapping with PSC (e.g. IgG4-associated sclerosing cholangitis), which frequently causes problems in clear-cut discrimination from classic PSC and the emerging knowledge about potential disease modifier genes (e.g. variants of CFTR, TGR5 and MDR3) support such a conceptual view. In addition, PSC in children differs significantly from PSC in adults in several aspects resulting in distinct therapeutic concepts. From a clinical perspective, appropriate categorization and careful differential diagnosis are essential for the management of concerned patients. Therefore, the aim of the current review is to summarize current and evolving pathophysiological concepts and to provide up-to-date perspectives including future treatment strategies for PSC.
Introduction
Primary sclerosing cholangitis (PSC) represents a chronic cholestatic liver disease of unidentified aetiology and unknown pathogenesis. It is a progressive disease characterized by inflammation, fibrosis and strictures of the intra- and/or extrahepatic bile ducts which finally leads to biliary cirrhosis in almost all cases. The lack of effective medical treatment for PSC is reflected by the frequent need for liver transplantation (LT). In addition, PSC patients are at high risk to develop cholangiocarcinoma (CCA), colorectal cancer (CRC) and pancreatic carcinoma. Consequently, PSC represents a precancerous disorder and potentially fatal disease. Prognosis is poor and the estimated 10-year survival is approximately 65% with large inter-individual variation. Long-term prognosis of primarily asymptomatic PSC and small duct PSC (i.e. a variant of PSC affecting exclusively bile ducts at the microscopic level) is significantly better compared with classic PSC. Establishment of diagnosis is especially challenging and up-to-now, apart from LT, no curative treatment options are available.