[Frontiers in Bioscience E4, 1683-1705, January 1, 2012]

Primary sclerosing cholangitis: etiopathogenesis and clinical management

Asha Gupta,1 Christopher L. Bowlus2

1Department of Internal Medicine, University of California Davis Health System, 4150 V Street, Sacramento, CA 95817, 2Division of Gastroenterology and Hepatology, University of California Davis Health System, 4150 V Street, Sacramento, CA 95817

TABLE OF CONTENTS

1. Abstract
2. Features of PSC
2.1. Epidemiology
2.2. Clinical features
2.3. Biochemical features
2.4. Serologic features
2.5. Radiographic features
2.6. Histologic features
2.7. Diagnostic criteria
2.7.1. Small duct PSC
2.7.2. PSC-AIH overlap
2.8. Clinical course and prognosis
3. Etiopathogenesis
3.1. Genetic susceptibility
3.1.1. HLA and related genes
3.1.2. IBD shared loci
3.2. Innate immune responses
3.3. Lymphocyte trafficking
3.4. Toxic bile
4. Clinical management
4.1. Medical therapy
4.2. PSC-associated complications
4.2.1. Pruritus
4.2.2. Dominant strictures
4.2.3. Cholangiocarcinoma
4.2.4. Metabolic diseases
4.2.5. Gallbladder disease
4.3. Complications of Cirrhosis
4.3.1. Peristomal varices
4.3.2. Liver transplantation
5. Summary and perspective
6. References

1. ABSTRACT

Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease characterized by the destruction of medium to large-sized bile ducts and intense, concentric fibrosis. Complications from PSC include bacterial cholangitis, cirrhosis, and cholangiocarcinoma and a therapy that might alter the natural history of the disease remains lacking. Our understanding of the pathogenesis of PSC also remains rudimentary but several theories exist, suggesting roles for genetic susceptibility, abnormal innate immune responses lymphocyte trafficking, and toxic bile formation. Medical and surgical therapies, short of liver transplantation, have been disappointing. Currently, the management of PSC is aimed largely at the endoscopic treatment of dominant biliary strictures and complications of cholestasis until the disease has progressed to cirrhosis, at which time liver transplantation is indicated. Progress in our basic understanding of PSC is desperately needed in order to rationally design new therapeutic approaches to this disease.