Current Concepts in Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis

Abstract

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are chronic, cholestatic diseases of the liver with common clinical manifestations. Early diagnosis and treatment of PBC slows progression and decreases the need for transplant. However, one-third of patients will progress regardless of treatment. Bilirubin <1.0 and alkaline phosphatase <2.0 x the upper limit of normal at 1 year after treatment appear to predict 10-year survival. Ursodeoxycholic acid (UDCA) is the recommended treatment for PBC, and recent studies with obeticholic acid showed promising results for UDCA non-responders. Unlike PBC, no therapy has been shown to alter the natural history of PSC. The recommended initial diagnostic test for PSC is magnetic resonance cholangiopancreatography, typically showing bile duct wall thickening, focal bile duct dilatation, and saccular dilatation of the intra- and/or extrahepatic bile ducts. Immunoglobulin 4-associated cholangitis must be excluded when considering the diagnosis of PSC, to allow for proper treatment, and monitoring of disease progression. In addition to the lack of therapy, PSC is a pre-malignant condition and close surveillance is indicated.

Figure 1

Liver histology in primary biliary cirrhosis (PBC). (a) Photomicrograph of an hematoxylin and eosin (H & E) stain (x200 magnification) from a percutaneous liver biopsy demonstrating a classic florid duct lesion in a patient with PBC. (b) Immunostaining of the portal tract in a with anti-cytokeratin-7 highlighting the bile duct that is infiltrated with lymphocytes. Courtesy of Nilesh Kashikar MD, PhD (University of Miami).

Figure 2

Cholangiograms in PSC. (a) Cholangiogram from MRCP. (b) Cholangiogram from ERCP. Legend: 41-year-old female diagnosed with PSC 1 year prior, presenting with marked cholestasis and elevation of her liver chemistries who underwent MRCP showing beading and stricturing of the intrahepatic left ductal system and a dominant stricture in the right main hepatic duct. ERCP confirmed these findings, and the right hepatic duct was dilated. Brushings were negative for malignancy and FISH was negative for polysomy. Photos: courtesy of Enrico Souto, MD (University of Miami). ERCP, endoscopic retrograde cholangiopancreatography; FISH, fluorescence in situ hybridization; MRCP, magnetic resonance cholangiopancreatography; PSC, primary sclerosing cholangitis.

Figure 3

Proposed algorithm for UDCA use in clinical practice. Modified from ref. 96. *Surveillance and management options reviewed on cancer surveillance section. **Referral to cholestatic liver disease specialist and/or tertiary care center for consultation may be advisable. CA 19-9, carbohydrate antigen 19-9; MRCP, magnetic resonance cholangiopancreatography.