Diagnosis and management of primary biliary cirrhosis

Abstract

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized histologically by destruction of intrahepatic bile ducts and serologically by the presence of antimitochondrial antibodies. The incidence and prevalence of PBC are increasing. Fatigue and pruritus are common symptoms in PBC, although the proportion of asymptomatic PBC is increasing due to the widespread use of screening biochemical tests and antimitochondrial antibody assays. PBC may eventually lead to cirrhosis and its consequent complications. In the 1980s, PBC was the leading indication for liver transplantation. Ursodeoxycholic acid is the only US FDA-approved therapeutic agent for PBC. Clinical trials have shown that the use of ursodeoxycholic acid in PBC results in reduction of liver biochemistries, a delay in histological progression, a delay in the development of varices and improvement in survival without liver transplantation.

Keywords::

• antimitochondrial antibody
• liver transplantation
• primary biliary cirrhosis
• ursodeoxycholic acid

Financial & competing interests disclosure

KD Lindor is an unpaid advisor for Lumena and Intercept. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by destruction of the intrahepatic bile ducts. It may eventually lead to cirrhosis and its complications such as portal hypertension and hepatocellular carcinoma.

• The serological hallmark of PBC is the antimitochondrial antibody (AMA), present in nearly 95% of patients. ELISA is the most widely used method by the commercial laboratories for the detection of AMA.

• AMAs are absent in 5% of patients with PBC.

• Symptoms and conditions associated with PBC are fatigue, pruritus, osteopenic bone disease, autoimmune hepatitis, scleroderma, Sicca syndrome and Raynaud’s phenomenon.

• The diagnosis of PBC requires the establishment of persistently elevated serum alkaline phosphatase and presence of AMA. In such scenario, liver biopsies are not required.

• Liver biopsies are required in the setting of cholestasis and absence of AMA in order to establish a diagnosis of PBC.

• Ursodeoxycholic acid is safe and effective in the majority of patients with PBC, and is the only US FDA-approved agent in PBC. Dosing is important. Currently, the recommended dose is 13–15 mg/kg/day.

• The use of ursodeoxycholic acid in PBC prolongs the survival without liver transplantation.

• The liver transplantation burden of PBC in the USA decreased between 1995 and 2006.