Management of patients with primary biliary cirrhosis: a practical guide

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease that predominantly occurs in middle-aged women. It is characterised by inflammatory destruction of interlobular and septal bile ducts, subsequent fibrosis, and finally liver cirrhosis. The disease slowly progresses over decades and may lead to liver failure. It is more frequently diagnosed now than it was in the past probably because of a greater awareness of the disease. Liver function tests reveal an elevation of serum alkaline phosphatase and micro-glutamyltransferase levels with or without elevated aminotransferase levels. Antimitochondrial antibodies (AMAs) are found in 95% of patients with PBC. AMAs have been shown to be directed against the 2-oxo-acid dehydrogenase complexes located on the inner membrane of the mitochondria. However, AMA titres do not correlate with disease severity or progression, and the role of AMAs in the pathogenesis of primary biliary cirrhosis is not yet known. The disease is frequently associated with other autoimmune disease, including Sjogren's syndrome, thyroid disorders and scleroderma. Most therapeutic efforts have been directed at altering the immune response. Ursodeoxycholic acid (UDCA) appears to be effective therapy in preventing or delaying the need for liver transplantation and improving survival. However, a number of patients receiving UDCA still develop progressive disease and go on to transplantation, which is an effective therapy at the end stage of the disease. Various prognostic models have been proposed to assist in the determination of the optimum timing of liver transplantation.