Options for treatment of primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is a chronic progressive cholestatic disease where there is progressive, granulomatous destruction of the middle-sized bile ducts. The disease affects mainly middle-aged women. The association with other autoimmune diseases and the widespread disturbance of the humoral and cellular immune systems has led to the inclusion of PBC as an autoimmune disease. However, there are several lines of evidence that suggest that both host and environmental factors are implicated in triggering the disease. Without a clear aetiology, it is difficult to find a logical approach to treatment. Well constructed clinical trials are difficult to run because of the variable and long natural history of the disease; and suitable endpoints are difficult to define and validated surrogate endpoints have not been defined. The only drug licensed for use is the bile acid, ursodeoxycholic acid. This drug is associated with significant biochemical improvement and improvement in the immunological disturbances (including a reduction in the titre of the diagnostic autoantibody, antimitochondrial antibody), but the effect on survival and histological progression is still controversial. There is little effect on symptoms. Nonetheless, its safety and lack of toxicity have meant that it has become the drug of choice and most studies now assess the effect of additional treatments. Many other agents have been studied. There is some evidence, from prospective, controlled studies, for a beneficial effect of azathioprine and ciclosporin (cyclosporine); evidence for a beneficial effect of corticosteroids and of mycophenolate is limited and there is little firm evidence for a beneficial effect of methotrexate, penicillamine, thalidomide or colchicine. Other treatments being evaluated include fibric acid derivatives (fibrates), NSAIDs and leukotriene antagonists. Liver transplantation remains the only option for end-stage disease but recurrence of disease may be found in the graft. Experimental therapies include antiretroviral therapy. Symptomatic treatment is required for pruritus and the mainstays are the bile acid binding agents such as colestyramine. For those who are intolerant of the drug or where it is ineffective, rifampicin and naltrexone may be effective. There is no effective treatment for the associated lethargy.