Development of Autoimmune Hepatitis in Primary Biliary Cirrhosis

Andrea A. Gossard; Keith D. Lindor


Liver International. 2007;27(8):1086-1090. 

In This Article

Abstract and Introduction


Aim/Background: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of unknown aetiology. Up to 10% of patients with typical features of PBC will have additional features of autoimmune hepatitis (AIH). A subset, however, have no such features but go on to develop a "sequential" AIH overlap syndrome.
Objectives: Describe our experience with eight patients who developed AIH after the diagnosis of PBC was made.
Methods: We reviewed the charts of all PBC patients over a 9-year period (from 1996 to 2005). Only PBC patients with no features of AIH were included.
Results: There were 1476 patients with PBC. Of these, eight patients developed features of AIH overlap syndrome based on biochemical and histological parameters. Treatment included prednisone and azathioprine for 24 or more months. The majority of patients remained on ursodeoxycholic acid (UDCA) throughout treatment. Response to therapy was defined by improvement in enzymes, and was rapid for all patients. One patient was able to discontinue treatment with prednisone and azathioprine, while seven have continued on therapy to date.
Conclusions: A "sequential" overlap syndrome of AIH with PBC can occur. Treatment with prednisone and azathioprine may lead to a rapid improvement in aminotransferase levels.


Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease that is characterized by gradual destruction of the interlobular bile ducts that leads to damage of the hepatocytes. The aetiology remains unknown. The rate of disease progression is quite variable, but typically the disease is slowly progressive.[1] Some patients never progress from an asymptomatic state, although most will develop symptoms over time. Fortunately, only a few develop rapidly progressive bile duct loss progressing to liver failure. The median survival for untreated asymptomatic disease is 16 years and 7.5 years for symptomatic disease.[2]

Nearly 90% of patients with PBC are female. Approximately 10% of patients who have all the features of PBC present with additional features of autoimmune hepatitis (AIH). These features include other autoantibodies such as smooth muscle antibodies, hypergammaglobulinaemia with a five-fold elevation of aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT), or a 10-fold elevation of the AST. Histologically, these patients may have lymphoplasmacytic interface hepatitis in addition to the typical florid duct lesions present in PBC.

Other patients, however, have only typical findings of PBC at the time of diagnosis, and then go on to develop changes consistent with AIH eventually. Very little research has been carried out on this population. A recent paper[3] described two such cases. Each involved a patient diagnosed with PBC only to develop AIH 1-2 years later. This "sequential" development of AIH in the setting of PBC is the focus of this paper.

Standard treatment for PBC consists of ursodeoxycholic acid (UDCA) at a dose of 13-15 mg/kg of the body weight. An analysis of more than 500 patients treated for up to 4 years initially with either UDCA or placebo, with most placebo patients converting to UDCA after 2 years of therapy, indicates that treatment with UDCA was associated with a delay in the need for transplantation or of death.[4] For patients with early-stage disease histologically (stages 0-2), who are on UDCA therapy, the clinical course is quite good.[5] One study suggested that the 20-year outlook for patients with early-stage disease on UDCA therapy was comparable with a matched population of people without the disease.[6]

Standard treatment for AIH is prednisone and azathioprine.[7] Therapy may be continued for 24 months or longer in some patients. Treatment for AIH in the setting of PBC is not well described in the literature. We describe our experience with eight patients with sequential development of AIH in the setting of well-established PBC.


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