Autoimmune hepatitis/sclerosing cholangitis overlap syndrome in childhood: A 16-year prospective study

Abstract

To investigate whether sclerosing cholangitis with an autoimmune serology characteristic of autoimmune hepatitis (AIH) and AIH are distinct entities, we studied 55 consecutive children with clinical and/or biochemical evidence of liver disease and circulating antinuclear (ANA), anti-smooth muscle (SMA), and/or liver-kidney-microsomal type 1 (LKM1) autoantibodies. They underwent liver biopsy, direct cholangiography, sigmoidoscopy, and rectal biopsy at presentation. Twenty-eight were diagnosed as AIH in the absence and 27 autoimmune sclerosing cholangitis (ASC) in the presence of radiological features of cholangiopathy. Twenty-six ASC and 20 AIH had ANA and/or SMA; 1 ASC and 8 AIH LKM1 autoantibody. Similarities between the 2 conditions included most clinical and biochemical parameters and a lower frequency of HLA DR4. Inflammatory bowel disease and histological biliary changes were more common in ASC; coagulopathy, hypoalbuminemia, lymphocytic periportal hepatitis, and HLA DR3 were more common in AIH. Histological biliary changes were observed in 65% of ASC and 31% of AIH patients. Eighty-nine percent responded to immunosuppression. Follow-up liver biopsies from 17 ASC and 18 AIH patients had similarly reduced inflammatory activity and no progression to cirrhosis. Sixteen follow-up cholangiograms from AIH patients and 9 from ASC patients were unchanged, while 8 ASC patients showed a progressive cholangiopathy. One child with AIH and ulcerative colitis developed sclerosing cholangitis 8 years after presentation. At 2 to 16 years (median, 7 years) from presentation, all patients are alive, including 4 ASC patients who underwent liver transplantation. In conclusion, ASC and AIH are similarly prevalent in childhood; cholangiography is often needed to distinguish between these 2 entities, which are likely to lie within the same disease process.