PRIMARY BILIARY-CIRRHOSIS AUTOIMMUNE HEPATITIS OVERLAP SYNDROME - CLINICAL-FEATURES AND RESPONSE TO THERAPY

The association of primary biliary cirrhosis (PBC) and autoimmune hepa titis (AIH) is thought to be rare, and its optimal treatment is unknow n. Of 130 consecutive patients with a diagnosis of PBC, we identified 12 cases (9.2%) of overlap syndrome (10 females, 2 males; median age, 50 years) strictly defined by the presence of at least two of the thre e recognized biochemical, serological, and histological criteria of ea ch disease. One patient had initially pure PBC and developed AIH chara cterized by a flare of alanine transaminase (ALT) (1,330 IU/L; N < 35) , elevated immunoglobulin G (IgG) (42 g/L; N < 14.0), and presence of anti-smooth muscle antibodies (ASMA) after 20 months of ursodeoxycholi c acid (UDCA) therapy. A complete clinical and biochemical remission w as achieved under combination of corticosteroids and UDCA, Eleven pati ents had features of both diseases at presentation: high serum levels of alkaline phosphatase (AP) (median; 250 IU/L; N < 100), ALT (140 IU/ L), and IgG (30.8 g/L), presence of mitochondrial antibodies (n = 9) o r ASMA (n = 9;), florid bile duct lesions (n = 8), and moderate or sev ere periportal or periseptal lymphocytic piecemeal necrosis (n = 11), UDCA (13-15 mg/kg/d) given alone in 5 patients induced a significant d ecrease in biochemical cholestasis but not in ALT levels, and liver fi brosis progressed in 3 patient's. Corticosteroids given alone in 6 pat ients induced a significant decrease in ALT, IgG, and AP levels, but n one had a biochemical normalization, The patients with pe persistently abnormal liver tests under either UDCA or corticosteroids received bo th UDCA and corticosteroids. A further marked biochemical improvement was observed, and all patients became asymptomatic. We conclude that, in patients with PBC: 1) overlap syndrome with AIH is not rare; 2) fla res of AIH may occur either spontaneously or under UDCA; and 3) combin ation of UDCA and corticosteroids is required in most patients to obta in a complete biochemical response. Overlap syndrome may represent an important and unrecognized cause of resistance to UDCA in patients wit h PBC.