Co-occurrence of Idiopathic Granulomatous Hepatitis and Primary Biliary Cirrhosis

Abstract

Purpose: Purpose: To report a possible association between idiopathic granulomatous hepatitis and primary biliary cirrhosis (PBC). Methods: Review of two cases Case 1: A 42 year old asymptomatic woman had an elevated alkaline phosphatase, 343 IU (normal <130), a positive antimitochondrial antibody, titer 1:64, and 20% eosinophils. Liver biopsy demonstrated florid bile duct lesions with minimal fibrosis, consistent with Stage II PBC. She was treated with methotrexate 15 mg weekly (ursodiol was unavailable at the time). Six months later her alkaline phosphatase was normal, 75 IU. 15 years after the diagnosis of PBC the patient presented with one week of fevers, chills, and night sweats. Her alkaline phosphatase was elevated, 313 IU. Liver biopsy showed numerous granulomas with giant cells throughout the liver lobule with some areas of palisading necrosis and intense inflammation, consistent with a diagnosis of idiopathic granulomatous hepatitis. The methotrexate dose was increased to 22.5 mg per week. Her symptoms remitted, alkaline phosphatase returned to normal, and liver biopsy was essentially normal. Case 2: A 42 year old female with fatigue was referred for evaluation of abnormal liver function tests. Her alkaline phosphatase level was slightly elevated, 149 IU (normal <125). Antimitochondrial antibody was negative. Liver biopsy showed a granulomatous type inflammation of the portal tracts consistent with idiopathic granulomatous hepatitis. She was treated with oral methotrexate; two and seven years later liver biopsies and alkaline phosphatase levels were essentially normal. 12 years after diagnosis of idiopathic granulomatous hepatitis, alkaline phosphatase was 284 IU, antimitochondrial antibody was strongly positive (113.2 units by ELISA; normal <20), and liver biopsy showed bile duct inflammation and occasional fibrous bridging, consistent with a diagnosis of Stage II-III PBC. Ursodiol therapy was initiated. Alkaline phosphatase has since ranged from 115 - 149 IL (normal <130). Idiopathic granulomatous hepatitis is a rare disease of unknown cause which is characterized by recurrent fevers, sweats, and granulomas in portal and lobular regions of the liver. We describe the first reported case of idiopathic granulomatous hepatitis occurring in a patient with PBC, as well as the first known diagnosis of PBC in a patient with idiopathic granulomatous hepatitis. Our experience with these patients suggests that idiopathic granulomatous hepatitis and PBC can occur in the same individual. The cause of both diseases is unknown.