LAUSR

A 38-year-old woman with morbid obesity, gastroesophageal reflux disease, and seronegative rheumatoid arthritis that were treated with sulfasalazine and hydroxychloroquine was referred to our gastroenterology and hepatology clinic for evaluation of abnormal liver function tests (LFTs) notable for alanine aminotransferase (ALT) 74 U/L, aspartate aminotransferase (AST) 66 U/L, and alkaline phosphatase (AP) 201 U/L. Although ultrasound was negative for biliary obstruction, interestingly, she had elevated mitochondrial antibodies (AMA; 1:640 titer) and smooth muscle antibodies (SMA; 49U]). Otherwise, her total bilirubin (0.6 mg/dL), albumin (4.5 g/dL), total protein (7.3 g/dL), platelet count (220,000/μL), and INR (1.1) were normal. These laboratory findings were concerning for primary biliary cholangitis (PBC) and/or autoimmune hepatitis (AIH). Symptomatically, the patient only reported fatigue and denied pruritus, jaundice, or xanthomas. Physical examination did not show any stigmata of cirrhosis. She underwent testing for other causes of elevated transaminases, including a viral hepatitis panel, ceruloplasmin, transglutaminase IgA, anti-gliadin IgG and IgA, and thyroid-stimulating hormone that were all unremarkable. Autoimmune testing for anti-dsDNA and the extractable nuclear antigens SS-A Ab, SS-B Ab, and anti-SM/ribonucleic protein (RNP), in addition to rheumatoid factor, complement 3, and complement 4, were also all normal. Liver histology showed chronic hepatitis with mixed portal and lobular inflammation without granulomatous destructive cholangitis or bile duct loss to suggest PBC or an overlap syndrome. The biopsy sample was of adequate size being 2.5 cm long, 0.1 cm in diameter, and including nine portal tracts. These histologic findings were most suggestive of AIH (Fig. 1). Despite the lack of florid duct lesions, the elevated AMA (which was persistently high even with repeat testing) and the elevated AP continued to be concerning for PBC. We discussed our concerns for both AIH and PBC with the patient. Given that PBC treatment with ursodiol was more benign than AIH treatment with prednisone and azathioprine, we trialed ursodiol; unfortunately, despite several months of ursodiol treatment, her LFTs and fatigue remained unchanged. Therefore, we decided to alter our treatment and target AIH instead. She was prescribed a 1-month prednisone taper (starting at 30 mg/day) with azathioprine. Due to miscommunication, she did not take her azathioprine and only took the prednisone taper. Nevertheless, her symptoms and LFTs improved after 2 weeks of treatment (AST 17 U/L, ALT 25 U/L, AP 143 U/L). She decided not to return to gastroenterology clinic since her symptoms had resolved. She was seen in clinic again one and a half years later when her symptoms and transaminitis relapsed (AST 57 U/L, ALT 63 U/L, AP 266 U/L). Given her previous response to prednisone, she was started on prednisone and azathioprine. Unexpectedly, she did not respond to the combination therapy despite 2 months of treatment. A repeat liver biopsy showed portal inflammation with nonnecrotizing granulomas consistent with PBC (Figs. 2, 3). The biopsy sample included multiple cores that were each 0.7 cm in length, 0.1 cm in diameter, and contained at least six to seven portal tracts for evaluation. Given the change in histology, the prednisone and azathioprine were stopped and the patient was subsequently started on ursodiol, which resolved her symptoms and normalized the transaminases and AP after 1 month of treatment (Fig. 4).