S5798 Azathioprine-Induced Acute Pancreatitis in Autoimmune Hepatitis: A Rare but Important Adverse Event

Introduction: Azathioprine-induced pancreatitis (AIP) is an idiosyncratic, dose-independent reaction manifesting 3-6 weeks after drug initiation and resolving 1-11 days after withdrawal. In autoimmune hepatitis (AIH), AIP incidence is low (∼1.5%) compared to incidence of same drug reaction reported in patients with inflammatory bowel disease (IBD) especially Crohn’s disease, here we present one such case. Case Description/Methods: A 67-year-old woman with recently diagnosed AIH presented with 3 days of abdominal pain, nausea, vomiting, fever, and chills. Two months earlier, she was found to have elevated liver enzymes in hepatocellular predominant patter, ANA 1:1280, and ASMA 1:80. Liver biopsy revealed chronic hepatitis with portal lymphoplasmacytic infiltrates and occasional eosinophils, consistent with AIH. She was started on budesonide, with azathioprine (AZA) added 3 weeks prior to presentation. Both were discontinued 3 days before admission due to fevers and chills. On admission, she was febrile to 38.5°C and tachycardic to 115 bpm. She had diffuse abdominal pain on palpation. Labs showed lipase 2,000 U/L, white blood cell 4.5 × 10³/µL, Hgb 11.5 mg/dl, platelets 143 × 10³/µL, normal liver function tests and lipid panel, and IgG4 of 123.6 mg/dL. CT abdomen demonstrated mild pancreatic stranding and a dilated common bile duct (10 mm). MRCP showed a distended gallbladder without stones or choledocholithiasis. Given the recent initiation of AZA, absence of gallstones, and characteristic imaging and lab findings, she was diagnosed with azathioprine-induced acute pancreatitis. She improved with supportive care. Lipase downtrended to 427, and she tolerated oral intake. On follow-up, mycophenolate mofetil 500 mg BID was initiated. Discussion: First-line treatment for AIH consists of prednisone alone or combined with azathioprine. However, for non-cirrhotic patients or those with mild disease, budesonide with AZA is also an accepted first-line regimen. Acute pancreatitis is rarely observed when AZA is used for autoimmune conditions other than IBD. This is believed to be caused by genetic susceptibility and clinical management differences. Systemic corticosteroids may blunt the T-cell–mediated hypersensitivity cascade underlying AIP. In contrast, budesonide, which is more commonly used in IBD, has high first-pass metabolism and low systemic bioavailability, does not confer the same protection.