S5746 ALTered Expectations: A Diagnostic and Therapeutic Detour into Silent Granulomatous Hepatitis

Introduction: Granulomatous hepatitis (GH) is a rare histologic diagnosis associated with a range of etiologies including drug reactions, infections, granulomatous disease, and autoimmune conditions. While systemic symptoms such as fever, malaise, and abdominal pain are associated with GH, some patients are asymptomatic with incidentally discovered abnormal liver enzymes (LEs), often attributed to metabolic dysfunction-associated steatohepatitis (MASH). We present a case of asymptomatic GH in a patient with persistently elevated LEs initially attributed to MASH. Liver biopsy revealed histologic features consistent with GH and treatment with azathioprine led to complete normalization of LEs. Case Description/Methods: A 53-year-old man with a history of hyperlipidemia, obesity, and prior alcohol use disorder was evaluated in hepatology clinic for asymptomatic chronically elevated LEs. Review of previous workup revealed a hepatocellular pattern of LEs: alanine aminotransferase 237 U/L, aspartate aminotransferase 147 U/L, alkaline phosphatase 67 U/L, and total bilirubin 0.5 mg/dL. Serologic testing ruled out alternative causes and right upper quadrant ultrasound showed mild hepatic steatosis. His elevated LEs were attributed to MASH and alcohol-related liver disease. However, despite mild weight loss and sustained alcohol abstinence, his LEs remained elevated. Subsequent liver biopsy revealed multiple non-necrotizing granulomas and chronic portal inflammation with <5% steatosis, no fibrosis, and negative bacterial and fungal stains. Tuberculosis and sarcoidosis testing was negative, and no medications were implicated. He was treated with steroids without improvement in his transaminitis. He was then started on azathioprine for steroid-refractory granulomatous hepatitis, resulting in normalization of his LEs after 3 months of therapy. Discussion: In this case, the patient’s lack of systemic symptoms, negative serologic workup, and isolated liver enzyme elevation posed a diagnostic challenge. This case highlights several key points. First, persistent transaminitis warrants a comprehensive evaluation, especially when noninvasive tests are inconclusive. Second, liver biopsy can uncover unexpected histologic diagnoses and has value in the era of noninvasive testing. Third, GH, though rare, should be considered after excluding other causes of liver disease. Lastly, therapeutic efficacy has been previously described using methotrexate and rituximab, but we successfully used azathioprine to achieve biochemical remission in this case of steroid-refractory GH.