S5522 Beyond the Usual Suspects: Mixed Connective Tissue Disease-Related Cryoglobulinemic Necrotizing Hepatitis Without Viral Hepatitis

Introduction: Cryoglobulinemic necrotizing hepatitis (CNH) is a rare and potentially life-threatening cause of acute liver injury (ALI). Mixed cryoglobulinemia syndrome (MCS), often associated with hepatitis B or C, rarely presents with hepatic necrosis. We report a unique case of necrotizing hepatitis secondary to mixed cryoglobulinemia in the setting of mixed connective tissue disease (MCTD). Case Description/Methods: A 33-year-old woman with Raynaud’s phenomenon, hypertension, and obesity presented to an outside provider with fatigue and jaundice. Initial labs revealed elevated transaminases (aspartate aminotransferase [AST] 2078 U/L, alanine aminotransferase [ALT] 1,857 U/L) and total bilirubin of 15.2 mg/dL, prompting urgent referral to a liver transplant center. On arrival, labs revealed AST 552 U/L, ALT 896 U/L, total bilirubin 21.4 mg/dL, direct bilirubin 15.8 mg/dL, and international normalized ratio (INR) 1.87. Serologies and viral loads for Hepatitis A, B, and C were negative. Abdominal ultrasound showed a nodular liver contour concerning for cirrhosis. Liver biopsy revealed extensive necrosis (∼30%, portal and centrilobular), cholestasis, with sinusoidal congestion suggestive of systemic autoimmune-mediated and CNH (Type II cryoglobulins) associated ALI. Up to 40 IgG4+ plasma cells were noted per high power field. Autoimmune serologies showed a positive ANA (1:80), elevated RF (>360 IU/mL), and positive anti-RNP antibodies, consistent with MCTD. Although IgG4-related disease was considered, the clinical picture and hypergammaglobulinemia favored MCTD-associated cryoglobulinemia. Upon multidisciplinary review, the presentation was found to be most consistent with necrotizing hepatitis secondary to severe mixed cryoglobulinemia from MCTD. She was treated with rituximab, plasma exchange, and prednisone. At 2-month follow-up, labs improved to AST 166 U/L, ALT 166 U/L, total bilirubin 9.8 mg/dL, and INR 1.67; however, liver transplant evaluation was started due to the development of hepatic encephalopathy and an elevated Model for End-Stage Liver Disease 3.0. Discussion: This case highlights a rare presentation of cryoglobulinemic necrotizing hepatitis in the absence of hepatitis B and C. The underlying etiology of her MCS is attributed to be from her MCTD. While MCS can be linked to liver injury, it is unusual for patients to develop necrotizing hepatitis. Prompt recognition and early initiation of immunosuppression, including rituximab, plasma exchange, and steroids, is critical. This case highlights the importance of considering non-viral causes of cryoglobulinemia in ALI to facilitate timely diagnosis and therapy.