S5560 Common Variable Immunodeficiency-Associated Severe Acute Liver Injury

Introduction: Common variable immunodeficiency (CVID) affects 1–10 per 100,000 individuals globally with hepatic complications ranging from 5%–79% of cases. Common variable immunodeficiency related liver disease (CVID-rLD) often presents with features resembling autoimmune hepatitis (AIH) or primary biliary cholangitis (PBC) but lacks characteristic serological markers. We present a rare case of a patient with CVID who was found to have severe acute liver injury. Case Description/Methods: This is a 73-year-old woman with a history of CVID who presented to the hospital with jaundice and pruritis. Prior evaluation revealed fibrosis (FibroScan 6.8 kPa, F1). MRI in 2018 showed atrophy of the right hepatic lobe and hypertrophy of the caudate and left lobes along with splenomegaly. By 2023, her disease had advanced to stage 3-4 fibrosis. Liver biopsy in 2023 suggested primary biliary cholangitis (PBC). However, antimitochondrial antibodies, anti-gp210, and sp100 were within normal limits. A liver biopsy in 2025 instead suggested CVID-related liver disease. During her hospitalization, laboratory testing showed an alkaline phosphatase (ALP) increase from 203 IU/L (2017) to 470 IU/L (2025), total bilirubin increase from 1.1 mg/dL (2023) to 10.9 mg/dL (2025), and aspartate aminotransferase/alanine aminotransferase levels fluctuating from 51–160 IU/L, 11–73 IU/L respectively. She eventually improved with conservative management. On follow up 2 weeks later, she was again found to have worsening liver enzymes. She was started on Prednisone 40 mg daily only with minimal improvement. The plan was to discuss with her immunologist regarding starting a long-term immunosuppressant (possibly cellcept) and to continue Ursodiol 500 mg 3 times daily. Prednisone taper was also prescribed with a planned close follow up. Discussion: Patients with CVID who present with ALP >1.5 times the upper limit of normal or platelets <150 K/uL should be promptly referred to a hepatologist. CVID-rLD should be suspected in a patient with abnormal liver function tests, thrombocytopenia, and splenomegaly. Mortality in CVID-rLD doubles that of CVID patients without liver involvement (26.4% vs 11%). Nearly one-third of CVID patients with NRH have been found to have coexisting cirrhosis. Emerging therapies like Rituximab or anti-IL-6 agents warrant further exploration. The absence of standardized protocols for monitoring and treating CVID-rLD requires further research and guidelines. This case underscores the rarity of CVID-rLD resulting in severe acute liver injury but also the importance of early recognition and management of CVID-rLD.