Manifestaciones Hepáticas de Variantes de Ganancia de Función de STAT1

Primary immune regulatory disorders (PIRDs) are inborn errors of immunity characterized by immune dysregulation and multisystem involvement, whose hepatic manifestations can mimic autoimmune, cholestatic, or microvascular liver diseases. Among these, heterozygous Signal Transducer and Activator of Transcription 1 (STAT1) gain-of-function (GOF) pathogenic variants are predominantly associated with autoimmune hepatitis-like liver injury, while vascular and portal hypertensive phenotypes are rarely reported and likely under-recognized. We describe a young adult with recurrent infections and progressive liver disease ultimately diagnosed with a STAT1 GOF mutation. The case illustrates the spectrum of hepato-gastrointestinal involvement in PIRDs, emphasizing diagnostic considerations, imaging and histopathologic features, and management strategies including conventional immunosuppression, targeted Janus kinase (JAK) inhibition, and hematopoietic stem cell transplantation. We also outline infectious complications of JAK inhibition, including progressive multifocal leukoencephalopathy.