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Interferon‐gamma blocking as a promising treatment for severe liver dysfunction in secondary hemophagocytic lymphohistiocytosis after liver transplantation

Year: 2025

Type: article

Abstract: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome that can occur after solid organ transplantation but remains underrecognized in this setting. The diagnosis is often delayed due to overlapping clinical manifestations with infection, rejection, or malignancy, and management becomes particularly challenging when accompanied by severe hepatic dysfunction. Here, we describe a pediatric patient who developed Epstein-Barr virus (EBV)-associated secondary HLH following liver re-transplantation for biliary atresia. On postoperative Day 10, the patient presented with high fever, cytopenia, hypertriglyceridemia, hypofibrinogenemia, and marked hyperferritinemia, accompanied by rapidly worsening liver injury. Bone marrow biopsy confirmed hemophagocytosis. Given the severe hepatic impairment and persistent inflammation, the patient received three doses of emapalumab (1 mg/kg), a monoclonal antibody blocking interferon-γ, combined with corticosteroids, intravenous immunoglobulin, and antimicrobial prophylaxis. The treatment led to a rapid decline in ferritin levels, reversal of liver dysfunction, and complete clinical recovery without opportunistic infections. The patient has remained stable with normal liver function and negative EBV DNA for over 2 years of follow-up. This case demonstrates that early interferon-γ blockade can safely and effectively reverse HLH-related liver injury after transplantation, offering a promising therapeutic strategy for the management of secondary HLH complicated by severe hepatic dysfunction.

Source: JPGN Reports

DOI: 10.1002/jpr3.70126