ReviewImmunoTargets and therapy2026
Distinct Clinical and Prognostic Features of Acute and Chronic Active Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis in Adults: A Scoping Review.
Review in ImmunoTargets and therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a major subtype of secondary HLH and is increasingly recognized as a heterogeneous entity. However, the clinical differences between acute EBV-HLH (AEBV-HLH) and chronic active EBV infection-associated HLH (CAEBV-HLH) have not been systematically characterized. We conducted a scoping review of PubMed up to December 7, 2024, and identified 168 eligible articles involving 714 adult patients with EBV-HLH, including 584 with AEBV-HLH and 130 with CAEBV-HLH. Epidemiologic features, clinical manifestations, treatment patterns, and prognostic factors were summarized and compared between the two subgroups. Patients with AEBV-HLH showed more severe HLH-related abnormalities, including lower blood counts and higher ferritin, triglyceride, lactate dehydrogenase, and plasma EBV-DNA levels, whereas central nervous system involvement was more frequent in CAEBV-HLH. The median overall survival was significantly longer in CAEBV-HLH (8.9 months) than AEBV-HLH (2.4 months, P=0.005). In the overall cohort, ferritin >5000 μg/L, soluble CD25 >10000 U/mL, EBV-DNA >10000 copies/mL, and receiving hematopoietic stem cell transplantation (HSCT) were independently associated with better overall survival. In subgroup analyses, soluble CD25, EBV-DNA, and HSCT remained independent predictors in AEBV-HLH, whereas undergoing HSCT was the only independent prognostic factor in CAEBV-HLH. These findings support distinct clinical and prognostic characteristics between AEBV-HLH and CAEBV-HLH, especially in adults. AEBV-HLH is characterized by a more fulminant inflammatory presentation, whereas CAEBV-HLH more often follows a chronic course with greater extensive organ. HSCT appears to be central to long-term outcome in both subtypes.
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