Hemophagocytic Lymphohistiocytosis Directly Triggered by Peginterferon Alfa-2b in a Patient with Chronic Hepatitis B

Peipei Wang¹Jiahui Pang¹Huiming Xu¹Menglan Wang¹Wenxing Lai²Dayang Hui²Qingxian Cai^3*Xudong Li^2*Jianyun Zhu^1*

• ¹Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
• ²Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
• ³Shenzhen Third People's Hospital, Shenzhen, China

This case report describes a 42-year-old male with chronic hepatitis B (CHB) who developed hemophagocytic lymphohistiocytosis (HLH) following treatment with peginterferon alfa-2b (PegIFN-α-2b). The patient tolerated the initial injections well. After the 16th injection in February 2025, laboratory tests revealed cytopenia, prompting discontinuation of PegIFN-α-2b. The onset of a high-grade fever approximately three weeks after drug cessation coincided with the timeframe for the drug's clearance, suggesting a continued immunostimulatory effect. HLH was diagnosed based on hyperferritinemia (>50,000 ng/mL), elevated soluble interleukin-2 receptor (sCD25), and hemophagocytosis on bone marrow biopsy. He responded well to etoposide and dexamethasone. However, his course was complicated by sequential opportunistic infections: severe anemia due to parvovirus B19 (confirmed by plasma metagenomic next-generation sequencing, mNGS) and subsequent herpes simplex virus (HSV) encephalitis (diagnosed via CSF mNGS). Both complications were managed successfully with intravenous immunoglobulin and acyclovir, respectively. This case highlights PegIFN-α-2b as a rare direct trigger of HLH in CHB and underscores the critical risk of opportunistic infections during immunosuppressive therapy, demonstrating the pivotal role of mNGS in diagnosing elusive infections in immunocompromised hosts.