Successful Management of HHV-8–Associated Primary Effusion Lymphoma and KICS in a Liver Transplant Recipient: A Case Report

Background

Human herpesvirus 8 (HHV-8), also known as Kaposi sarcoma-associated herpesvirus (KSHV), is an oncogenic virus responsible for several rare lymphoproliferative disorders. While its impact in HIV-positive individuals is well documented, data regarding its behavior and clinical consequences in solid organ transplant (SOT) recipients remain scarce. Primary effusion lymphoma (PEL) and KSHV inflammatory cytokine syndrome (KICS) are particularly rare and often fatal complications in this setting.

Case Report

A 56-year-old male underwent orthotopic liver transplantation (OLT) in February 2024 for alcoholic cirrhosis with refractory ascites, receiving a graft from a donor after circulatory death (DCD). Re-cipient HHV-8 serology was negative; donor serostatus was unknown. Immunosuppression included tacrolimus and steroids.In June 2024, the patient was admitted at our institution with fever, fatigue, jaundice, weight gain, and laboratory evidence of cholestasis, elevation of inflammatory markers, anemia, and hypo-natremia. Imaging (CT and MRI) revealed bilateral pulmonary infiltrates, ascites, and splenomegaly while biliary tract strictures were excluded. HHV-8 DNA was 32,156 copies/mL while EBV DNA was 739 cp/mL and CMV DNA was undetectable. A transjugular liver biopsy showed hemophago-cytic features; bone marrow biopsy ruled out HLH and lymphoproliferative disorders.Paracentesis revealed monoclonal plasmablasts positive for HHV-8 LANA-1, confirming a diagno-sis of PEL (Figure 1). The patient met criteria for KICS. Tacrolimus was discontinued and replaced with everolimus. Rituximab monotherapy resulted in rapid clinical improvement and decline in HHV-8 viremia. Chemotherapy was initiated with CVP, later escalated to R-CHOP (reduced-dose doxorubicin for persistent jaundice) due to worsening clinical status.Hospital stay was complicated by CMV reactivation and a catheter-related bloodstream infection due to Pseudomonas putida, both successfully treated. The patient completed 6 cycles of R-CHOP, with full-dose doxorubicin in cycles II and III due to hepatic function improvement. Dose reduction was later required due to febrile neutropenia and neurotoxicity.At 10-month post-transplant, PET-CT and contrast-enhanced CT confirmed complete remission. HHV-8 DNA remained undetectable. A liver biopsy performed in March 2025 for persistent choles-tasis revealed drug-induced liver injury (DILI) and nodular regenerative hyperplasia, likely chemo-therapy-related. As of June 2025, the patient remains in stable remission.

Discussion

PEL is a rare but potentially fatal post-transplant complication. Diagnosis is often delayed due to nonspecific clinical presentation and the need for invasive sampling. Literature on PEL in liver transplant recipients is limited to isolated case reports, with highly variable treatment approaches and outcomes. This case illustrates that early recognition, tailoring of immunosuppression, and timely initiation of targeted therapy—including rituximab and R-CHOP chemotherapy—can lead to sustained remis-sion even in the setting of PEL. Multidisciplinary management and careful monitoring are critical for optimizing outcomes in such rare and aggressive post-transplant lymphoproliferative disorders