Human Herpesvirus 8 Causes a Wide Spectrum of Disease in Liver Transplant Recipients and May be Donor Derived: Case Series and Systematic Review of an Emerging Challenge.

BACKGROUND: Human herpesvirus 8 (HHV8), also known as Kaposi sarcoma (KS)-associated herpesvirus, can cause severe disease in liver transplant (LT) recipients, be donor-derived, and present variably. We describe HHV8 disease post-LT. METHODS: HHV8 disease was identified post-LT in New South Wales (NSW), 2017-2024, and from systematic review. Reports were compared by suspected donor-derived infection (DDI) and disease manifestation, using chi-square and t-tests. Survival was investigated with Cox proportional hazards. RESULTS: Of 188 records, 79 publications (131 cases) were included, plus four NSW cases (n = 135). Median onset was 7 months posttransplant (IQR: 5-13), with 33% suspected DDI. After median 12 months of follow-up, 68/125 had disease remission/regression; 59/135 died (49 HHV8-related). In NSW, Case 1 was proven DDI: visceral KS, 6 months post-LT; complete remission occurred with immunosuppression modification and chemotherapy. Case 2 was probable DDI: KS, multicentric Castleman's disease, and hemophagocytic lymphohistiocytosis, 3 months post-LT; the patient died despite immunosuppression modification, hydrocortisone and rituximab. Case 3 was possible DDI: KS-herpesvirus-induced cytokine syndrome, 6 months post-LT; died despite immunosuppression modification and ganciclovir. Case 4 was unlikely DDI: visceral KS, 5 months post-LT; complete remission occurred with surgery and immunosuppression modification. Survival was worse with visceral KS and non-KS disease (aHR 5.83 and 4.32, p = 0.002). Reduced immunosuppression, mTORi, and chemotherapy improved survival (aHRs 0.53, 0.36, 0.43; p = 0.006, 0.044, and 0.030). Treatment effects diverged by KS and non-KS disease. Donor screening identified more KICS and DDI, with improved non-KS disease survival. CONCLUSION: Post-LT HHV8 disease is heterogeneous, with high mortality. Targeted treatments and possibly donor screening improve survival.