Case Report: A Case of Epstein-Barr Virus-Associated Acute Liver Failure Requiring Hematopoietic Cell Transplantation After Emergent Liver Transplantation

Abstract

Hepatic manifestations of Epstein-Barr virus (EBV) infection are relatively common, mild, and self-limiting. Although fulminant hepatic failure has been reported in a few cases, the contributing factors are unclear. This report discusses a pediatric case of EBV-associated acute liver failure that required urgent liver transplantation; however, liver damage continued to progress post-liver replacement. Monoclonal CD8+ T cells that preferentially infiltrated the native and transplanted liver were positive for EBV-encoded small RNA, suggesting a pathophysiology similar to that of EBV-associated hemophagocytic lymphohistiocytosis and chronic active EBV infection. Therefore, subsequent chemotherapy and hematopoietic cell transplantation was conducted, which led to cure. This is the first case of EBV-associated acute liver failure that relapsed post-liver transplant. As such, it sheds light on an under-recognized clinical entity: liver-restricted hyperinflammation caused by EBV-infected monoclonal CD8+ T cells. This phenomenon needs to be recognized and differentiated from hepatitis/hepatic failure caused by EBV-infected B cells, which has a relatively benign clinical course.

Epstein Barr Virus-Related Acute Liver Failure and Hemophagocytosis in an Immunocompetent Individual: An Autopsy Report

“…3 EBV-ALF can affect both immunocompetent and immunocompromised individuals and is fatal in the majority or requires liver transplantation. 3,4,[7][8][9] The index case depicted the uncommon occurrence of EBV-ALF in an immunocompetent individual with relevant clinical and detailed histopathological features at autopsy.…”

Secondary hemophagocytic lymphohistiocytosis in children (Review)

“…Transplant-related HLH. HLH has been described in the context o HSCT (171,172) and, more rarely, in kidney (124,165) and liver (173)(174)(175) transplant recipients. Post-transplant HLH (PT-HLH) might be triggered by a combination of tissue damage, immunosuppressive therapy (176), alloimmune response, residual malignancies or by infections (171).…”

Viral Hepatitis Necessitating Liver Transplantation in Children

“…18 There are very few studies reporting LT for EBVinduced ALF in children. [54][55][56] Nakazawa et al 56 summarizing the experience from a single center in Japan reported that 11% (5/44) of ALF over a period of 8 y in previously healthy and immunocompetent children was caused by EBV; 3 of the patients needed urgent LT. In the same report, authors reviewed the literature for the LT for EBV-induced ALF and compiled a total of 6 pediatric patients.…”