title: Use of serial assessment of disease severity and liver biopsy for indication for liver transplantation in pediatric Epstein-Barr virus-induced fulminant hepatic failure.
abstract: The decision to perform liver transplantation (LT) in patients with Epstein-Barr virus (EBV)-induced fulminant hepatic failure (FHF) relies on a precise assessment of laboratory and pathological findings. In this study, we analyzed clinical and laboratory data as well as the pathological features of the liver in order to evaluate the pathogenesis and the need for LT in 5 patients with EBV-induced FHF. According to the King's College criteria, the Acute Liver Failure Early Dynamic (ALFED) model, and the Japanese criteria (from the Acute Liver Failure Study Group of Japan), only 1 patient was considered to be a candidate for LT. However, explanted liver tissues in 3 cases exhibited massive hepatocellular necrosis together with diffuse CD8-positive T cell infiltration in both the portal area and the sinusoid. EBV was detected in the liver, plasma, and peripheral blood mononuclear cells (PBMNCs). In 2 cases indicated to be at moderate risk by the ALFED model, liver biopsy showed CD8-positive and EBV-encoded RNA signal-positive lymphocytic infiltration predominantly in the portal area, but massive hepatocellular necrosis was not observed. These patients were treated with immunosuppressants and etoposide under the diagnosis of EBV-induced hemophagocytic lymphohistiocytosis or systemic EBV-positive T cell lymphoproliferative disease of childhood. EBV DNA was detected at a high level in PBMNCs, although it was negative in plasma. On the basis of the pathological analysis of the explanted liver tissues, LT was proposed for the restoration of liver function and the removal of the EBV-infected lymphocytes concentrated in the liver. Detecting EBV DNA by a quantitative polymerase chain reaction in plasma and PBMNCs was informative. An accurate evaluation of the underlying pathogenesis is essential for developing a treatment strategy in patients with EBV-induced FHF.
authors.affiliation: Departments of Pathology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Nakazawa
authors.forename: Natsuko
authors.initials: N
authors.lastname: Nakano
authors.forename: Akinari
authors.initials: A
authors.lastname: Fukuda
authors.forename: Seisuke
authors.initials: S
authors.lastname: Sakamoto
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Imadome
authors.forename: Toyoichiro
authors.initials: T
authors.lastname: Kudo
authors.forename: Kentaro
authors.initials: K
authors.lastname: Matsuoka
authors.forename: Mureo
authors.initials: M
authors.lastname: Kasahara
mesh_terms: D000367:Age Factors; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000235:genetics; D003661:Decision Support Techniques; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000175:diagnosis / Q000821:virology; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007223:Infant; D008099:Liver / Q000473:pathology / Q000821:virology; D017114:Liver Failure, Acute / Q000175:diagnosis / Q000601:surgery* / Q000821:virology; D008111:Liver Function Tests; D016031:Liver Transplantation; D008214:Lymphocytes / Q000821:virology; D008297:Male; D018579:Patient Selection; D011237:Predictive Value of Tests; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D004279:DNA, Viral