Epstein-Barr virus (EBV) related acute liver failure: a case series from the US Acute Liver Failure Study Group

Abstract

Purpose: Acute liver failure (ALF) is a rare clinical syndrome associated with a high case fatality rate. Asymptomatic primary infection with Epstein-Barr virus (EBV) is common in the general population while acute hepatitis and jaundice are much less common and ALF has been rarely reported. We reviewed the presenting features as well as clinical outcomes amongst consecutive adults with EBV-related ALF.

Methods: Amongst the 1,887 adult ALF patients enrolled into the US ALF Study Group from January 1998 to February 2012, there were four patients (0.21 %) with EBV-related ALF. Diagnostic criteria for acute EBV infection included compatible serologies and/or the detection of EBV-encoded RNA (EBER) in liver tissue.

Results: Median patient age was 30 years (range 18-44); 75 % were male, and only 25 % were immunosuppressed. The median presenting ALT was 504 IU/mL (range 156-4,920), median Alk P was 431 (range 136-1,009), and median bilirubin was 17 mg/dL (range 13-22.1). Liver biopsy findings ranged from cholestasis to submassive necrosis with EBER + staining in two of the three samples tested. Although all of the patients were treated with an antiviral agent, two died of ALF, one underwent liver transplantation (LT) and one survived with supportive care and is well at 5 years. A review of the literature identified four additional LT recipients with favorable long-term outcomes.

Conclusion: Primary EBV infection accounts for <1 % of consecutive adult ALF cases but is associated with a high case fatality rate. LT is associated with favorable short- and long-term outcomes.

Figures

Fig. 1

Liver explant from patient #1, a 44-year-old female, with massive hepatic necrosis. The only hepatocytes in this field are the small collection to the right of center. The remainder of this field is collapsed parenchyma resulting from confluent lobular necrosis, with a portal tract at the lower left and proliferating bile ductules and neocholangioles to the left of center. (H&E stain, × 100 magnification)

Fig. 2

Liver biopsy from patient #4, an 18-year-old male with Crohn's ileocolitis on 6-mercaptopurine. The sinusoids are full of lymphocytes, a characteristic finding in EBV hepatitis. With EBER in situ hybridization staining, these sinusoidal lymphocytes stain positive for Epstein–Barr virus encoded RNA in blue (EBER stain, × 9200 magnification). The patient died of EBV-associated lymphoproliferative disorder