Hepatitis E Virus Infection in a Liver Transplant Recipient Presenting With Late‐Onset Acute Rejection and Treated With Ribavirin

Hepatitis E virus (HEV) is increasingly recognized as a cause of allograft hepatitis in transplant recipients. Persistent HEV infection is often asymptomatic with nonspecific findings on liver biopsy, requiring high clinical awareness to order viral testing. We present a challenging case of HEV allograft hepatitis that presented with increasing liver enzymes and subtle biopsy findings of hepatocyte apoptosis and mitosis, diagnosed 1 month after treatment of acute rejection. Viral testing was positive for HEV IgM and HEV RNA, consistent with acute HEV infection. The patient was treated with a 12-week course of ribavirin. Based on this index case, we reviewed whether liver allograft biopsies with apoptosis were associated with viral detection at our institution during a 6-year period (<i>n</i> = 69) and compared histologic features of viral hepatitis and hepatitic patterns of rejection. Viral testing was performed in a majority (96%) of cases, but only five (7%) were tested for HEV. Anti-HEV IgG indicated prior exposure in one case. Clinicians should be aware there is histologic overlap between acute rejection and viral infection, including HEV, and etiologies may occasionally coexist. HEV testing should be considered in transplant recipients with unexplained elevated liver enzymes, particularly if biopsy demonstrates a hepatitic pattern or liver enzymes fail to normalize following treatment for rejection.