Transmission of Hepatitis E Virus by Plasma Exchange: A Case Report

Background: Hepatitis E virus (HEV) is most often transmitted through the fecal–oral route in contaminated drinking water or food, but it can also be transmitted by blood and blood products (1). The virus usually causes an acute, self-limited illness with symptoms typical of other hepatitis viruses; however, fulminant disease is possible and chronic infection can occur in immunosuppressed persons.

Objective: To report transmission of HEV to a kidney transplant recipient through plasma exchange.

Case Report: Our patient was a 48-year-old North African woman with vascular nephropathy. After 3 years of hemodialysis, she received her first kidney transplant from a deceased donor on 23 August 2008. The patient's initial immunosuppressive regimen included a 5-day course of antithymocyte globulin; methylprednisolone, 1000 mg/d, rapidly tapered to prednisone, 10 mg/d; tacrolimus with a target trough concentration of 10 to 15 ng/mL; and mycophenolic acid, 1440 mg/d. Her long-term regimen included continuation of prednisone, tacrolimus, and mycophenolic acid. Acute humoral rejection was diagnosed 28 days after transplantation and was treated with a 3-day course of methylprednisolone, 500 mg/d; 6 rounds of plasma exchange; and 4 courses of intravenous immunoglobulins (2). Aminotransferase levels remained above the upper limit of normal for more than 15 months (Figure, top). Genome amplifications were negative for hepatitis B and C viruses, cytomegalovirus, herpes simplex virus, and Epstein–Barr virus. Test results for autoimmune and genetic liver diseases were negative, and liver ultrasound results were normal. Liver biopsy (25-mm specimen) showed extensive septal fibrosis (METAVIR fibrosis score F3). Nineteen months after transplantation, we detected HEV RNA genotype 3f (GenBank accession number KJ666642) in the patient's blood based on sequencing using open reading frame 1 (3), and she tested positive for anti-HEV IgG and negative for anti-HEV IgM. We confirmed that she had been infected for more than 1 year by finding HEV RNA in a frozen plasma sample drawn 5 months after transplantation. The kidney donor had tested negative for HEV RNA, and our patient's stored blood samples tested negative for HEV markers before transplantation. The patient reported never having consumed pork or shellfish, foods that have been implicated in HEV transmission, and she had lived in France, where fecal–oral transmission of HEV is rare, since transplantation. The method of transmission remained undetermined until we tested for HEV RNA in stored samples of all 18 blood products used during the peritransplantation period. From a single sample of fresh-frozen plasma, whose donor had tested negative on multiple occasions for hepatitis C virus, HIV-1 and -2, and hepatitis B virus before the plasma was used, we recovered a strain of HEV identical to the one infecting the patient (Figure, bottom), with a viral load of 7.5 _logIU/mL. This plasma had been used during a plasma exchange for treating acute humoral rejection. We prescribed ribavirin monotherapy (10 mg/kg for 68 weeks) without changing the immunosuppressive regimen, and the patient had a sustained virologic response.