In March 2013, a 62-year-old Bulgarian man was admitted with a provisional diagnosis of acute hepatitis based on a preexisting chronic HBV infection (inactive HBV carrier state: positive for HB surface antigen, core antibody, and envelope antibody; negative for HB envelope antigen and surface antibody with existing cirrhosis and ascites). One day prior to admission, the patient suffered from an acute onset of progressive, worsening upper abdominal discomfort, frequent episodes of diarrhea (2–3 times/day), loss of appetite, and fulminant jaundice without systemic symptoms. Laboratory results revealed elevated levels of aspartate aminotransferase (2,452 IU/L), ALT (1,161 IU/L), and GGT (301 IU/L), with high total bilirubin (392 μmol/L; direct bilirubin level: 345 μmol/L), and thrombocytopenia (119×106/L); C-reactive protein was markedly elevated (41.6 mg/L). HAV, HCV, and HIV were excluded. Serologic markers of previous CMV, EBV, and T. gondii infections were positive. Abdominal ultrasound showed known macronodular liver cirrhosis with manifest splenorenal shunting and splenomegaly. Anti-HEV IgM (165.9 IU/mL) and IgG (212.6 IU/mL) antibodies were positive. To exclude acute HBV-associated liver failure, polymerase chain reaction testing was performed using a commercially available kit (Abbott Laboratories, USA) to detect HBV-DNA (<12.5 IU/mL). HEV RNA was detected (9.76×105 copies/mL), and sequencing revealed HEV genotype 3f. Due to the severity of his condition, the patient was immediately transferred and underwent a high-urgency liver transplantation (CMV-positive transplant). The patient experienced the following complications: an ischemic cerebrovascular accident, acute renal failure, corticoid-induced diabetes mellitus, and CMV reactivation one month post-transplant (plasma viral load: 1,493 IU/L).\nIn September 2013, the patient died as a result of cardiac deterioration. A possible route of transmission could not be proven. However, there was a history of recent consumption of insufficiently heated pork sausage. Furthermore, the patient was at increased risk of developing severe complications due to the preexisting chronic liver disease.
In December 2009, a 32-year-old Caucasian woman was diagnosed with acute myeloid leukemia [t(11;19)]. She had no history of recent travel, contact with animals, or consumption of venison, liver sausage, or offal. She received a blood transfusion prior to undergoing consecutive cycles of chemotherapy. In February 2010, she underwent hematopoietic stem cell transplantation with cells obtained from her brother. A standard screening protocol performed prior to the transplantation showed she was seropositive for HSV, CMV, varicella zoster virus (VZV), EBV, and T. gondii. Further virologic investigation revealed vaccine-derived immunity to HBV, but no evidence of HAV, HCV, or HIV. One month post-transplantation, in March 2010, CMV reactivated and was treated with consecutive antiviral agents (valacyclovir, foscavir, ganciclovir, and cidofovir). In May 2010, pathologic laboratory values were obtained for alanine aminotransferase (ALT; 544 IU/L), aspartate aminotransferase (259 IU/L), and gamma-glutamyltransferase (GGT; 92 IU/L). Findings from an abdominal ultrasound were negative. She underwent a liver biopsy, with histologic findings compatible with acute viral hepatitis. In September 2010, she developed CMV-ventriculitis, which was confirmed by magnetic resonance imaging and presence of viral DNA in cerebrospinal fluid, and was successfully treated with ganciclovir plus cidofovir.\nLiver function tests remained abnormal, and in November 2010, a serum test for HEV RNA was conducted, revealing a high viral load (>5×106 copies/mL). Thus, a diagnosis of HEV infection (genotype 3f) was made, and the patient was treated with ribavirin monotherapy. Serologic HEV testing (RecomWell Hepatitis IgG/IgM; Mikrogen GmbH, Neuried, Germany) remained negative. Although no serum samples were available to evaluate pretransplant serostatus, the hematopoietic stem cell donor was HEV-seronegative. The HEV viraemia remained stable (5×106 copies/mL) for several months. In February 2011, Aspergillus pneumonia with pleural effusion appeared, without hepatic involvement, which was treated with caspofungin plus amphotericin B. One week later, the patient became extremely confused and suffered from dizziness and reduced consciousness. Examination of a plasma sample showed 2,565 copies/mL of adenovirus in addition to the persistent, high HEV viral load (5×106 copies/mL), and a sample of cerebral spinal fluid was positive for HEV RNA (3,700 copies/mL); CMV, adenovirus, EBV, and Toxoplasma were excluded.\nThe patient died in March 2011 due to multiple organ failure. Based on the chronic (>3 months), high-level detection of HEV RNA and no reported recent travel to endemic areas, an autochthonous, chronic HEV infection was most likely. An alternative origin of infection, such as the ingestion of contaminated food during the post-transplant period or transplantation of contaminated cells or blood products could not fully be excluded. Furthermore, no remaining stem cell preparation (prepared in an external laboratory) could be tested for the presence of HEV RNA.