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.
A 68-year old male patient had been diagnosed with marginal zone lymphoma in 2011. He had received chemotherapy (R-CHOP) and autologous hematopoietic stem cell transplantation in 2012. After recurrence of his lymphoma in 2015 he had been treated with ibrutinib from 2015 to 2017 followed by bendamustine and RTX from January to October 2018. He had increased aminotransferases in March 2019, and HEV RNA was measured at 43 mio copies/mL in June 2019, prompting the initiation of treatment with ribavirin at a dose of 600 mg/d, which led to HEV clearance in July 2019. RBV treatment was terminated and the patient showed no HEV replication in October 2019. In November 2019, a viral relapse was detected and retreatment with 600 mg RBV/d was initiated.