A 64-year old male with elevated aminotransferases presented himself at our outpatient clinic. He had been diagnosed with a monoclonal gammopathy of undetermined significance in 1992. In 2012, he had received eight cycles of bendamustine and RTX for Waldenstrom macroglobulinemia. Due to a relapse in 2016 he had been retreated with six cycles of bendamustine and RTX until February 2017, with stable remission since then. In November 2017, elevated aminotransferases were noted for the first time and the patient reported a short period of jaundice and fatigue. Extended laboratory testing revealed a HEV load of 6.1 E7 copies/mL. HEV IgG was positive and HEV IgM negative. After three months of persistent HEV replication, weight-based RBV treatment was started at a dose of 800 mg/d leading to virus clearance after three months of RBV treatment. RBV was stopped, but HEV relapsed only one month later and the patient was retreated with 800 mg RBV/d for an additional three months, achieving a sustained virological response.
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.