Molecular Evidence of Patient‐to‐Patient Transmission of Hepatitis E Virus in a Hematology Ward

To the Editor—A 33-year-old man receiving treatment for acute leukemia in a hematological ward developed acute hepatitis (aspartate aminotransferase level, 1215 IU/L; alanine aminotransferase level, 2960 IU/L). Test results for viral markers (i.e., anti–hepatitis A virus IgM, hepatitis B virus surface antigen and DNA, anti–hepatitis C virus antibodies, and hepatitis C virus RNA) were negative; nonviral causes of liver disease, such as autoimmunity, toxic or iatrogenic hepatitis, and metabolic disorders, were excluded. A diagnosis of hepatitis E virus (HEV) infection was made after the detection of the HEV genome in plasma and stool samples from the patient [1]. Anti-HEV IgG was detected 2 weeks after the onset of the illness and persisted throughout. The patient had not traveled in areas where HEV was endemic and declared that he had had no contact with wild or domestic animals. He had not eaten raw meat or shellfish. No symptomatologic cases of hepatitis E had been reported in his family or in nurses and medical staff during the same period. The patient had received many transfusions from blood donors. Because HEV can be transmitted through transfusion [2], all donors' samples were tested and had negative results for HEV RNA. Medical records from the hematology ward indicated that a 44-year-old man with lymphoma had developed acute hepatitis E 1 year earlier. This patient was hospitalized repeatedly for short periods during that year until his lymphoma was cured. The patient did not recover after the acute phase of hepatitis, and he excreted HEV in both blood and stool for almost a year. His last stay in the ward overlapped with that of the other patient who was infected with HEV. We therefore looked for a link between the HEV strains from the 2 patients with use of samples that were collected at the time of diagnosis of acute hepatitis E. PCR products amplified from 3 distinct regions of the HEV genome were sequenced. Both strains belonged to HEV genotype 3f. Phylogenetic analyses including HEV sequences from local and GenBank reference strains indicated that the strains from the 2 patients were closely related. The nucleotide identity of the 3 HEV sequences from the 2 patients was 97.8%–98.6%. Both strains also harbored the same insertion in the ORF1 hypervariable region that differed from the reference sequences. Because the 2 patients lived 250 km apart in 2 geographically distinct areas and had not been exposed to a common source of HEV, transmission probably occurred during their overlapping stays in the hospital that occurred 3 weeks prior to the onset of hepatitis E in the patient with acute leukemia. A retrospective audit of the ward identified no major breaches of universal hygiene precautions. However, a lapse in strict hygiene procedures could be the cause of HEV contamination through enteric transmission, because HEV can persist for weeks on inanimate surfaces [3]. Parenteric iatrogenic transmission has also been suggested [4]. We conclude that universal hygiene precautions must be reinforced when cases of hepatitis E occur in medical wards where immunosuppressed patients are treated. There are several reasons for reinforced precautions: (1) immunosuppressed patients are highly susceptible to viral infections; (2) infected patients excrete HEV for a prolonged time, which results in a high risk of secondary transmission; (3) the virus persists for long periods on inanimate surfaces; and (4) no vaccine is available against HEV, although a phase-2 vaccine trial has had recent success [5]. Potential conflicts of interest. All authors: no conflicts.