title: Cryptic Hepatitis B and E in Patients With Acute Hepatitis of Unknown Etiology.
abstract: BACKGROUND
  Up to 30% of acute viral hepatitis has no known etiology. To determine the disease etiology in patients with acute hepatitis of unknown etiology (HUE), serum specimens were obtained from 38 patients residing in the United Kingdom and Vietnam and from 26 healthy US blood donors. All specimens tested negative for known viral infections causing hepatitis, using commercially available serological and nucleic acid assays.
  
  
  METHODS
  Specimens were processed by sequence-independent complementary DNA amplification and next-generation sequencing (NGS). Sufficient material for individual NGS libraries was obtained from 12 HUE cases and 26 blood donors; the remaining HUE cases were sequenced as a pool. Read mapping was done by targeted and de novo assembly.
  
  
  RESULTS
  Sequences from hepatitis B virus (HBV) were detected in 7 individuals with HUE (58.3%) and the pooled library, and hepatitis E virus (HEV) was detected in 2 individuals with HUE (16.7%) and the pooled library. Both HEV-positive cases were coinfected with HBV. HBV sequences belonged to genotypes A, D, or G, and HEV sequences belonged to genotype 3. No known hepatotropic viruses were detected in the tested normal human sera.
  
  
  CONCLUSIONS
  NGS-based detection of HBV and HEV infections is more sensitive than using commercially available assays. HBV and HEV may be cryptically associated with HUE.
authors.affiliation: Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Lilia
authors.initials: L
authors.lastname: Ganova-Raeva
authors.affiliation: Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Lili
authors.initials: L
authors.lastname: Punkova
authors.affiliation: Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: David S
authors.initials: DS
authors.lastname: Campo
authors.affiliation: Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Zoya
authors.initials: Z
authors.lastname: Dimitrova
authors.affiliation: Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Pavel
authors.initials: P
authors.lastname: Skums
authors.affiliation: Vabiotech, Hanoi, Vietnam.
authors.forename: Nga H
authors.initials: NH
authors.lastname: Vu
authors.affiliation: Vabiotech, Hanoi, Vietnam.
authors.forename: Do T
authors.initials: do T
authors.lastname: Dat
authors.affiliation: Cornwall Gastrointestinal Unit, Royal Cornwall Hospital Trust and European Centre for the Environment and Human Health, University of Exeter Medical School, Truro, United Kingdom.
authors.forename: Harry R
authors.initials: HR
authors.lastname: Dalton
authors.affiliation: Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Yury
authors.initials: Y
authors.lastname: Khudyakov
mesh_terms: D000328:Adult; D000368:Aged; D001769:Blood / Q000821:virology*; D060085:Coinfection / Q000821:virology; D003955:Diagnostic Tests, Routine / Q000379:methods*; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification*; D016752:Hepatitis E virus / Q000235:genetics / Q000302:isolation & purification*; D006525:Hepatitis, Viral, Human / Q000175:diagnosis* / Q000209:etiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA; D006113:United Kingdom; D014481:United States; D014744:Vietnam; D055815:Young Adult
keywords: hepatitis of unknown etiology; liver diseases; next generation sequencing; shotgun library