Cryptic Hepatitis B and E in Patients With Acute Hepatitis of Unknown Etiology

• Published in: The Journal of infectious diseases Vol. 212; no. 12; pp. 1962 - 1969
• Main Authors: Ganova-Raeva, Lilia, Puntava, Lili, Campo, David S., Dimitrova, Zoya, Skums, Pavel, Vu, Nga H., Dat, Do. T., Dalton, Harry R., Khudyakov, Yury
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 15-12-2015
• Subjects: Adult; Aged; Blood - virology; Coinfection - virology; Diagnostic Tests, Routine - methods; Female; Hepatitis B virus; Hepatitis B virus - genetics; Hepatitis B virus - isolation & purification; Hepatitis E virus; Hepatitis E virus - genetics; Hepatitis E virus - isolation & purification; Hepatitis, Viral, Human - diagnosis; Hepatitis, Viral, Human - etiology; Humans; Male; Middle Aged; Sensitivity and Specificity; Sequence Analysis, DNA; United Kingdom; United States; Vietnam; VIRUSES; Young Adult; ISEW, Vietnam; hepatitis of unknown etiology; shotgun library; liver diseases; next generation sequencing
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiv315

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 nextgeneration 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.