Viral Surveillance in Serum Samples from Patients with Acute Liver Failure by Metagenomic Next-Generation Sequencing

Sneha Somasekar, Deanna Lee, Jody Rule, Samia N. Naccache, Mars Stone, Michael P. Busch, Corron Sanders, William M. Lee, Charles Y. Chiu

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background Twelve percent of all acute liver failure (ALF) cases are of unknown origin, often termed indeterminate. A previously unrecognized hepatotropic virus has been suspected as a potential etiologic agent. Methods We compared the performance of metagenomic next-generation sequencing (mNGS) with confirmatory nucleic acid testing (NAT) to routine clinical diagnostic testing in detection of known or novel viruses associated with ALF. Serum samples from 204 adult ALF patients collected from 1998 to 2010 as part of a nationwide registry were analyzed. One hundred eighty-seven patients (92%) were classified as indeterminate, while the remaining 17 patients (8%) served as controls, with infections by either hepatitis A virus or hepatitis B virus (HBV), or a noninfectious cause for their ALF. Results Eight cases of infection from previously unrecognized viral pathogens were detected by mNGS (4 cases of herpes simplex virus type 1, including 1 case of coinfection with HBV, and 1 case each of HBV, parvovirus B19, cytomegalovirus, and human herpesvirus 7). Several missed dual or triple infections were also identified, and assembled viral genomes provided additional information on genotyping and drug resistance mutations. Importantly, no sequences corresponding to novel viruses were detected. Conclusions These results suggest that ALF patients should be screened for the presence of uncommon viruses and coinfections, and that most cases of indeterminate ALF in the United States do not appear to be caused by novel viral pathogens. In the future, mNGS testing may be useful for comprehensive diagnosis of viruses associated with ALF, or to exclude infectious etiologies.

Original languageEnglish (US)
Pages (from-to)1477-1485
Number of pages9
JournalClinical Infectious Diseases
Volume65
Issue number9
DOIs
StatePublished - Nov 1 2017

Fingerprint

Metagenomics
Acute Liver Failure
Serum
Viruses
Hepatitis B virus
Coinfection
Human Herpesvirus 7
Hepatitis A virus
Parvovirus
Viral Genome
Human Herpesvirus 1
Infection Control
Infection
Cytomegalovirus
Drug Resistance
Nucleic Acids
Registries
Mutation

Keywords

  • indeterminate ALF
  • metagenomic next-generation sequencing
  • pathogen discovery
  • SURPI computational pipeline
  • viral hepatitis

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Somasekar, S., Lee, D., Rule, J., Naccache, S. N., Stone, M., Busch, M. P., ... Chiu, C. Y. (2017). Viral Surveillance in Serum Samples from Patients with Acute Liver Failure by Metagenomic Next-Generation Sequencing. Clinical Infectious Diseases, 65(9), 1477-1485. https://doi.org/10.1093/cid/cix596

Viral Surveillance in Serum Samples from Patients with Acute Liver Failure by Metagenomic Next-Generation Sequencing. / Somasekar, Sneha; Lee, Deanna; Rule, Jody; Naccache, Samia N.; Stone, Mars; Busch, Michael P.; Sanders, Corron; Lee, William M.; Chiu, Charles Y.

In: Clinical Infectious Diseases, Vol. 65, No. 9, 01.11.2017, p. 1477-1485.

Research output: Contribution to journalArticle

Somasekar, S, Lee, D, Rule, J, Naccache, SN, Stone, M, Busch, MP, Sanders, C, Lee, WM & Chiu, CY 2017, 'Viral Surveillance in Serum Samples from Patients with Acute Liver Failure by Metagenomic Next-Generation Sequencing', Clinical Infectious Diseases, vol. 65, no. 9, pp. 1477-1485. https://doi.org/10.1093/cid/cix596
Somasekar, Sneha ; Lee, Deanna ; Rule, Jody ; Naccache, Samia N. ; Stone, Mars ; Busch, Michael P. ; Sanders, Corron ; Lee, William M. ; Chiu, Charles Y. / Viral Surveillance in Serum Samples from Patients with Acute Liver Failure by Metagenomic Next-Generation Sequencing. In: Clinical Infectious Diseases. 2017 ; Vol. 65, No. 9. pp. 1477-1485.
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