Clinical relevance of plasma virome dynamics in liver transplant recipients

EBioMedicine. 2020 Oct:60:103009. doi: 10.1016/j.ebiom.2020.103009. Epub 2020 Sep 24.

Abstract

Background: The role of the microbiome in liver transplantation (LT) outcome has received a growing interest in the past decades. In contrast to bacteria, the role of endogenous viral communities, known as the virome, is poorly described. Here, we applied a viral metagenomic approach to study the dynamic evolution of circulating viruses in the plasma of LT recipients and its effect on the clinical course of patients.

Methods: Patients chronically infected with hepatitis B virus (HBV) that received a LT due to endstage liver disease were included in this study. Longitudinal plasma samples were collected pre- and post-LT. Intact viral particles were isolated and sequenced on an Illumina HiSeq 2500 platform. Short read libraries were analysed with an in-house bioinformatics pipeline. Key endpoints were the dynamics of viral families and post-LT complications.

Findings: The initiation of immunosuppression induced a bloom of the Anelloviridae that dominated the post-LT plasma virome. A variety of post-LT complication were observed. Nephrotoxicity was reported in 38% of the patients and was associated with a high abundance of anelloviruses. Besides nephrotoxicity, 16 (67%) patients experienced flares of viral or bacterial infections in post-transplant follow-up. These flares were recognized by an increased burden of anelloviruses (p < 0.05). Interestingly, no mortality was observed in patients infected with human pegivirus.

Interpretation: These findings suggest a diagnostic potential for the Anelloviridae family in post-LT complications. Furthermore, the impact of human pegivirus infection on post-transplant survival should be further investigated.

Funding: This trial was supported by Gilead Sciences grant number BE-2017-000133.

Keywords: Anellovirus; Liver transplantation; Metagenomic; Plasma; Transfusion; Virome.

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Coinfection
  • Computational Biology / methods
  • Female
  • Humans
  • Liver Transplantation / adverse effects*
  • Liver Transplantation / methods
  • Male
  • Metagenome
  • Metagenomics / methods
  • Middle Aged
  • Phylogeny
  • Transplant Recipients*
  • Viremia / diagnosis
  • Viremia / etiology*
  • Virome*
  • Virus Diseases / diagnosis
  • Virus Diseases / drug therapy
  • Virus Diseases / etiology*

Substances

  • Antiviral Agents