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Meta-Analysis
. 2023 Jan;33(1):e2393.
doi: 10.1002/rmv.2393. Epub 2022 Sep 3.

Torque teno virus load as marker of rejection and infection in solid organ transplantation - A systematic review and meta-analysis

A L van Rijn  1 , R Roos  2 , F W Dekker  3 , J I Rotmans  4 , McW Feltkamp  1
Affiliations
Meta-Analysis

Torque teno virus load as marker of rejection and infection in solid organ transplantation - A systematic review and meta-analysis

A L van Rijn et al. Rev Med Virol. 2023 Jan.

Abstract

Balancing immunosuppression to prevent rejection in solid organ transplant (SOT) recipients remains challenging. Torque teno virus (TTV), a commensal non-pathogenic virus, has been proposed as marker of functional immunity: higher loads correspond to over-immunosuppression, and lower loads to under-immunosuppression. This review offers an overview of the current evidence of the association between TTV-load and infection and rejection after SOT. A systematic literature search strategy, deposited in the PROSPERO registry, resulted in 548 records. After screening, 23 original and peer-reviewed articles were assessed investigating the association between TTV-load, infection and/or rejection in SOT. The Quality in Prognostic Studies (QUIPS)-tool was used to assess the risk of bias. Meta-analysis with random-effects was performed on results with similar outcomes and exposure measures. Most of the included studies involved retrospective cohorts in which the TTV-load was measured longitudinally, within the first 2 years post-transplantation. Infection outcomes differed between studies and included viral, bacterial, parasitic and fungal infections. Rejection was defined by biopsy confirmation or initiation of rejection treatment. Twelve out of 16 studies reported an association between high TTV-load and infections, whereas 13 out of 15 reported an association between low TTV-load and rejection. Meta-analysis showed an increased risk of infection (OR: 1.16, 95% CI: 1.03-1.32; HR: 1.05, 95% CI: 0.97-1.14) and a decreased risk of rejection (OR: 0.90, 95% CI: 0.87-0.94; HR: 0.74, 95% CI: 0.71-0.76) per 1 log TTV-load increase. The qualitative assessment showed varying risks of bias in the included studies. This systematic review and meta-analysis indicates that blood TTV-load measured within the first 2 years after SOT is associated with the risk of infection or allograft rejection, although substantial risk of bias in the studies included warrant cautious interpretation. The results in this review provide a rationale for larger, prospective, studies into TTV as marker of infection and rejection after SOT.

Keywords: TTV; biomarker; immunocompromised; solid organ transplantation.

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Conflict of interest statement

AL van Rijn, MCW Feltkamp and JI Rotmans are consortium partners of the EU‐funded TTV Guide Tx trial (https://cordis.europa.eu/project/id/896932) and will receive financial support as participating center, to carry out the trial. No funding was received for the preparation of this manuscript.

Figures

FIGURE 1
FIGURE 1
Graphical outline of TTV‐load as marker of infection and rejection
FIGURE 2
FIGURE 2
Flowchart of systematic literature search and screening
FIGURE 3
FIGURE 3
Risk of bias assessment. A total of 23 included studies were systematically assessed for publication bias over five domains listed on the left, with the help of the QUIPS tool
FIGURE 4
FIGURE 4
Meta‐analysis of the odds ratios (ORs) (black) and hazard ratios (HRs) (blue) for infection and rejection after solid organ transplant (SOT) associated with a TTV‐load increase on a continuous scale, per 1 log, for infection and rejection
See this image and copyright information in PMC

References

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