TABLE 2.
Summary of evidence – infection outcomes
| Study | Cases/total | Outcome a | TTV timepoint | Exposure b | OR/HR c | Other findings | |
|---|---|---|---|---|---|---|---|
| Doberer, '19 | 127/274 | V/B/F | ±1 mo pre infection | C, 1 | 1.10 | (1.02–1.17) d | Similar for infections not requiring hospitalisation, BKV, CMV, opportunistic and extra cellular bacterial infections. |
| Görzer, '14 | 13/24 | V/B/F | 28–76 days pre infection e | T, >9.3 | 11.67 | (1.14–119.55) f | Case‐control study nested in a small cohort/case series. Peak TTV‐load in patients with infection were higher than in patients without. |
| Maggi, '18 | 99/235 | CMV viremia | D0‐10 post Tx | C, 1 | 1.5 | (1.0–2.3) g | Lower TTV‐load during 1‐year follow‐up in CMV DNA negative versus positive patients. Proposed threshold of 3.45 log to detect CMV reactivation. |
| Strassl, '18 | 31/72 h | V/B/F | 19–98 days pre infection | C, 1 | 1.23 | (1.04–1.45) | Proposed threshold of 3.1*10^9 c/ml to predict infection. Higher TTV‐levels in samples taken before (severe/bacterial) infection. |
| Uhl, '20 | 40/45 i | V/B/F | Time of infection | C, 1 | 1.016 | (0.876–1.180) | The authors also report no association in analyses with the TTV‐load taken 1 month before infection (OR: 1.075, CI: 0.921–1.25) and infection causing fever (OR: 0.932, CI:0.724–1.199). |
| Fernández‐Ruiz, '19 | 128/221 j | V/B/F/P | M1 post Tx | T, >3.15 | 2.88 | (1.13–7.36) k | Proposed threshold of 3.15 and 4.16 log for infection and immunity related adverse events. Cases did not have higher TTV‐load at D0 and D7, and higher loads at M1, 3 and 6. |
| Fernández‐Ruiz, '20 | 54/205 | BK viremia | M1 post Tx | T, >5.01 | 7.61 | (2.09–27.70) l | This study contains an additional analysis on the cohort described above, for BKV viremia as outcome. |
| Gore, '20 | 40/666 | V/B/F (death) | Hospital visit (1–20 yr post Tx) m | C, 1 | 1.26 | (1.07–1.48) | Analysis stratified on time found an association >2 years after Tx. Time to outcome was similar in no, low, medium and high TTV‐load groups. |
| Jaksch, '18 | 28/143 n | V/B/F | 3mo intervals | C, Max | 5.05 | (2.94–8.67) | The authors report a higher cumulative frequency of infection in patients with a maximum TTV‐level >9.5 log in a 3 months windowo. |
| Nordén, '17 | nd/98 p | V/B/F | Time‐varying (M3‐24) | C, 1 | 0.98 | (0.87–1.11) | Analyses stratified on time (1–3, 3–6, 6–12 and 12–24 months post LuTx) showed no association between TTV‐load and any infection. |
| van Rijn, '21 | 105/389 | BKV viremia | Time‐varying (M0‐12) | C, 1 | 1.03 | (1.03–1.04) | The authors report similar outcomes in the analysis with CMV viremia as outcome (HR 1.01,CI: 1.01–1.01). |
| Frye, '19 | 19/34 | V/B/F | D0, M2, 4, 6, 8, 10, 12 | M | ‐ | No difference in TTV‐load at D0 and M2, and higher TTV‐load in patients with infection at the other timepoints. | |
| Handala, '19 | 17/116 | BKV viremia | D0, M1, 2, 3 | M | ‐ | No difference in TTV‐load between patients with and without outcome at the timepoints. No correlation between TTV‐load and BKV DNA load at M3. | |
| Herrmann, '18 | 23/115 q | BKV viruria | Hospital visit, 0.6–34 yr post Tx | M | ‐ | In LiTx, they found a correlation between BKV DNA in urine and TTV DNA in serum, and higher TTV‐load in patients without BKV viruria than with. | |
| Ruiz, '19 | 41/63 | CMV viremia | During and pre infection | M | ‐ | Higher TTV‐load and cumulative TTV DNA during and before CMV infection and disease. No correlation between TTV‐load and CMV DNA during infection r . | |
| Solis, '19 | 28/63 s | BKV viremia | D0, M1, 3, 6, 12, 24 | C, 0.2 | t | No difference in TTV‐load at any timepoint between patients with and without BKV viremia during 2 year follow‐up, except at 6 months. | |
V: viral, B: bacterial, F: fungal, P: parasitic.
TTV exposure C: continuous, and step load increase in Log10. T: TTV load threshold, M: median or mean TTV load compared in patients with and without outcome.
OR: odds ratio, HR: hazard ratio.
Numbers from analysis with one event per patient.
Timing of TTV load sampling in control group is not reported.
OR not reported, approximated from reported test accuracy numbers. Large confidence interval due to very small groups.
It is unclear whether the reported OR is crude or adjusted for CMV prophylaxis, CMV negative serostatus and tacrolimus level at mo1.
Table 1 in the publication reports 22 with infection, the text reports 31 patients with infection and a total of 41 infections. In addition, the analysis allows for multiple outcomes per patient.
The analysis allowed for multiple infections per patient, 119 infectious episode occurred during the study period.
Sample size of the number of cases and total cohort. The sample size and number of cases at the month 1 timepoint is not reported.
Adjusted for delayed graft function and serum albumin at month 1.
Reported HR, adjusted for recipient age, hypertensive nephropathy and DCD donor.
Start of follow‐up time was set at hospital visit.
The authors allowed for multiple events per patients, events occurring within 1 mo were counted as 1 event.
Which 3 mo window is used to calculate the cumulative frequency is not reported.
The number of patients with outcome is reported only per periodic interval.
Only patients with detectable TTV loads were included (115/136).
The definition of cumulative DNA is not reported.
Cohort composed of 50 BKV viruric patients +16 non BKV‐viraemic patients, of which 63 had detectable TTV loads, and 28 were BKV viremic.
No OR reported or numbers from which the OR may be approximated.