. 2022 Sep 3;33(1):e2393. doi: 10.1002/rmv.2393

TABLE 3.

Summary of evidence – rejection outcomes

Study	Cases/total	Outcome ^a	TTV timepoint	Exposure ^b	OR/HR ^c		Other findings
Blatter, ‘18	17/48 ^d	ACR	2wks post Tx	T, >median	0.16	(0.01–0.63) ^e	No association found at 6 weeks and 6 months post Tx.
Doberer, ‘19	11/37	BPR	2wks pre biopsy	C, 1	0.8	(0.64–1.00) ^f	Similar results in subanalyses without borderline lesions. Proposed threshold of 1.5*10^6 c/ml.
Doberer, ‘20	19/82	BPR	Day of biopsy	C, 1	0.91	(0.85–0.97)	Similar results for different subtypes of rejection.
Görzer, ‘17	20/47 ^g	CLAD	Day of CLAD	T, >7	0.12	(0.03–0.50) ^h	Proposed threshold of 7.0 log. Similar findings with the TTV‐load taken 50–20 days before CLAD, and lower a TTV‐load found during and before CLAD.
Schiemann, ‘17	46/715	ABMR	Day of rejection ⁱ	C, 1	0.91	(0.87–0.96) ^j	Similar results were found in subanalyses with patients subject to protocol biopsy.
Strassl, ‘19	33/113	BPR	±1.5 mo pre biopsy ^k	C, 1	0.90	(0.84–0.97)	Similar results using only the earliest biopsy. Proposed threshold of 6 log to detect rejection.
Fernández‐Ruiz, ‘19	11/221 ^l	AR	Before Tx	C, 1	0.69	(0.49–0.97)	Lower loads were found in patients with versus without outcome.
Jaksch, ‘18	11/143	ACR	3 month intervals	C, Min	0.48	(0.26–0.88) ^m	Similar results are shown for CLAD. A higher cumulative frequency of ACR is shown for TTV‐load <7.0 log in a 3 months window ⁿ .
Simonetta, ‘17	nd/29	BPAR	Before Tx	T, Pos	0.01	(0.001–0.092)^o	Unadjusted Kaplan Meier curve also showed a lower cumulative incidence of rejection in TTV positive at D0 patients.
Solis, ‘19	28/63 ^p	AMR	Before Tx	T, >3.4	0.14	(0.04–0.43) ^q	A similar result was found at M1, with a threshold of 4.2 log.
van Rijn, ‘21	88/389	AR	Time‐varying	C, 1	0.74	(0.71–0.76)	No other analyses are performed for rejection.
Blatter, ‘20	21/51	ACR	Before Tx, 1, 2, 3, and 5 wks (ratio) ^r	M		‐	No association between TTV‐load (ratios) and ACR or graft dysfunction.
Frye, ‘19	13/13 ^s	BPR	D0‐M1	T, x1/10 ^t		^u	A sensitivity and specificity of 0.74 and 0.99 is shown for detecting BPR ^s . Findings were similar for different outcome definitions.
Nordén, ‘17	nd/98 ^v	AR	Time‐varying (M3‐24)	C		^u	Analyses stratified on time (1–3, 3–6, 6–12 and 12–24 months post Tx) showed no association between the TTV‐load and the number of acute rejections.
Ruiz, ‘19	19/63 ^v	BPR	During rejection	M		‐	TTV‐load was similar patients with versus without BPR, and lower during clinical versus subclinical/no rejection, and moderate versus mild rejection.

Abbreviatopns: ACR, Acute cellular rejection; ABMR, antibody mediated rejection; AR, Acute rejection; BPAR, Biopsy proven acute rejectionc; BPR, biopsy proven rejection; CLAD, chronic allograft dysfunction; HR, hazard ratio; OR, odds ratio.

^{^a}

TTV exposure C: continuous, and step load increase in Log10. T: TTV load threshold, M: median or mean TTV load was compared in patients with and without outcome.

^{^b}

Number taken from figure.

^{^c}

Inverse of reported OR from supplement S2.

^{^d}

Adjusted for ATG as induction and previous SOT.

^{^e}

Total includes 27 controls.

^{^f}

Approximated from test accuracy numbers.

^{^g}

Median of 4.4 (ABMR+) and 6.6 (ABMR‐) yr after Tx.

^{^h}

Numbers from univariate analysis.

^ⁱ

Median of 127 d (105–174) post‐Tx.

^{^j}

Number reported in supplement S6.

^{^k}

Numbers reported in text, however the numbers reported in the table differ slightly.

^{^l}

Which 3 month window is used to determine the TTV‐load is not reported.

^{^m}

Adjusted for age, gender, HBV, HCV, HIV serostatus, underlying disease, number of immunosuppressive drugs used, hepatic encephalopathy, and presence of DSA's.

^ⁿ

A cohort composed of 50 BKV viruric patients +16 non BKV‐viremic patients, of which 63 had detectable TTV‐load, and 28 were BKV viremic.

^{^o}

Inverse of reported HR.

^{^p}

TTV‐load ratios were used as exposure.

^{^q}

The test accuracy is calculated on a biopsy proven rejection group.

^{^r}

Author definition of threshold: 10‐fold decrease of the individual TTV‐DNA levels within 1 month independently of the relative TTV‐DNA level.

^{^s}

No OR reported or numbers from which the OR can be approximated.

^{^t}

The number of patients with outcome is reported only per periodic interval.

^{^u}

ORs not reported.

^{^v}

19 patients with 20 episodes of rejection.