Donor-specific cell-free DNA as a biomarker in liver transplantation: A review

Table 1 Publications examining donor-specific cell-free DNA in liver transplantation recipients (prior to census data of July 1^st, 2020)

Ref.	Year	Assay method	Genetic marker(s)	Study design and sample size	‘‘Healthy’’ threshold	Diagnostic accuracy
Lo et al[53]	1998	PCR and gel electrophoresis	Y chromosome	Prospective, cross-sectional (n = 8)	-	-
Beck et al[66]	2013	ddPCR(probe-based)	SNP	Prospective, cross-sectional (n = 10) and longitudinal (n = 7)	10%	-
Macher et al[68]	2014	qPCR(probe-based)	Y chromosome	Prospective, longitudinal (n = 10)	150 ng/mL	-
Macher et al[54]	2016	qPCR(probe-based)	Rhesus gene	Prospective, longitudinal (n = 17)	-	-
Kanzow et al[69]	2014	ddPCR(probe-based)	SNP	Retrospective, longitudinal (n = 1)	10%	-
Oellerich et al[70]	2014	ddPCR(probe-based)	SNP	Prospective, longitudinal (n = 10)	10%	-
Schütz et al[71]	2017	ddPCR(probe-based)	SNP	Prospective, longitudinal (n = 115)	10%	AUC for BPAR 0.97
Goh et al[79]	2017	ddPCR(probe-free)	DIP	Prospective, longitudinal (n = 3)	-	-
Ng et al[80]	2018	NGS(targeted)	Y chromosome	Prospective, longitudinal (n = 2)	0.1	-
Goh et al[78]	2019	ddPCR(probe-free)	DIP	Prospective, longitudinal (n = 20) and cross-sectional (n = 20)	898 copies/mL	AUC for tBPAR 0.97
Ng et al[81]	2019	qPCR(probe-free)	SNP	Prospective, longitudinal (n = 2)	0.1	-
Ng et al[82]	2019	NGS(targeted) and automated electrophoresis	Y chromosome, DNA fragments < 145 bp	Prospective, longitudinal (n = 11)	0.1, 0.6 (S/L fragments)	-

PCR: Polymerase chain reaction; ddPCR: Droplet digital PCR; SNP: Single nucleotide polymorphism; qPCR: Quantitative PCR; DIP: Deletion insertion polymorphism; BPAR: Biopsy-proven acute rejection; tBPAR: Treated BPAR with rejection activity index > 3; NGS: Next generation sequencing; bp: Base pairs; S/L fragments: Short to long fragment ratio; AUC: Area under the receiver operating characteristic curve.