Serum biomarkers and risk of hepatocellular carcinoma recurrence after liver transplantation

Table 3 Main studies analyzing several pre-liver transplantation systemic inflammation biomarkers and proposed scores

Reference	Country	LT type	n	Biomarkers	Time of biomarker test	Risk factors by multivariate analysis	Risk score
Yoshizumi et al[95], 2013	Japan	LDLT	104	AFP > 400, DCP > 300, NLR ≥ 4	Not specified	NLR, tumor size + number ≥ 8	No
Na et al[96], 2014	Korea	LDLT	224	AFP ≥ 100, NLR ≥ 6, CRP ≥ 1,	Day of LT	NLR ≥ 6 and AFP ≥ 100	Prognostic factor score: NLR ≥ 6 and CRP ≥ 1 (one point each)
Shindoh et al[80], 2014	Japan	LDLT	124	AFP, DCP, NLR	Day before LT, maximum and mean values within 90 d before LT	Tumor ≥ 5, MVI, mean NLR and maximum AFP and DCP before LT	Tokyo criteria, AFP > 250 and DCP > 450 (one point each)
Lai et al[78], 2014	Belgium	DDLT	146	AFP > 200, NLR > 5.4, PLR > 150	At inclusion on the waiting list, at LT,	AFP, NLR and PLR in univariate analysis	No
Parisi et al[79], 2014	UK	DDLT	150	NLR ≥ 5, PLR ≥ 150, IBI score	Day of LT	Absence of neoadjuvant therapy, beyond Milan criteria on explant	No
Harimoto et al[99], 2016	Japan	LDLT	190	DCP ≥ 300, NLR ≥ 2.66, PLR ≥ 70.4, CRP ≥ 0.27	Not specified	NLR, DCP, and tumor number ≥ 5	No
Wang et al[97], 2016	China	DDLT/LDLT	248	NLR continuous, AFP > 400	Within 1 wk before LT	NLR , AFP > 400, age, tumor number and size	Model TFS: 1.094 × tumor number (≤ 3, 0 points; > 3 (1 point) + 0.094 × maximum tumor diameter + 0.754 × AFP (≤ 400, 0 points; > 400, 1 point) + 0.085 × NLR -0.024 × age
Halazun et al[98], 2017	United States	DDLT/LDLT	339	NLR ≥ 5, AFP	NLR at day of LT; serial AFP at HCC diagnosis, before pre-LT treatment and at LT.	Tumor size and number, NLR ≥ 5, maximum pre-LT AFP, vascular invasion and poor differentiated tumors	MoRAL score: (1) pre-MoRAL: NLR ≥ 5 (6 points) + AFP > 200 (4 points) + largest tumor size > 3 cm by imaging (3 points); (2) post-MoRAL: grade IV tumors (6 points) + vascular invasion (2 points) + tumor size > 3 on pathology (3 points) + tumor number > 3 on pathology (2 points); and (3) combined score.
Fu et al[100], 2018	China	LDLT	150	NLR, PLR, MLR, SII	Within 1 wk before LT	No association	No

AFP: Alpha-fetoprotein; CRP: C-reactive protein; DCP: Des-gamma-carboxyprothrombin; DDLT: Deceased donor liver transplantation; IBI: Inflammation based index; LDLT: Living donor liver transplantation; LT: Liver transplantation; MVI: Microvascular invasion; NLR: Neutrophil-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio; SII: Systemic inflammation index; TFS: Tumor-free survival.