How important is donor age in liver transplantation?

Table 1 Studies that analyze impact of donor age on liver transplant outcomes

Ref.	Type of donor	Cut-off age	No. of patients	Outcomes
Adam et al[1]	Deceased donor	< 55 yr vs > 65 yr	80347	Higher graft survival with donors younger than 55 yr
Adam et al[2]	Deceased donor	Multiple age groups	41522	No differences in one-year survival
Cuervas-Mons et al[3]	Deceased donor	55 yr	18568	Lower graft 5-yr survival rate with older donors
Feng et al[10]	Deceased donor	60 yr	20023	Higher rate of graft failure with older donors
Reese et al[11]	Deceased donor	45 yr	14756	Higher rate of graft failure at 90 d after LT with older donors
Serrano et al[12]	Deceased donor	60 yr	149	Lower graft survival rate with older donors
Anderson et al[13]	Deceased donor	60 yr	741	No differences were observed
Alamo et al[14]	Deceased donor	70 yr	129	No differences were observed in selected recipients (non HCV, low MELD, younger than 60 yr)
Kim et al[15]	Deceased donor	65 yr	100	Donor age should not be an absolute contraindication
Han et al[16]	Living donor	55 yr	604	Higher mortality rate with older donors
Dayangac et al[17]	Living donor	50 yr	150	Higher rate of major complication with older donors
Ikegami et al[18]	Living donor	< 30 yr vs > 50 yr	34	Better graft function and regeneration rates with donors < 30 yr
Ikegami et al[19]	Living donor	50 yr	232	Higher rate of small for size syndrome with older donors
Iwamoto et al[20]	Living donor	50 yr	232	Worse survival and high bilirubin levels with older donors
Ono et al[21]	Living donor	< 30 yr vs > 50 yr	15	Lower regeneration rate a week after LT with older donors
Uchiyama et al[22]	Living donor	48 yr	321	Higher rate of small for size syndrome with older donors
Li et al[23]	Living donor	70 yr	129	No differences in recipient survival rate at 1, 3 and 5 yr
Wang et al[24]	Living donor	50 yr	159	No differences in recipient survival rate at 1, 3 and 5 yr

LT: Liver transplantations; HCV: Hepatitis C virus; MELD: Model for End-stage Liver Disease.

Table 2 Variables included in the most relevant survival scores

Model	Variables included	Ref.
DRI	D-age, donor height, DCD, split, race, COD, allocation, CIT	Feng et al[10]
ET-DRI	D-age, DCD, Partial/Split, GGT, allocation, rescue allocation	Braat et al[25]
SOFT	D-age, COD, donor creatinine, R-age, R-BMI, previous OLT, previous abdominal surgery, R-albumin, dialysis, UNOS status, MELD score, encephalopathy, PVT, ascites, portal bleed, life support, allocation, CIT	Rana et al[26]
D-MELD	D-age, MELD score	Halldorson et al[27]
BAR	MELD score, CIT, R-age, D-age, previous OLT, life support	Dutkowski et al[28]

COD: Cause of death; CIT: Cold ischemia time; DCD: Donation after cardiac death; DRI: Donor risk index; D-age: Donor age; ET-DRI: Eurotrasplant donor risk index; SOFT: Survival outcomes following liver transplantation; R-age: Recipient age; OLT: Orthotopic liver transplant; PVT: Portal vein thrombosis; D-MELD: Donor age Model for End-stage Liver Disease; BAR: Balance of risk.

Table 3 Review of cellular and molecular mechanisms suggested to be implicated in the loss of aged liver’s regenerative capacity

Mechanism	Ref.
Telomere shortening	Takubo et al[55]
	Aikata et al[56]
	Aini et al[57]
Transcriptional and post-transcriptional modifications	Timchenko[60]
	Wang et al[61]
Hepatocelullar response to growth factors	Schmucker[53]
	Wang et al[61]
Pseudo-capillarization	Furrer et al[62]
Decline of progenitor cell populations and changes in their niches	Ono et al[18]
	Yousef et al[64]
	Conboy et al[65]
	Wang et al[66]