Observational Study
Copyright ©2014 Baishideng Publishing Group Inc.
World J Gastroenterol. Jun 7, 2014; 20(21): 6638-6650
Published online Jun 7, 2014. doi: 10.3748/wjg.v20.i21.6638
Table 1 Demographic characteristics of recipients and grafts undergoing protocol liver biopsy at two and five years after living donor liver transplantation
PLB at two years after LDLT (n = 89)PLB at five years after LDLT (n = 55)
Recipient characteristics at LDLT
GenderMale 37, female 52Male 20, female 35
Age (mo)22 (0-234)19 (7-198)
Body weight (kg)10.7 (2.6-58.5)9.7 (5.9-64.9)
Original diseaseBA 63, OTCD 9, AS 4, FHF 4, CEPS 3, graft failure 2, WD 1, PSC 1, CPS1D 1, LC 1BA 43, OTCD 3, AS 2, WD 2, FHF 1, HB 1, CF 1, CEPS 1, graft failure 1
PELD or MELD7.4 (-9.7-39.4)8.6 (-8.9-39.4)
Operation time13 h 25 min (7 h 33 min-30 h 28 min)17h 19 min (11 h 11 min-30 h 28 min)
Cold ischemic time2 h 17 min (36 min-8 h 6 min)2 h 06 min (25 min-16 h 19 min)
Warm ischemic time45 min (30 min-2 h 2 min)1 h 00 min (30 min-4 h 27 min)
Blood loss volume (mL/kg)77.0 (3.1-585.1)45.5 (6.7-776.2)
Transfusion volume (mL/kg)91.3 (0.0-597.7)68.1 (0.0-670.7)
Donor and graft characteristics at LDLT
GenderFather; 45, mother; 44Father; 30, mother; 25
Age (yr)33 (23-57)33 (23-53)
ABO compatibilityIdentical; 55, compatible; 20, incompatible 14Identical; 40, compatible; 8, incompatible 7
GV/SLV (%)68.0 (33.0-120.9)75.8 (35.7-121.2)
Graft typeLateral segment; 57, left lobe; 23,Lateral segment; 43, left lobe; 10,
S2 monosegment; 5, left lobe + caudate; 4left lobe + caudate; 2
Recipient and graft characteristics at PLB
Age (mo)48 (24-259)81 (68-257)
Body weight (kg)15.6 (7.3-64.6)21.4 (14.4-71.6)
Total bilirubin (mg/dL)0.63 (0.25-3.25)0.68 (0.26-2.55)
AST (IU/L)30 (14-61)27 (10-251)
ALT (IU/L)17 (9-54)17 (8-260)
γ-GTP (IU/L)17 (6-440)16 (9-510)
Hyaluronic acid (ng/mL)21 (9-239)17 (9-216)
IgG (mg/dL)927 (440-2063)1148 (475-2961)
GV/SLV (%)90.6 (70.2-126.9)93.0 (58.8-157.0)
Spleen volume (mL)125 (0-892)145 (0-692)
Trough of tacrolimus (ng/mL)3.4 (0-10.1)2.3 (0-15.5)
Table 2 Risk factors for ≥ A1 and ≥ F1 of protocol liver biopsy at two years after living donor liver transplantation: univariate analysis
VariablesIncidence of ≥ A1 (%)P valueIncidence of ≥ F1 (%)P value
Recipient age at LDLT
< 12 mo (n = 30) vs≥ 12 mo (n = 59)26.7 vs 23.70.76236.7 vs 18.60.062
Recipient body weight at LDLT
< 10 kg (n = 43) vs≥ 10 kg (n = 46)23.3 vs 26.10.75727.9 vs 21.70.500
Original disease
Cholestatic diseases (n = 69) vs others (n = 20)33.3 vs 38.10.63733.3 vs 38.10.637
PELD or MELD
≥ 20 (n = 22) vs < 20 (n = 67)22.7 vs 25.40.80331.8 vs 22.40.374
Donor age
≥ 35 yr (n = 39) vs < 35 yr (n = 50)23.1 vs 26.00.75125.6 vs 24.00.858
Gender combinations between donor and recipient
Mismatch (n = 50) vs match (n = 39)24.0 vs 25.60.85822.0 vs 28.20.501
ABO compatibility
Incompatible (n = 14) vs others (n = 75)21.4 vs 25.30.75514.3 vs 26.70.324
HLA-A
Mismatch (n = 65) vs match (n = 24)30.8 vs 8.30.02927.7 vs 16.70.285
HLA-B
Mismatch (n = 84) vs match (n = 5)26.2 vs 0.00.18725.0 vs 20.00.802
HLA-DRB1
Mismatch (n = 76) vs match (n = 13)26.3 vs 15.40.39826.3 vs 15.40.398
Lymphocyte cross-matching
≥ 4 × (n = 7) vs negative (n = 82)0.0 vs 26.80.11428.6 vs 24.40.805
GV/SLV
< 40 % (n = 6) vs≥ 40 % (n = 83)33.3 vs 24.10.61216.7 vs 25.30.636
Graft type
Lateral segment graft (n = 57) vs others (n = 32)21.1 vs 31.30.28529.8 vs 15.60.136
Operation time
≥ 20 h (n = 12) vs < 20 h (n = 77)16.7 vs 26.00.11325.0 vs 24.70.975
Cold ischemic time
≥ 2 h (n = 49) vs < 2 h (n = 40)32.7 vs 15.00.05528.6 vs 20.00.351
Warm ischemic time
≥ 45 min (n = 45) vs < 45 min (n = 44)20.0 vs 29.50.29726.7 vs 22.70.666
Blood loss volume
≥ 100 mL/kg (n = 30) vs < 100 mL/kg (n = 59)16.7 vs 28.80.20926.7 vs 23.70.762
Transfusion volume
≥ 100 mL/kg (n = 41) vs < 100 mL/kg (n = 48)22.0 vs 27.10.57622.0 vs 27.10.576
Splenectomy
Yes (n = 7) vs No (n = 82)42.9 vs 23.20.24728.6 vs 24.40.805
Portal vein complications
Yes (n = 11) vs No (n = 78)9.1 vs 26.90.19927.3 vs 24.40.834
Hepatic arterial complications
Yes (n = 6) vs No (n = 83)16.7 vs 25.30.63633.3 vs 24.10.509
Hepaticojejunostomic anastomotic stricture
Yes (n = 14) vs No (n = 75)21.4 vs 25.30.75528.6 vs 24.00.716
Cytomegalovirus infection
Yes (n = 29) vs No (n = 60)31.0 vs 21.70.33727.6 vs 23.30.663
Acute cellular rejection
Yes (n = 29) vs No (n = 60)10.3 vs 31.70.02917.2 vs 28.30.255
Total bilirubin at PLB
≥ 0.7 mg/dL (n = 29) vs < 0.7 mg/dL (n = 60)17.2 vs 28.30.25524.1 vs 25.00.929
AST at PLB
≥ 30 IU/L (n = 49) vs < 30 IU/L (n = 40)24.5 vs 25.00.95634.7 vs 12.50.016
ALT at PLB
≥ 20 IU/L (n = 27) vs < 20 IU/L (n = 62)40.7 vs 17.70.02137.0 vs 19.40.075
γ-GTP at PLB
≥ 20 IU/L (n = 34) vs < 20 IU/L (n = 55)32.4 vs 20.00.18929.4 vs 21.80.420
Hyaluronic acid at PLB
≥ 20 ng/mL (n = 52) vs < 20 ng/mL (n = 37)32.7 vs 13.50.03923.1 vs 27.00.671
IgG at PLB
≥ 1200 mg/dL (n = 18) vs < 1200 mg/dL (n = 71)27.8 vs 23.90.73733.3 vs 22.50.343
ANA at PLB
≥ 20 × (n = 8) vs < 20 × (n = 81)12.5 vs 25.70.40112.5 vs 25.90.401
ASMA at PLB
≥ 20 × (n = 21) vs < 20 × (n = 68)23.8 vs 25.00.91328.6 vs 23.50.640
Trough of tacrolimus at PLB
≥ 3.0 ng/mL (n = 54) vs < 3.0 ng/mL (n = 32)125.9 vs 25.00.92424.1 vs 25.00.924
Table 3 Risk factors for ≥ A1 and ≥ F1 of protocol liver biopsy at two and five years after living donor liver transplantation: multivariate analysis
VariablesOR95%CIP value
Risk factors for ≥ A1 of PLB at two years after LDLT
HLA-A mismatch
Mismatch vs match0.460.145-1.4790.194
Cold ischemic time
≥ 2 h vs < 2 h4.151.164-14.7890.028
Acute cellular rejection
Yes vs No0.200.046-0.8780.033
ALT
≥ 20 IU/L vs < 20 IU/L4.641.409-15.3060.012
Hyaluronic acid
≥ 20 ng/mL vs < 20 ng/mL3.300.982-11.0760.054
Risk factors for ≥ F1 of PLB at two years after LDLT
Recipient age
< 1 yr vs≥ 1 yr1.540.506-4.7060.446
AST
≥ 30 IU/L vs < 30 IU/L2.680.775-9.2380.120
ALT
≥ 20 IU/L vs < 20 IU/L1.860.646-5.3350.251
Risk factors for ≥A1 of PLB at five years after LDLT
Cold ischemic time
≥ 2 h vs < 2 h2.940.778-11.1400.112
Acute cellular rejection
Yes vs No2.260.728-7.0350.158
Risk factor for ≥ F1 of PLB at five years after LDLT
Acute cellular rejection
Yes vs No2.750.876-8.6370.083
Table 4 Clinical and hitopathological findings of cases with ≥ A2 or ≥ F2 of protocol liver biopsy at two or five years after living donor liver transplantation
CaseOriginal diseaseAge at PLB/sexPrevious ACRPost-transplant complicationsIS at PLBTac trough at PLBALT/HA at PLBA/F at PLBIS at follow-up biopsyA/F at follow-up biopsy
PLB at two years after LDLT
1OTCD71/female--Tac (3.0)2.512/352/1Tac (1.0)/MMF (400)1/1
2OTCD164/female-BDSTac (2.0)/MMF (1000)5.234/132/1Tac (2.0)/MMF (1000)1/0
3OTCD44/male--Tac (0.8)/MMF (250)225/< 92/2Tac (0.8)/MMF (500)N.E.
PLB at five years after LDLT
4BA70/female+Bowel perforationTac (0.6)1.122/132/2Tac (2.0)/MMF (1000)0/0
5BA118/female--Tac (1.0)2.320/242/2Tac (2.0)/MMF (1000)1/0
6BA70/female+HAT/IHBDSTac (0.8)/MMF(500)3.632/281/2Tac (2.0)/MMF (500)1/1
7BA71/female-CMV-ITac (0.4)016/< 92/2Tac (1.6)N.E.
8FHF83/female--Tac (2.0)/MMF (500)2.226/< 91/2Tac (2.8)/MMF (500)N.E.
9BA77/female-CMV-ITac (0.4)2.614/292/3Tac (0.8)0/1
10BA84/female+Fungal infectionTac (0.4)2.126/112/2Tac (0.4),MMF (500)1/1
11BA89/male+PVSTac (1.6)/MP (4.0)/MMF (1500)2.212/172/2Tac (1.6)/MP (2.0)/MMF (1500)1/1
12BA174/male-BDSTac (3.0)2.316/201/2Tac (4.0)0/1
13BA69/female+CMV-ITac (1.6)2.818/< 91/2Tac (2.0)/MMF (1000)0/1
14BA84/male-HVSTac (2.0)/MP (1.0)/MMF (1000)5.612/231/2Tac (2.0)/MP (1.0)/MMF (1000)N.E.
Table 5 Risk factors for ≥ A1 and ≥ F1 of protocol liver biopsy at five years after living donor liver transplantation: univariable analysis
VariablesIncidence ofA1 (%)P-valueIncidence ofF1 (%)P-value
Recipient age at LDLT
< 12 mo (n = 18) vs≥ 12 mo (n = 37)38.9 vs 51.40.38538.9 vs 32.40.637
Recipient body weight at LDLT
< 10 kg (n = 29) vs≥ 10 kg (n = 26)41.4 vs 53.80.35555.0 vs 30.80.577
Original disease
Cholestatic diseases (n = 45) vs others (n = 10)46.7 vs 50.00.85035.6 vs 33.30.738
PELD or MELD
≥ 20 (n = 12) vs < 20 (n = 43)41.7 vs 48.80.66041.7 vs 52.60.558
Donor age
≥ 35 yr (n = 22) vs < 35 yr (n = 33)40.9 vs 51.50.44036.4 vs 33.30.816
Gender combinations between donor and recipient
Mismatch (n = 30) vs match (n = 25)53.3 vs 40.00.32440.0 vs 28.00.352
ABO compatibility
incompatible (n = 7) vs others (n = 48)42.9 vs 47.90.80228.6 vs 35.40.722
HLA-A
Mismatch (n = 41) vs match (n = 14)51.2 vs 35.70.31639.0 vs 21.40.232
HLA-B
Mismatch (n = 52) vs match (n = 3)48.1 vs 33.30.61932.7 vs 66.70.229
HLA-DRB1
Mismatch (n = 47) vs match (n = 8)51.1 vs 25.00.17236.2 vs 25.00.539
Lymphocyte cross-matching
≥ 4 × (n = 16) vs negative (n = 39)31.3 vs 53.80.12718.8 vs 41.00.115
GV/SLV
< 40 % (n = 2) vs≥ 40 % (n = 53)0.0 vs 49.10.1730.0 vs 35.80.295
Graft type
Lateral segment graft (n = 43) vs others (n = 12)51.2 vs 33.30.27439.5 vs 16.70.141
Operation time
≥ 20 h (n = 16) vs < 20 h (n = 39)37.5 vs 51.30.35231.3 vs 35.90.742
Cold ischemic time
≥ 2 h (n = 40) vs < 2 h (n = 15)55.0 vs 26.70.06140.0 vs 20.00.165
Warm ischemic time
≥ 1 h (n = 42) vs < 1 h (n = 13)42.9 vs 61.50.23831.0 vs 46.20.314
Blood loss volume
≥ 150 mL/kg (n = 11) vs < 150 mL/kg (n = 44)27.3 vs 52.30.13727.3 vs 36.40.57
Transfusion volume
≥ 100 mL/kg (n = 15) vs < 100 mL/kg (n = 40)40.0 vs 50.00.50840.0 vs 32.50.603
Splenectomy
Yes (n = 2) vs No (n = 53)100.0 vs 45.30.1280.0 vs 35.80.295
Portal vein complications
Yes (n = 9) vs No (n = 46)44.4 vs 47.80.85233.3 vs 34.80.933
Hepatic arterial complications
Yes (n = 4) vs No (n = 51)25.0 vs 49.00.35425.0 vs 35.30.677
Hepaticojejunostomic anastomotic stricture
Yes (n = 16) vs No (n = 39)31.3 vs 53.80.12725.0 vs 38.50.340
Cytomegalovirus infection
Yes (n = 17) vs No (n = 38)47.1 vs 47.40.99947.1 vs 28.90.192
Acute cellular rejection
Yes (n = 23) vs No (n = 32)60.9 vs 37.50.08747.8 vs 25.00.079
Total bilirubin at PLB
≥ 0.7 mg/dL (n = 25) vs < 0.7 mg/dL (n = 30)48.0 vs 46.70.92036.0 vs 33.30.836
AST at PLB
≥ 30 IU/L (n = 22) vs < 30 IU/L (n = 33)54.5 vs 42.40.37836.4 vs 33.30.816
ALT at PLB
≥ 20 IU/L (n = 21) vs < 20 IU/L (n = 34)57.1 vs 41.20.24928.6 vs 38.20.464
γ-GTP at PLB
≥ 20 IU/L (n = 20) vs < 20 IU/L (n = 35)45.0 vs 48.60.79930.0 vs 37.10.592
Hyaluronic acid at PLB
≥ 20 ng/mL (n = 22) vs < 20 ng/mL (n = 33)50.0 vs 45.50.74136.4 vs 33.30.816
IgG at PLB
≥ 1200 mg/dL (n = 24) vs < 1200 mg/dL (n = 31)54.2 vs 41.90.36841.7 vs 29.00.328
ANA at PLB
≥ 20 × (n = 14) vs < 20 × (n = 41)35.7 vs 51.20.31628.6 vs 36.60.586
ASMA at PLB
≥ 20 × (n = 10) vs < 20 × (n = 45)70.0 vs 42.20.11140.0 vs 33.30.688
Trough of tacrolimus at PLB
≥ 3.0 ng/mL (n = 19) vs < 3.0 ng/mL (n = 33)152.6 vs 42.40.47736.8 vs 33.30.797
Table 6 Clinical and histopathological findings of cases who performed protocol liver biopsy at both two and five years after living donor liver transplantation
CaseOriginal diseaseAge at LT/sexPrevious ACRPost-transplant complicationsIS at two years PLBTac trough at PLBALT/HA at PLBA/F at PLBIS at five years PLBTac trough at PLBALT/HA at PLBA/F at PLB
1OTCD46/female--Tac (3.0)2.512/352/1Tac (1.0)/MMF (400)0.511/521/1
11BA26/male+PVSTac (0.8)/MP (4.0)/MMF (500)3.220/110/1Tac (1.6)/MP (4.0)/MMF (1500)2.212/172/2
12BA114/male-BDSTac (2.0)2.614/211/0Tac (3.0)2.316/201/2
13BA10/female+CMV-ITac (0.4)3.819/110/0Tac (1.6)2.818/< 91/2
14BA30/male-HVSTac (1.2)5.318/291/1Tac (2.0)/MP (1.0)/MMF (1000)5.612/231/2
15BA120/female-BDSTac (1.5)/PSL (2.5)4.415/140/0Tac (4.0)7.017/< 90/0
16BA163/male M+BDS/CMV-ICsA (150)CsA 509/270/0CsA (150)/MMF (1000)CsA 83910200/1
17BA8/female+/OKT3PVS/CMV-ITac (0.8)/MP (0.5)2.430/360/0Tac (2.0)5.315/181/1
18BA12/male+-Tac (0.8)3.814/580/0Tac (0.8)0.28/201/1
19BA13/female+CMV-ITac (1.6)/MP (2.0)9.322/110/0Tac (1.4)/MP (3.0)/MMF (500)2.115/150/1
20AD19/female+CMV-ITac (0.8)/MMF (500)2.319/130/1Tac (2.4)/MMF (500)3.814/151/1
21WD112/male--Tac (4.0)1.316/160/0Tac (5.0)1.419/130/0
22BA170/female+BDSTac (2.0)6.317/160/1Tac (6.0)/MP (12)/MMF (2000)15.539/221/0
23BA33/F+HVSTac (1.0)/MP (2.0)/MMF (400)3.710/< 90/0Tac (1.5)/MMF (1000)5.441/191/0
24BA9/female-HATTac (0.6)0.314/240/0Tac (0.8)010/100/0
25BA28/female--Tac (0.4)2.818/< 90/0Tac (1.0)0.915/101/0
26BA9/female-IHBDSTac (0.4)2.123/< 90/1Tac (2.0)/MP (0.5)/MMF (500)5.341/191/1
27AD19/male--Tac (0.6)3.312/170/0Tac (2.0)/MMF (500)1.511/590/0
28BA45/female-BDSTac (1.2)3.613/150/0Tac (1.5)4.611/100/0
29BA9/female--Tac (0.4)0.911/170/0Tac (0.8)1.113/250/0
30CEPS37/male--Tac (2.0)/MP (2.5)/MMF (500)2.513/< 90/0Tac (2.0)/MP (1.5)/MMF (500)3.911/< 90/0