Journal List > J Korean Soc Transplant > v.23(3) > 1034295

Jung, Park, Kim, Moon, Jung, Chun, Choi, Kwon, Kim, Joh, and Lee: The Risk Factors of Acute Cellular Rejection in Adult Living Donor Liver Transplantation: Doubting the Value of Positive Lymphocytotoxic Cross-match Results

Abstract

Background:

The influence of lymphocytotoxic crossmatch results on acute cellular rejection in adult living donor liver transplantation (LDLT) has not been well examined. Therefore, in this study, we investigated the risk factors of acute rejection, including positive lymphocytotoxic crossmatch results.

Methods:

Patients inquired in this study are adults who underwent their first LDLT between June 1997 and June 2007 (n=382). We reviewed retrospectively the medical records of donors and recipients, including medical history, surgical procedures, and progress, then analyzed the risk factors of acute rejection using Cox’ s proportion hazard model.

Results:

Among the total subjects of 382, 32 recipients had positive lymphocytotoxic crossmatch results. Median follow-up duration was 28.0 months (range, 1∼93). Fifty six recipients had suffered at least one or more acute rejection episodes. In univariate analysis, positive lymphocytotoxic crossmatch results didn't turn out to be a significant risk factor of acute rejection (p=0.735), while recipient age (P=0.012), HCV-related (P=0.001), MELD score (P=0.042), gender mismatch (P=0.001) and no induction of anti-IL-2 receptor antibody (P=0.034) were revealed as risk factors for acute rejection. Recipient age (P=0.001, Hazard Ratio 0.937, 95% Confidence Interval 0.902∼0.973), gender mismatch (P=0.001, Hazard Ratio 2.970, 95% Confidence Interval 1.524∼5.788), HCV-related (P=0.001, Hazard Ratio 4.313, 95% Confidence Interval 1.786∼10.417) were considered as significant risk factors in multivariate analysis.

Conclusions:

Positive lymphocytotoxic crossmatch results may not be the risk factor for acute rejection. Therefore, it should not be considered as a determinant when matching donors with recipients in adult LDLT.

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Fig. 1.
Kaplan-Meier rejection-free survival curve of liver transplantations done in the negative (n=350) or positive (n=32) lymphocytotoxic crossmatch. There is no difference in the results (P=0.735). Abbreviation: LCCM, lymphocytotoxic crossmatch.
jkstn-23-237f1.tif
Table 1.
The characteristics of the living donor liver transplantation recipients (n=382)
Recipient factors  
 Age (years) 49.9±8.9
 Sex (M: F) 301:81
 Primary causes (cases)  
  HBV-related 314 (82.2%)
  HCV-related 24 (6.3%)
 Underlying HCC (cases) 175 (45.8%)
 MELD score 22.0±10.3
Donor factors  
 Age (years) 32.1±10.4
 Sex (M: F) 253:129
 Related donor: unrelated donor 273:109
 ABO (identical: compatible) 269:113
 HLA-DR mismatch (identical: half: different) 40:236:106
 LCCM (positive: negative) 32:250
  T-NIH 23:359
  T-AHG 22:360
  B cell 32:350
 Graft factors  
 Graft to recipient body weight ratio 1.167±0.275
Operative factors  
 Cold ischemic time (min) 79.8±47.5
 Warm ischemic time (min) 42.3±23.5
 Operation time (min) 603.7±110.6
Immunosuppression  
 Anti IL-2 receptor Ab induction (No: Yes) 81:311
Mean follow-up duration (months) 30.3±22.7

Abbreviations: LDLT, living donor liver transplantation; HCC, hepatocellular carcinoma; MELD, model for end-stage liver disease; HLA, human leukocyte antigen; LCCM, lymphocytotoxic cross- match.

Table 2.
Demographic findings and acute rejection rate in positive and negative crossmatches
Variables Positive (n=32) Negative (n=350) P
Recipient factors      
 Age (years) 52.3±7.8 48.7±9.0 0.024
 Sex (M: F) 13:19 288:62 <0.001
 HBV-related 25 (78.1%) 289 (82.6%) 0.529
 HCV-related 4 (12.5%) 20 (5.7%) 0.130
 Underlying HCC 12 (37.5%) 163 (46.6%) 0.324
 MELD score 24.5±11.0 21.7±10.3 0.146
Donor & Graft factors      
 Age (years) 30.0±10.9 32.3±10.4 0.223
 Sex (M: F) 19:13 234:116 0.392
 Gender Mismatch 22 (68.8%) 131 (37.4%) 0.001
 Unrelated donor 8 (25.0%) 101 (28.9%) 0.644
 ABO (compatible) 11 (34.4%) 102 (29.1%) 0.320
 HLA-DR mismatch 28 (87.5%) 314 (89.7%) 0.761
 GRWR 1.17±0.32 1.16±0.27 0.842
Operative factors      
 Cold ischemic time 85.8±48.4 79.3±47.5 0.473
 Warm ischemic time 38.2±23.6 42.7±23.5 0.316
 Operation time 612.6±138.2 602.2±107.8 0.610
Immunosuppression      
 Anti IL-2 receptor Ab 5:27 76:274 0.420
 induction (No: Yes)      
Mean follow up duration 30.1±21.0 30.3±22.9 0.971
Acute rejection 4 (12.5%) 52 (14.9%) 1.000

Abbreviations: LDLT, living donor liver transplantation; HCC, hepatocellular carcinoma; MELD, model for end-stage liver disease; HLA, human leukocyte antigen; GRWR, graft to recipient body weight ratio.

Table 3.
FK506 level in positive and negative crossmatches
FK506 level Positive (n=32) Negative (n=350) P
1 week after transplantation 10.6±5.1 9.9±4.7 0.445
2 weeks after transplantation 10.0±4.0 10.8±3.4 0.201
1 month after transplantation 9.3±3.0 8.8±3.6 0.527
Table 4.
Risk factors for acute rejection in living donor liver transplantation recipients in the univariate analysis
Variables P
Recipient factors  
 Recipient age 0.012
 Recipient sex 0.635
 HBV-related 0.137
 HCV-related 0.001
 Underlying HCC 0.165
 MELD score 0.042
 Donor & Graft factors  
 Donor age 0.596
 Donor sex 0.153
 Gender mismatch (Y/N) 0.001
 Related donor vs. unrelated donor 0.293
 ABO (Compatible/Identical) 0.631
 HLA-DR mismatch (Positive/Negative) 0.444
 LCCM (Positive/Negative) 0.735
 T-NIH 0.712
 T-AHG 0.785
 B cell 0.735
 Graft factor  
 GRWR 0.737
 Operative & Post operative factors  
 Graft type 0.917
 Cold ischemic time 0.098
 Warm ischemic time 0.905
 Operation time 0.995
 Immunosuppression  
 Anti IL-2 receptor Ab induction (N/Y) 0.034

Abbreviations: AR, acute rejection; LDLT, living donor liver transplantation; HCC, hepatocellular carcinoma; MELD, model for end-stage liver disease; HLA, human leukocyte antigen; LCCM, lymphocytotoxic crossmatch; GRWR, graft to recipient body weight ratio.

Table 5.
Risk factors for acute rejection in living donor liver transplantation recipients in the multivariate analysis
Variables P HR 95% CI
 Recipient age (years) 0.001 0.937 0.902∼0.973
 Gender mismatch (Y/N) 0.001 2.970 1.524∼5.788
 HCV-related (Y/N) 0.001 4.313 1.786∼10.417
 MELD score 0.114 0.969 0.932∼1.008
 Positive LCCM (Y/N) 0.808 1.301 0.155∼10.921
Abbreviations: HR, hazard ratio; CI, confidence interval; AR, acute rejection; LDLT, living donor liver transplantation; MELD, model for end-stage liver disease; LCCM, lymphocytotoxic crossmatch.
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