The Risk Factors of Acute Cellular Rejection in Adult Living Donor Liver Transplantation: Doubting the Value of Positive Lymphocytotoxic Cross-match Results

Kyung Uk Jung; Jae Berm Park; Jong Man Kim; Ju Ik Moon; Gum O Jung; Jae Min Chun; Gyu-Seong Choi; Choon Hyuck David Kwon; Sung-Joo Kim; Jae-Won Joh; Suk-Koo Lee

doi:10.4285/jkstn.2009.23.3.237

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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

Original Article

J Korean Soc Transplant 2009;23(3):237-243.

Published online: 11 January 2009

DOI: https://doi.org/10.4285/jkstn.2009.23.3.237

The Risk Factors of Acute Cellular Rejection in Adult Living Donor Liver Transplantation: Doubting the Value of Positive Lymphocytotoxic Cross-match Results

Kyung Uk Jung, M.D., Jae Berm Park, M.D., Jong Man Kim, M.D., Ju Ik Moon, M.D., Gum O Jung, M.D., Jae Min Chun, M.D., Gyu-Seong Choi, M.D., Choon Hyuck David Kwon, M.D., Sung-Joo Kim, M.D., Jae-Won Joh, M.D., Suk-Koo Lee, M.D.

Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

책임저자：조재원, 서울시 강남구 일원동 50 성균관대학교 의과대학 외과학교실, 삼성서울병원, 135-701 Tel: 02-3410-3466, Fax: 02-3410-0040 E-mail: jw.joh@samsung.com

Received 30 July 20095 July 2009 Accepted 14 October 2009

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Keywords: Human leukocyte antigen, Lymphocytotoxic crossmatch, Acute rejection, Liver transplantation, Living donors

REFERENCES

1). Sugawara Y, Makuuchi M. Technical advances in living-related liver transplantation. J Hepatobiliary Pancreat Surg. 1999; 6:245–53.

2). Takiff H, Cook DJ, Himaya NS, Mickey MR, Terasaki PI. Dominant effect of histocompatibility on ten-year kidney transplant survival. Transplantation. 1988; 45:410–5.

3). Zmijewski CM. Human leukocyte antigen matching in renal transplantation: review and current status. J Surg Res. 1985; 38:66–87.

4). Banff schema for grading liver allograft rejection: an in-ternational consensus document. Hepatology. 1997; 25:658–63.

5). Gordon RD, Fung JJ, Markus B, Fox I, Iwatsuki S, Esquivel CO, et al. The antibody crossmatch in liver transplantation. Surgery. 1986; 100:705–15.

6). Suh KS, Kim SB, Chang SH, Kim SH, Minn KW, Park MH, et al. Significance of positive cytotoxic crossmatch in adult-to-adult living donor liver transplantation using small graft volume. Liver Transpl. 2002; 8:1109–13.

7). Kim YD, Lee SG, Hwang S, Park KM, Kim KH, Ahn CS, et al. Analysis of relationship between positive T lymphocytotoxic and/or B lymphcytotoxic crossmatch and acute rejection in adult-to-adult living donor liver transplantation. J Korean Soc Transplant. 2004; 18:183–7.

8). Demetris AJ, Markus BH. Immunopathology of liver transplantation. Crit Rev Immunol. 1989; 9:67–92.

9). Kerman RH. The role of crossmatching in organ transplantation. Arch Pathol Lab Med. 1991; 115:255–9.

10). Payne R, Rolfs MR. Fetomaternal leukocyte incompati-bility. J Clin Invest. 1958; 37:1756–63.

11). Van Rood JJ, Eernisse JG, Van Leeuwen A. Leucocyte antibodies in sera from pregnant women. Nature. 1958; 181:1735–6.

12). Brooks BK, Levy MF, Jennings LW, Abbasoglu O, Vodapally M, Goldstein RM, et al. Influence of donor and recipient gender on the outcome of liver transplantation. Transplantation. 1996; 62:1784–7.

13). Charco R, Vargas V, Balsells J, Lázaro JL, Murio E, Jaurrieta E, et al. Influence of anti-HLA antibodies and positive T-lymphocytotoxic crossmatch on survival and graft rejection in human liver transplantation. J Hepatol. 1996; 24:452–9.

14). Wiesner RH, Demetris AJ, Belle SH, Seaberg EC, Lake JR, Zetterman RK, et al. Acute hepatic allograft rejection: incidence, risk factors, and impact on outcome. Hepatology. 1998; 28:638–45.

15). Takakura K, Kiuchi T, Kasahara M, Uryuhara K, Uemoto S, Inomata Y, et al. Clinical implications of flow cytometry crossmatch with T or B cells in living donor liver transplantation. Clin Transplant. 2001; 15:309–16.

16). Takaya S, Bronsther O, Iwaki Y, Nakamura K, Abu- Elmagd K, Yagihashi A, et al. The adverse impact on liver transplantation of using positive cytotoxic crossmatch donors. Transplantation. 1992; 53:400–6.

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.

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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