Impact of human leukocyte antigen mismatching on outcomes of living donor liver transplantation for primary biliary cirrhosis

Abstract

We read with great interest the recent article from the Kyoto group regarding primary biliary cirrhosis (PBC) patients after living donor liver transplantation (LDLT).1 Of 50 patients, 14 died within 6 months after LDLT, and 9 patients showed recurrence with a median follow-up duration of 36 months. The Kyoto group emphasized that the large number of patients with a human leukocyte antigen (HLA) mismatch was related to the poor survival and high recurrence rates. This finding, however, is in contrast to our experience. HLA, human leukocyte antigen; LDLT, living donor liver transplantation; MELD, model for end-stage liver disease; PBC, primary biliary cirrhosis; UMRS, updated Mayo risk score. From September 1997 to July 2006, 64 patients with PBC underwent LDLT procedures at the University of Tokyo Hospital. We have no exclusion criteria in LDLT for PBC in terms of preoperative conditions expressed by the updated Mayo risk score (UMRS)2 or model for end-stage liver disease (MELD) score.3 There were 9 men and 55 women with a median age of 52 years (range: 35-66 years). The median preoperative UMRS and MELD score were 10 (range: 6-14) and 14 (range: 2-39), respectively. The living donors consisted of 34 men and 30 women with a median age of 35 years (range: 20-66 years). There were 54 blood-relative donors (35 offspring, 14 siblings, 1 parent, 1 aunt, 1 cousin, 1 nephew, and 1 niece) and 10 non–blood-relative donors (10 spouses). The median follow-up period was 45 months (range: 0-109 months). Of the 7 patients that died after LDLT, 5 died within 6 months. The causes of death were pneumonia (n = 2), brain hemorrhage (n = 1), simultaneous thrombosis of the portal vein and hepatic artery (n = 1), and chronic rejection (n = 1). The remaining 2 patients died of pneumonia (n = 1) and virus-associated hemophagocytic syndrome (n = 1). The 1-year, 3-year, and 5-year patient survival rates were 92%, 90%, and 88%, respectively. A total of 84 biopsies were performed in 37 patients. Acute rejection was diagnosed in 24 patients. Biopsy specimens confirmed that there was no recurrence of PBC. The 5-year survival rate for patients receiving grafts from blood-relative donors (n = 54) was 87% and was not statistically different from that for patients receiving grafts from non–blood-relative donors (n = 10, 90%, P = 0.98). A univariate survival analysis revealed no statistical difference in other factors, including the UMRS, MELD score, donor age, and graft weight/standard liver volume ratio. Complete HLA typing information for both the recipient and donor was obtained from 60 patients. Of these, 6 patients died after LDLT. The survival rate was not affected by the number of HLA-type mismatches (Fig. 1). Survival rate stratified by the total number of mismatches in HLA-A, HLA-B, and HLA-DR loci. The cause of death should be determined to be immunologic or nonimmunologic when the impact of the positive graft on survival is considered. It is difficult to determine whether all of these deaths were associated with immunologic mechanisms because the causes of death in the Kyoto group's cohort were not explained in detail. Because the strategy of LDLT for patients with PBC in the Kyoto group is not so different from ours, its findings regarding the impact of HLA mismatching on the outcome of LDLT for PBC cannot be accepted as universal. Takuya Hashimoto*, Yasuhiko Sugawara*, * Masatoshi Makuuchi, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.