P. Donaldson et al., INFLUENCE OF HUMAN-LEUKOCYTE ANTIGEN MATCHING ON LIVER ALLOGRAFT SURVIVAL AND REJECTION - THE DUALISTIC EFFECT, Hepatology, 17(6), 1993, pp. 1008-1015
To date only one published large series of human leukocyte antigen mat
ching and liver allograft survival exists, and considerable confusion
has arisen about the advantage or disadvantage of human leukocyte anti
gen matching. In the present study we have reinvestigated the relation
ship between human leukocyte antigen mismatch and graft survival in 46
6 first liver allografts, seeking to clarify the relationship between
human leukocyte antigen and both acute rejection and the vanishing bil
e duct syndrome. In view of current criticism regarding the accuracy o
f serological tissue typing for human leukocyte antigen-DR, we have us
ed both classic serology and restriction fragment length polymorphism
analysis to ensure the accurate assignment of recipient DR types. In a
ddition, we have used polymerase chain reaction amplification and alle
le-specific and sequence-specific oligonucleotide probes to retest the
hypothesis that human leukocyte antigen class II matching may increas
e susceptibility to the vanishing bile duct syndrome. One-year graft s
urvival was significantly lower in patients with zero or two human leu
kocyte antigen-A mismatches (52% and 63%, respectively) than in those
with one human leukocyte antigen-A mismatch (69%) (p = 0.016 and p = 0
.018). A similar effect of B mismatching was observed, with a 1-yr gra
ft survival of 73% for those with one compared with 60% for those with
two human leukocyte antigen -B mismatches. In contrast no correlation
was found between DR mismatch and graft survival. Human leukocyte ant
igen class I matching appears to influence graft survival largely thro
ugh the occurrence of acute rejection and the development of the vanis
hing bile duct syndrome. In those patients who underwent liver biopsie
s, 49% (28 of 57) without acute rejection had a single B mismatch comp
ared with 32% (88 of 263) with acute rejection (chi2 = 5.5, p < 0.025)
. In addition, a complete human leukocyte antigen-A mismatch was more
common in those who developed the vanishing bile duct syndrome than in
those with normal graft function (54% vs. 38%; chi2 = 4.26, p < 0.05)
. In contrast to previous reports from this unit, no relationship betw
een human leukocyte antigen-DR or -DQ mismatch and the vanishing bile
duct syndrome could be detected. These findings indicate that human le
ukocyte antigen class I compatibility exerts a dual effect on the surv
ival of primary liver allografts. Although some human leukocyte antige
n-A and -B matching may be desirable for liver transplantation, full c
lass I matching may have an adverse effect.