| Objectives:To identify the relationship between the antibodies related HLA and ischemic cholangiopathy (IC) in the early stage after liver transplantation (LT) and explore the role of antibodies in the pathogenesis of IC.Experimental Design:As markers, antibodies related HLA, degradation product C4d and IC were observed in the patients who received cadaveric liver donor post-LT. Understand the expression of antibodies related HLA and DSA pre-existing or newly generated post-LT and analysis of the relationship between the antibodies and IC.Methods:Part Ⅰ:The liver samples were obtained from84ABO-compatible re-transplant patients with graft failure. Complement degradation product4d (C4d) was tested by immunohistochemistry. For the study analysis, the patients were divided into ischemic cholangiopathy group (n=50) and non-ischemic cholangiopathy group (n=31). According to time following first transplant, the patients were divided into within1month (n=9) and more than1month (n=75). The positive proportions of C4d were compared between different groups, respectively.Part Ⅱ:In the study,63patients were randomly selected from the recipients which received non-heart-beating donor graft and were followed up for3months at least. The anticoagulated whole blood specimens were collected before LT and3months post-LT respectively. HLA relating antibodies, DSA and MICA were detect by LABScreen (?) Single Antigen Detection and the occurrence of IC post-LT was recorded.Results:Part Ⅰ:Among84specimens, positive rate of C4d is62.29%(54/84). C4d mainly deposit in portal tract vasculature (portal veins, capillaries and hepatic arteries), portal tract stroma and sinusoids. There is no statistical difference between ischemic cholangiopathy group and non-ischemic cholangiopathy group (62%vs67.74%,P=0.17). Similarly, it is not different between ischemic cholangiopathy group and recurrent liver disease group (62%vs73.33%,P=0.18). Between within1month group and more than1month group, it is also no statistical difference (64%vs66.67%, P=0.28). Part Ⅱ:In total cases, the positive proportion of HLA antibody pre-existing was high for52.4%(33cases). The positive MICA was22.2%(14cases) and DSA was30.2%(19cases), respectively. In newly antibodies generated in the recipients after LT3months later, the positive proportion of HLA antibody is19.0%(12cases). The positive one of MICA is low with only4.8%(n=3). The onset time of IC post-LT are different between positive newly HLA-I antibodies group and negative group (P=0.011). Meanwhile, it is different between positive newly HLA antibodies group positive and negative one (P=0.022). In total pre-existing antibodies, only positive DSA shows higher IC incidence than negative DSA (P=0.011). The incidences of IC in the positive groups of newly antibodies are higher than the negative groups except MICA. Similarly, the positive proportions of these newly antibodies in the IC patients are significantly higher than in non-IC patients. Cox proportional hazard regression analysis finds it is the risk factor to IC post-LT that both the newly HLA-Ⅰ and HLA-Ⅱ antibodies are positive(P=0.029), with a relative risk of4.227(95%confidence interval is1.160-15.405). The proportion of secondary LT in positive newly HLA-I antibody group is higher than the negative group (P=0.024).Conclusions:As a marker of humoral response, C4d is common in failure liver grafts. Whether this humoral response is a normal physiological process between donor liver and recipient, or a pathological process result in graft failure need further research to investigate. IC post-LT is related to the antibodies newly generated in the receipients. However, the antibodies pre-existing has no effect on the incidence of IC except DSA. The incidences of IC in the positive groups of newly antibodies are higher than the negative groups except MICA. Similarly, the positive proportions of these newly antibodies in the IC patients are significantly higher than in non-IC patients. |
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