Manousou P, Arvaniti V, Tsochatzis E, Isgro G, Jones K, Shirling G, Dhillon A, O'Beirne J, Patch D, Burroughs A
Primary Biliary Cirrhosis after liver transplantation: influence of immunosuppression and HLA locus disparity. [JOURNAL ARTICLE]
Liver Transpl 2009 Oct 28.
Primary Biliary Cirrhosis(PBC) recipients despite excellent outcomes after liver transplantation(LT), may develop recurrent disease(rPBC). The impact of immunosuppression and HLA-mismatches in relation to rPBC is unclear. We evaluated 103 consecutive transplanted PBC patients(followed up>/=10 months) with serial protocol biopsies. Cox regression was used to evaluate factors associated with rPBC: MELD pre-LT, year of transplantation, age/gender of recipient/donor, cold/warm ischaemic time, HLA-mismatches, rejection, infections, immunosuppression(initial/maintainance). Mean follow up was 108(10-239)months, rPBC occurred in 36, mean 44(10-200)months. Inmmunosuppression was cyclosporine-based in 38(10 initial monotherapy), tacrolimus-based 62(19 initial monotherapy). Steroids discontinued in all but 7. Azathioprine was part of initial immunosuppression in 70, 26 discontinued, 33 never exposed. rPBC was associated independently with non use/discontinuation of azathioprine(p=0.015, HR 0.046, 95%CI 0.008-0.261). Mean time to rPBC was 74m with azathioprine, 43m when discontinued and 31m if no azathioprine was used. Cyclosporine or tacrolimus alone had no impact on rPBC, but cyclosporine with azathioprine was protective for rPBC compared to tacrolimus/azathioprine(0/18 versus 7/25 respectively, p=0.000). rPBC was not affected by HLA-mismatches. Azathioprine use in PBC transplanted patients is associated with less disease recurrence and longer time to rPBC. Tacrolimus or cyclosporine individually had no effect but cyclosporin and azathioprine combined, resulted in the least rPBC. Liver Transpl, 2009. (c) 2009 AASLD.
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