Transplant Trial Watch

Prevalence and impact of de novo DSA during a multicenter immunosuppression withdrawal trial in adult liver transplant recipients.

Jucaud V, Shaked A, et al.

Hepatology, 2018; [record in progress].


Aims
To determine whether early immunosuppression (IS) withdrawal affects development of de novo donor-specific antibodies (dnDSA), and whether dnDSA have an impact on liver transplant outcomes during IS minimization.

Interventions
Liver transplant recipients receiving calcineurin inhibitor monotherapy were randomized (4:1) to either IS minimization or IS maintenance.

Participants
40 stable liver transplant recipients (IS minimization, n=31; IS maintenance, n=9).

Outcomes
Presence and prevalence of de novo DSA. Impact of DSA on liver transplantation during IS minimisation or withdrawal assessed as association of de novo DSA with episodes of acute rejection (according to the Banff criteria).

Follow-up
Up to 1 year

CET Conclusions
Liver transplant recipients were randomised in a 4:1 ratio to immune suppression withdrawal or maintenance. The method of randomisation is not described and the trial was open-label, so unblinded. Whilst 57 patients were randomised, only 40 had complete follow up and it is unclear exactly why, when and how many dropped out from each arm. 31 patients were randomised to immune suppression withdrawal and completed follow up. Of these 31, 22 failed withdrawal due to acute rejection (59%), elevated liver tests (27%), graft dysfunction (5%), protocol deviation (5%) and PI decision (5%). Nine patients were kept immune suppression free; only 2 of these developed DSA during minimisation and a further 4 after withdrawal. Acute rejection episodes were strongly associated with DSA development and the majority of de novo DSA were against HLA-DQ antigens. This study demonstrates some evidence that de novo DSA positivity should be considered before immune suppression withdrawal in liver transplant recipients. Patients who were immune suppression-free subsequently had the highest prevalence of de novo DSA, particularly HLA-1, but these did not seem to be associated with adverse outcomes.

Jadad score
1

Data analysis
Per protocol analysis

Allocation concealment
No

Trial registration
None

Funding source
Non-industry funded