Elevation in Liver Transaminase (ALT-flares) in Transplant (TX) Recipients: Risk factors and Consequences
Background: ALT-flares are frequently observed in TX recipients, but the underlying reason is only known for a fraction. At our hospital, performing a large number of solid organ (SOT) and human stem cell TX's (HSCT), we initiated a program aimed at improving our understanding of the clinical implication from liver injury during post-TX follow-up (FU). Here we report on the incidence and risk factors for ALT flares, and the short- and long-term association with mortality.
Methods: Analysis included 1002 SOT (kidney (n=328), liver (170), lung (120), and heart (47)) and HSCT (337) recipients at our hospital, consecutive transplanted between Sept/09-July/13, and with prospective FU ≤ Oct/13. ALT-flares (>1.25xULN) were classified according to grade (NIH) and recognized cause (patient notes review). Poisson regression was used to determine incidence rate ratios (IRRs) of flares and death; generalized estimated equations allowed for repeated flares within individuals. Number and type of flare was included in models as time-updated variables.
Results: 501 of 1002 (50%) patients experienced a total of 1197 ALT-flares (46% had 1, 23% 2, and 31% >2 flares) during 1937 person years of FU (incidence 0.62 (95% CI 0.58-0.65)/PYFU). The reasons for the ALT flare was often unknown (50%), due to infections (12%), drug-induced (DILI-11%) or other reasons, and most were grade 2-3 (16% grade 4). Incidence of flares was elevated for all types of TX compared with kidney TX, was high in first 4-12 weeks postTX and plateaued thereafter for all except liver SOT (fig). During FU, 152 recipients died, and the adjusted IRR of death associated with experiencing 1, 2, or >2 (versus 0) ALT-flares were 1.1 (0.6-2.0), 2.1 (1.1-3.7), and 5.1 (3.2-8.1); the excess risk with >2 ALT flares persisted when lagging time between ALT flare and death by up to 6 months, for all types of ALT flares (p<0.05)(except DILI-associated), accounting for competing risk or excluding liver TX patients.
Conclusion: ALT flares occur frequently in the first 3 months after all types of TX, often remains unexplained, but if occurring several times is associated with excess risk of death 6 months thereafter. A better understanding of currently unrecognized factor contributing to ALT flares in this setting (e.g. HEV) is warranted.
A. Mocroft, None
J. Lundgren, None
F. Gustafsson, None
M. Iversen, None
N. Kirkby, None
A. Rasmussen, None
S. Schwartz Sørensen, None
L. Vindeløv, None
H. Sengeløv, None