*Purpose: Living donor liver transplant (LDLT) can sometimes be associated with impaired regeneration and severe ischemia/reperfusion (I/R) injury in the liver graft, resulting in small-for-size syndrome. Platelets are considered to act in concert with activated Kupffer cells (KCs) and leukocytes, which can be the core mechanisms for I/R injury. Recent studies highlighted platelets have strong effects on promoting liver regeneration. However, these studies are based on partial hepatectomized model, and the results in LDLT haven’t been thoroughly investigated. The aim of our study was to identify the role of platelets in liver graft regeneration and its outcomes after partial LT.

*Methods: We used a rat model of partial LT to mimic human LDLT. Firstly a 30% partial LT was performed. Recipient rats were treated with thrombopoietin before operation (TPO group), or given phosphate-buffered saline administration as control (control group). Postoperative parameters for regeneration and I/R injury were evaluated after transplantation. Both donors and recipients were administrated with clodronate liposome to deplete KCs (KDTPO group), changes in liver regeneration were analyzed. Secondly, a 20% partial LT was performed, and the effect of thrombocytosis on postoperative survival was evaluated.

*Results: The liver-to-body weight ratio was significantly higher post-LT in the TPO group compared with the control group. In western blot, the phosphorylation of Stat3, Nf-κB and CyclinD1 are increased in the TPO group. For I/R injury-related parameters, thrombocytosis didn’t aggravate the oxidative stresses and their down-stream pathways (Fig1). After KC depletion, platelet accumulation was significantly lower in the KDTPO group compared with the TPO groups, and platelet-induced increment of IL-6 and TNF-α were cancelled . Thrombocytosis improved postoperative survival in the TPO group (Fig 2).

*Conclusions: Our results suggested that thrombocytosis stimulated graft regeneration without aggregating I/R injury after partial LT, and Kupffer cells vitally contributed to platelet-derived regeneration. Platelet therapies to increase perioperative platelet counts may improve the outcomes after LDLT.

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