**Acknowledgements**

*Liver Disease and Surgery*

*3.2.1 RIPC in liver resections*

ischemia in the limb [75].

**4. Conclusion**

*3.2.2 RIPC in orthotopic liver transplantation*

In major HP, RIPC was shown to reduce liver I/R injury as indicated by a reduction in post-operative transaminases and increased ICG clearance [73]. To induce RIPC, a tourniquet was inflated to induce 10 min of ischemia and then deflated for 10 min to reperfuse the leg. This was repeated twice prior to commencing the operation. RIPC has potential to reduce liver injury following PH [73]. In addition, other clinical trial where RIPC was induced by three cycles of 5 min of ischemia of right upper limb followed by 5 min of reperfusion showed hepatic cytoprotective effects assessed by cholinesterase and bilirubin levels during liver resection [74]. Authors suggest that a shorter protocol of RIPC is safe and of equal effect, although

The first trial to investigate the feasibility of RIPC in liver transplant recipients was addressing by Robertson et al. [75]. The trial involved randomization of adult recipients undergoing deceased donor liver transplantation. To induce RIPC, a tourniquet was inflated for 5 min and then deflated for 5 min to reperfuse the leg. This was repeated twice and completed prior to the transplant procedure. Authors demonstrated that RIPC is feasible, acceptable to patients and safe in this group of patients but clinical benefits within the first 3 months post transplantation were not detected [75]. Authors suggest that 5 min cycles are insufficient to create localized

Surgical strategies such as the induction of IPC or RIPC could be of clinical interest in human liver resections and liver transplantation in both steatotic and non-steatotic livers. Both IPC and RIPC are easy to apply, inexpensive and does not require the use of drugs with potential side effects, but it requires a period of pre-ischemic manipulation for organ protection. These preconditioning techniques have been demonstrated to be promising tools for the reduction of hepatic I/R injury in different warm and cold ischemia models. Therefore, the potential applications of IPC and RIPC in human liver surgery are numerous. The benefits of IPC and RIPC have been evidenced in patients submitted to partial hepatectomy in both steatotic and non-steatotic livers. In our view, IPC and RIPC could resolve, at least partially, the lack of liver grafts available for transplant, since it can improve the post-operative outcome of liver grafts from extended criteria donors. However, controversial results on the effects of IPC and RIPC have been reported in the clinical practice of liver transplantation. It should be considered that the underlying mechanisms of both IPC and RIPC and their relevance in liver surgery remain poorly understood. Indeed, as stated along this chapter, most of the experimental studies have been focused on the molecular changes occurring during IPC and RIPC in non-brain-dead donors. Moreover, most of the experimental studies of IPC and RIPC have been performed only in I/R injury models, without hepatic resections or liver transplantation. The tolerance to I/R injury induced by either IPC or RIPC is dependently of the number of cycles of I/R and their duration as well as the surgical procedures. The clinical application of strategies designed at benchside will depend on the use of experimental models of IPC and RIPC that resemble as much as possible the clinical conditions. Multidisciplinary research groups should devote additional efforts to better understand the molecular mechanisms of IPC and RIPC

the mechanisms of this effect must be investigated in future studies [74].

**110**

This research was supported by the Ministerio de Economía y Competitividad (project grant SAF-2015-64857-R) Madrid, Spain; the European Union (FondosFeder, "una manera de hacer Europa"); by CERCA Program/Generalitat de Catalunya; by the Secretaria d'Universitats i Recerca (Grant 2017SGR-551) Barcelona, Spain. J Gracia-Sancho received continuous funding from the Instituto de Salud Carlos III (currently FIS PI17/00012) and the CIBEREHD, from Ministerio de Ciencia, Innovación y Universidades.
