The impact of late liver allograft dysfunction on physical activity of liver transplant recipients

Introduction. Liver transplantation restores patients' physical and social life, and its quality. The prevalence of low physical activity in liver recipients is unknown as well as the impact of late liver allograft dysfunction on it. Liver transplantation enhances patient's return to the usual physical and social activity and improves the quality of life. However, the prevalence of low physical activity among liver recipients and the impact of the late allograft dysfunction on it, which is a risk factor for obesity and cardiovascular diseases, require studying.The aim of the study was to identify whether the late liver allograft dysfunction influences the physical activity of recipients.Material and methods. The study included 87 liver recipients. We measured anthropometric parameters, physical performance (SPPB, LFI, 6-min walk test), mean step count per day. Late liver allograft dysfunction was determined if elevated transaminases and/or cholestatic enzymes or hepatic failure have been diagnosed later than 3 months posttransplant. Activity trackers were provided to assess physical activity.Results. Median age was 54 years [45;61], 33% were men. The median follow-up period was 36 months [16;64]. The median of the average steps count was 5.9 [4.1;8.7] thousand per day. 60.5% of recipients were sedentary and low active, 24.4% were somewhat active, 15.1% were active. In cases of liver allograft dysfunction, the mean step count was significantly lower than in patients with normal liver function: 4.1 thousand [2.6;5.3] versus 6.8 thousand [4.2;9.4], p=0.003, despite no differences in the physical activity test results.Conclusion. In case of a late liver allograft dysfunction, the physical activity can decrease; 60.5% of liver recipients, in the absence of pathological restriction of movement, have a sedentary and low active lifestyle. Activity trackers may allow identifying patients who need additional check-up or physical training.

Dendritic Cell-Mediated Regulation of Liver Ischemia-Reperfusion Injury and Liver Transplant Rejection

Liver allograft recipients are more likely to develop transplantation tolerance than those that receive other types of organ graft. Experimental studies suggest that immune cells and other non-parenchymal cells in the unique liver microenvironment play critical roles in promoting liver tolerogenicity. Of these, liver interstitial dendritic cells (DCs) are heterogeneous, innate immune cells that appear to play pivotal roles in the instigation, integration and regulation of inflammatory responses after liver transplantation. Interstitial liver DCs (recruited in situ or derived from circulating precursors) have been implicated in regulation of both ischemia/reperfusion injury (IRI) and anti-donor immunity. Thus, livers transplanted from mice constitutively lacking DCs into syngeneic, wild-type recipients, display increased tissue injury, indicating a protective role of liver-resident donor DCs against transplant IRI. Also, donor DC depletion before transplant prevents mouse spontaneous liver allograft tolerance across major histocompatibility complex (MHC) barriers. On the other hand, mouse liver graft-infiltrating host DCs that acquire donor MHC antigen via “cross-dressing”, regulate anti-donor T cell reactivity in association with exhaustion of graft-infiltrating T cells and promote allograft tolerance. In an early phase clinical trial, infusion of donor-derived regulatory DCs (DCreg) before living donor liver transplantation can induce alterations in host T cell populations that may be conducive to attenuation of anti-donor immune reactivity. We discuss the role of DCs in regulation of warm and liver transplant IRI and the induction of liver allograft tolerance. We also address design of cell therapies using DCreg to reduce the immunosuppressive drug burden and promote clinical liver allograft tolerance.