Liver regeneration after adult living donor and deceased donor split-liver transplants (2004)

The article by Humar et al. in the March 2004 issue of Liver Transplantation is interesting in its comparison of the degree of liver regeneration, as measured by computed tomography volumetry, between living donors, living donor right-lobe recipients and split-liver recipients.1 Their results show a significantly higher percentage increase in liver volume in left-lobe split-liver recipients (119.7%; P = .0006), in right-lobe split-liver recipients (113.6%; P = .01), and in right-lobe living donor recipients (103.9%; P = .0002) as compared to right-lobe living donors whose remnant liver volume had attained 78.6% of its ideal liver volume at 3 months postoperatively.1 In a rat model of partial liver graft transplantation, we recently published results showing an enhanced regenerative response associated with short (≤1 hr) periods of cold ischemia as evidenced by a significantly increased number of proliferating cell nuclear antigen and bromodeoxuridine stained hepatocytes in recipients of partial (30%) liver grafts as compared to control animals that underwent a 70% hepatectomy without transplantation.2 This effect was lost when the graft cold preservation time was prolonged to more than 10 hours and was at that point also associated with reduced survival. This finding seems to concord well with the results given in the article by Humar et al. in the split-liver group, where a relatively short cold ischemia, as in the left-lobe recipients, was associated with a higher regenerative response measured by computed tomography volumetry at 3 months.1 In the living donor recipients, however, the cold ischemia time seems inaccurate, as it is listed as 0 hours, which does not take into account the time required to at least flush the harvested hemiliver with cold preservation solution prior to implantation, and it seems to indicate that no back-table vascular reconstruction was undertaken in any of the cases studied. The presence of higher regeneration seen in the split-liver group as compared to the living donor recipients does, however, indicate that there may be an optimal cold ischemia time below or above which the triggering stimulus for hepatic regeneration is lost. The process of liver regeneration is complex and dependant on a multitude of factors, such as cytokine pathways, transcriptional regulation, and patterns of gene activation.3 In our model, a short period of cold ischemia was also associated with a higher production of interleukin 6 and tumor necrosis factor α compared to hepatectomy controls, and a prolonged cold ischemia (≥10 hr) resulted in a significant decrease in both proinflammatory cytokines with a significant reduction in the regenerative response.2 Administration of recombinant-interleukin- 6 reversed this negative effect of prolonged preservation and resulted in an improved regeneration with a significant increase in hepatocyte proliferating cell nuclear antigen staining when compared to animals that received partial liver transplants subjected to 10 hours of cold ischemia but without recombinant- interleukin-6 administration.2 Humar et al. looked at a number of clinical parameters shown to play a role in liver regeneration, including donor age, mean graft weight, and recipient graft-to-body-weight ratio.1, 3-5 It is difficult, however, to reach a definite conclusion on the impact of these various factors on hepatic regeneration, including cold ischemia time, in view of the small sample size studied in each group. More detailed clinical studies looking at both clinical and molecular factors will be required in the future as partial liver grafts continue to be used. The article by Humar et al. does provide interesting preliminary data, which should generate further work in this field. Zakiyah Kadry M.D.*, Nazia Selzner M.D. , Markus Selzner M.D. , Pierre-Alain Clavien M.D. Ph.D. , * Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, Department of Visceral & Transplantation Surgery, University Hospital Zurich, Switzerland Zurich, Switzerland.