Hepatic reinnervation following orthotopic liver transplantation in man

Abstract

We have studied changes in the pattern of intrinsic hepatic innervation in sequential liver biopsies from 16 patients who underwent orthotopic liver transplantation. Seventy-one needle biopsies were used, including specimens obtained at the time of transplantation (time zero) and up to 4 years post-transplantation; five transplant hepatectomy tissue blocks removed 3-32 months after transplantation were also assessed. Paraffin sections were immunostained with anti-PGP 9.5 and anti-S-100 to identify nerve fibres. All 'time zero' biopsies contained portal nerves and all but two showed staining of parenchymal fibres. After 1 week, no subsequent biopsies contained parenchymal fibres. The disappearance of portal fibres was less rapid and showed greater variability between patients, but they had all disappeared by 6 weeks and there was no positive staining between 6 and 60 weeks. Thereafter, a minority of biopsies showed innervation of a few small portal tracts. Samples from the porta hepatis, hepatectomy specimens, and needle biopsies containing large tracts showed persistence of major nerve trunks at all stages. Abnormally large nerve bundles were seen in some of these areas. The pattern of nerve staining showed no obvious relationship to the intensity of rejection changes. Our results suggest that there is a limited, delayed capacity for regeneration of portal, but not parenchymal, fibres in the transplanted human liver. The physiological significance of this long-term parenchymal denervation in transplanted livers remains to be determined.

Regulation of glucose homeostasis in humans with denervated livers.

“…Therefore, in this study we explored the effect of liver denervation on hepatic glucose production and insulin-mediated glucose disposal in 22 liver transplant patients (in whom the liver was surgically denervated) in stable clinical conditions with a follow-up period of 28 mo. Studies designed to assess whether and to what extent sympathetic reinnervation occurs postoperatively in the transplanted human liver found a limited capacity for regeneration of portal but not parenchymal fibers (37,38). The physiological relevance of such delayed and scarce partial reinnervation is negligible.…”

Anatomy, pathophysiology and basic mechanisms of disease

“…293,294 Recent studies have made clear that hepatic innervation indeed has considerable significance under specific conditions ( Fig. 1.26).…”

Glucose and lipid metabolism after liver transplantation in inbred rats: consequences of hepatic denervation

“…Thus, by influencing circulating glucose, cholesterol, and insulin levels as well as peripheral insulin sensitivity, hepatic nerves constitute a powerful regulator of glucose and lipid metabolism. This gets lost after liver transplantation which results in persisting intrinsic hepatic denervation [8,9].…”