Transplanted liver: Consequences of denervation for liver functions

Abstract

Following liver transplantation, all hepatic nerves are transected; thus, liver allografts are completely isolated from neural control of their hosts. Despite this absolute denervation, liver allograft function does not appear to be significantly impaired after successful transplantation. In experimental animal models, hepatic denervation has no major effects on bile acid production and biotransformation, while it increases blood pressure and salt retention; decreases the number of hepatic progenitor cells, cholangiocyte proliferation, and liver regeneration; and influences the hepatic microcirculation, diet behavior, and glycemic control. In humans, hepatic denervation after liver transplantation has no major deleterious effects on bile secretion, liver regeneration, and hepatic blood flow. Insulin resistance and postprandial hyperglycemia, changes in ingestion behavior, and reduced stimulation of hepatic progenitor cells in the canals of Hering are the major side effects of absent liver innervation. Despite these abnormalities, patients can lead a new life with improved quality of life. © 2004 Wiley-Liss, Inc. Key words: liver transplantation; denervation; function; hepaticLiver transplantation is the ultimate treatment for patients with acute fulminant and chronic liver failure. The results of liver transplantation are good, with a 1-year survival of 90 -95% and a 10-year survival of 50 -60%. Because of a shortage in cadaveric donors, living-related liver transplantation is a good option to overcome this problem.The autonomic nerves of the liver are formed by an anterior plexus (around the hepatic artery) and a posterior plexus (surrounds portal vein and bile duct). Parasympathetic nerves are derived from the vagus nerve and the sympathetic fibers from the celiac ganglion. Sensory nerve endings are present in the liver capsule, central veins, and bile ducts. Most of the afferent nerves from the liver run via the vagus and splanchnic nerves, but some also to the right phrenic nerve. The afferent nerves register information from nocireceptors, osmo-and baroreceptors, as well as ionic and metabolic receptors (Bathal and Grossman, 1999).Following liver transplantation, the hepatic nerves are inevitably transected below the porta hepatis or at the hepatoduodenal ligament; thus, liver allografts are completely isolated from the neural control of their hosts. Despite this absolute denervation, the liver allograft does not appear to be significantly compromised after successful transplantation. There is no obvious deficiency in the regulation of liver metabolism (production of proteins such as albumin and coagulation factors, metabolization) and bile production. At first blush, it seems that under normal circumstances, hormones and substrates reaching the liver by circulation are responsible for control of the organ function, and that the role of hepatic nerves is mainly restricted to situations of physiological stress.However, a more profound search revealed that hepatic denervation has a lot of consequences...

The Effect of Denervation on Liver Regeneration in Partially Hepatectomized Rats

“…In our experiment, general liver function tests (liver enzymes, bilirubin) were not altered after denervation at 24 h (data not shown), although there have been several reports that showed effects on bile acid synthesis, drug metabolism, glycemia, and bile secretion [26]. Detailed data regarding changes in liver metabolism after denervation needs further investigation.…”

Metabolic syndrome and liver transplantation: A review and guide to management

“…The transplanted liver itself may contribute to the increase in insulin resistance as denervation/vagotomy of the liver during liver transplantation has been associated with increased insulin resistance [53]. After a liver transplant, patients are on medications that may impact and complicate insulin sensitivity.…”

Flow Competition between Hepatic Arterial and Portal Venous flow during Hypothermic Machine Perfusion Preservation of Porcine Livers

“…NO, CO), and the effects of some drugs such as volatile anaesthetics, β-adrenergic stimulants, calcium antagonists (20).…”

“…Such an alteration could be multifactorial and induced by the denervation, the use of an a-cellular perfusion solution (essentially different from plasma, absence of humoral factors), the hypothermic conditions leading to a decreased metabolism and enzymatic activity, the lack of oxygen and essential nutrients. Denervation can probably be neglected as a possible cause, since hepatic denervation has been shown to have no major deleterious effects on hepatic blood flow after liver transplantation (20). A factor which is more likely to contribute is the negative influence of the cold temperature (and concomitant intracellular energy depletion) on the pre-sinusoidal sphincters.…”