Prospective Non-randomized Trial to Study Expression of Mediators of Post Hepatectomy Liver Regeneration(PHLR) and Compare With a Non-hepatectomy Group: a Pilot Study

Prospective non-randomized trial to study expression of mediators of post hepatectomy liver regeneration(PHLR) and compare with a non-hepatectomy group: a pilot study

Background : Experimental studies using post hepatectomy animal models have been used to study the mechanism of liver regeneration. Hepatectomy for various diseases and living donor liver transplant provide a good human model to study in vivo mechanism of liver regeneration. These studies are necessary for the clinical application of the knowledge obtained by animal experiments and will guide further research to develop new modalities for the management of hepatic failure, cirrhosis and cancer.

Introduction :

Liver is a vital organ which serve various metabolic and protective functions necessary for the maintenance of life and it has got inherent potential to regenerate and restore volume after its partial resection. Liver regeneration after hepatectomy occurs mainly by proliferation of mature hepatocytes (Fausto N 2003 & 2004); changes in portal haemodyanmics and cytokines (IL-6, TNF- α ) considered as most important trigger factors for this process. (Abhshagen K et al 2012, Scotte M et al 1997) It is proposed that increased delivery of portal blood to remnant liver produces shear stress injury leading to release of factors like NO and VEGF which activate the regeneration cascade (Marabushi et al 2004). Cytokines (IL-6 and TNF-α), NO and VEGF act on pro HGF (inactive hepatocyte growth factor) to convert it into active HGF which act through Met receptors to further activate STAT-3 which is a key mediator of early phase of PHLR. (Abhshgen K et al 2008,Cresman DE et al 1996, Cressman DE1997, Sudo K et al 2008, Borowicak M et al 2004, Paranjpe S et al 2007) Increased delivery of portal blood to remnant liver also increases per unit availability of amino acids, pancreatic hormones, gut derived endotoxins and other hepatotrophic factors, all these may act directly to activate DNA replication. ( Bucher NL et al 1977, Riehle KJ et al 2011) Administration of amino acid mixture to intact rats induces a wave of hepatocyte replication, and its deprivation blocks PHLR. (Mead JE et al 1990) Insulin, Glucagon and Growth hormone also have a significant impact on liver regeneration. (Bucher NLR 1976, Shi min luo et al 2004, Amal ZS et al 2011 ) The capability of liver to regenerate after its partial resection permits us to perform hepatectomy for living donor liver transplantation, hepatic neoplasms and biliary cancers. Hepatectomy for these conditions also provides us a good model to study the in vivo mechanism of liver regeneration in human beings. These studies are important for the clinical application of the knowledge obtained by experimental studies on post hepatectomy animals. These studies will help us to know the mediators of various phases of post hepatectomy liver regeneration (PHLR) and will guide future research to develop new approaches for the prevention and management of life threatening post hepatectomy complications like "Small for size syndrome", hepatic failure. These trails will help to understand in vivo control of cellular proliferation and may prove vital to develop new therapeutic approaches to treat cirrhosis and cancer.

Null hypothesis: Expression of mediators of post hepatectomy liver regeneration (PHLR) is not different between hepatectomy (study group) and non hepatectomy group (control group).