Xenogeneic Heterotopic Auxiliary Liver transplantation (XHALT) promotes native liver regeneration in a Post-Hepatectomy Liver failure model

PLoS One. 2018 Nov 21;13(11):e0207272. doi: 10.1371/journal.pone.0207272. eCollection 2018.

Abstract

The liver's regenerative capacity is unique, but too small a segment can overwhelm its ability to simultaneously regenerate and support the host, resulting in liver dysfunction and death. Here we tested a temporary Xenogeneic Heterotopic Auxiliary Liver Transplant (XHALT) from Gal-KO miniature swine in a baboon model of Post-Hepatectomy Liver Failure (PHLF) by 90%- hepatectomy. Immunosuppression consisted of CVF, ATG, FK 506 and steroids. 90%-hepatectomized animals died within 4-5 days with the clinical picture of PHLF, (high LFTs and bilirubin, ascites, encephalopathy and coagulopathy). The 10% remnants had macroscopic and histological evidence of severe steatosis and absence of hepatocyte replication. In contrast, the addition of XHALT prolonged survival up to 11 days, with the cause of death being sepsis, rather than liver failure. The remnant liver appeared grossly normal, and on histology, there was no evidence of fatty infiltration, but there was pronounced Ki-67 staining. In conclusion, temporary auxiliary xenografts have the potential to support a small for size liver graft while it grows to adequate size or provide an opportunity for organ recovery in acute liver failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Disease Models, Animal
  • Galactosyltransferases / deficiency
  • Galactosyltransferases / genetics
  • Gene Knockout Techniques
  • Graft Survival
  • Hepatectomy
  • Heterografts
  • Liver Failure / pathology
  • Liver Failure / physiopathology
  • Liver Failure / surgery*
  • Liver Regeneration / physiology*
  • Liver Transplantation / methods*
  • Papio
  • Swine
  • Swine, Miniature
  • Transplantation, Heterotopic

Substances

  • Galactosyltransferases
  • alpha-1,3-galactosyltransferase 1, porcine

Grants and funding

This study was supported by The Charles A. King Trust Postdoctoral Research Fellowship (https://hria.org/tmf/king/) (NNA) and the Polsky Clinician-Scientist Award, fund #222943. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.