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

Nalu Navarro-Alvarez, Zurab Machaidze, Christian Schuetz, Alexander Zhu, Weihui H. Liu, Jigesh A. Shah, Parsia A. Vagefi, Nahel Elias, Leo Buhler, David H. Sachs, James F. Markmann, Heidi Yeh

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere0207272
JournalPloS one
Volume13
Issue number11
DOIs
StatePublished - Nov 2018
Externally publishedYes

Fingerprint

liver regeneration
liver transplant
liver failure
Liver Regeneration
Liver Failure
Hepatectomy
Liver
Liver Transplantation
liver
Kernicterus
death
Transplants
Miniature Swine
miniature swine
encephalopathy
Acute Liver Failure
Papio
immunosuppression
ascites
bilirubin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Xenogeneic Heterotopic Auxiliary Liver Transplantation (XHALT) promotes native liver regeneration in a Post-Hepatectomy Liver failure model. / Navarro-Alvarez, Nalu; Machaidze, Zurab; Schuetz, Christian; Zhu, Alexander; Liu, Weihui H.; Shah, Jigesh A.; Vagefi, Parsia A.; Elias, Nahel; Buhler, Leo; Sachs, David H.; Markmann, James F.; Yeh, Heidi.

In: PloS one, Vol. 13, No. 11, e0207272, 11.2018.

Research output: Contribution to journalArticle

Navarro-Alvarez, N, Machaidze, Z, Schuetz, C, Zhu, A, Liu, WH, Shah, JA, Vagefi, PA, Elias, N, Buhler, L, Sachs, DH, Markmann, JF & Yeh, H 2018, 'Xenogeneic Heterotopic Auxiliary Liver Transplantation (XHALT) promotes native liver regeneration in a Post-Hepatectomy Liver failure model', PloS one, vol. 13, no. 11, e0207272. https://doi.org/10.1371/journal.pone.0207272
Navarro-Alvarez, Nalu ; Machaidze, Zurab ; Schuetz, Christian ; Zhu, Alexander ; Liu, Weihui H. ; Shah, Jigesh A. ; Vagefi, Parsia A. ; Elias, Nahel ; Buhler, Leo ; Sachs, David H. ; Markmann, James F. ; Yeh, Heidi. / Xenogeneic Heterotopic Auxiliary Liver Transplantation (XHALT) promotes native liver regeneration in a Post-Hepatectomy Liver failure model. In: PloS one. 2018 ; Vol. 13, No. 11.
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