TY - JOUR
T1 - Xenogeneic Heterotopic Auxiliary Liver Transplantation (XHALT) promotes native liver regeneration in a Post-Hepatectomy Liver failure model
AU - Navarro-Alvarez, Nalu
AU - Machaidze, Zurab
AU - Schuetz, Christian
AU - Zhu, Alexander
AU - Liu, Weihui H.
AU - Shah, Jigesh A.
AU - Vagefi, Parsia A.
AU - Elias, Nahel
AU - Buhler, Leo
AU - Sachs, David H.
AU - Markmann, James F.
AU - Yeh, Heidi
N1 - Publisher Copyright:
© 2018 Navarro-Alvarez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2018/11
Y1 - 2018/11
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0207272
DO - 10.1371/journal.pone.0207272
M3 - Article
C2 - 30462716
AN - SCOPUS:85056964811
SN - 1932-6203
VL - 13
JO - PLoS One
JF - PLoS One
IS - 11
M1 - e0207272
ER -