Human liver regeneration following massive hepatic necrosis: Two distinct patterns

Katalin Dezső, P. Nagy, S. Paku

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background and Aim: Massive hepatic necrosis is a rare but often fatal complication of various liver injuries. Nevertheless, some patients can survive by spontaneous hepatic regeneration. It is known that surviving hepatocytes and/or progenitor cells can participate in this process but the mechanism of hepatic recovery is vague. Methods: We examined 13 explanted human livers removed for acute liver failure. Combined immunohistochemistry, digital image analysis, and three-dimensional reconstruction of serial sections were applied. Results: Two patterns of regeneration could be distinguished. In livers with centrilobular necrosis, the surviving injured periportal hepatocytes started to proliferate and arrange into acinar structures and expressed α-fetoprotein. If the injury wiped out almost all hepatocytes, large areas of parenchymal loss were invaded by an intense ductular reaction. The cells at the distal pole of the ductules differentiated into hepatocytes and formed foci organized by the branches of the portal vein. The expanding foci often containing complete portal triads were arranged around surviving central veins. Their fusion eventually could be an attempt to re-establish the hepatic lobules. Conclusions: Regeneration of human livers following massive hepatic necrosis can occur in two ways—either through proliferation of α-fetoprotein-positive acinary-arranged hepatocytes or through ductular progenitor cells, with the latter being less efficient. Further investigation of these regenerative pathways may help identify biomarkers for likelihood of complete regeneration and hence have therapeutic implications.

Original languageEnglish
JournalJournal of Gastroenterology and Hepatology (Australia)
DOIs
Publication statusPublished - Jan 1 2019

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Massive Hepatic Necrosis
Liver Regeneration
Hepatocytes
Liver
Fetal Proteins
Regeneration
Stem Cells
Three-Dimensional Imaging
Acute Liver Failure
Wounds and Injuries
Portal Vein
Veins
Necrosis
Biomarkers
Immunohistochemistry

Keywords

  • 3D reconstruction
  • foci
  • fulminant liver failure
  • portal vein
  • α-fetoprotein

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

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title = "Human liver regeneration following massive hepatic necrosis: Two distinct patterns",
abstract = "Background and Aim: Massive hepatic necrosis is a rare but often fatal complication of various liver injuries. Nevertheless, some patients can survive by spontaneous hepatic regeneration. It is known that surviving hepatocytes and/or progenitor cells can participate in this process but the mechanism of hepatic recovery is vague. Methods: We examined 13 explanted human livers removed for acute liver failure. Combined immunohistochemistry, digital image analysis, and three-dimensional reconstruction of serial sections were applied. Results: Two patterns of regeneration could be distinguished. In livers with centrilobular necrosis, the surviving injured periportal hepatocytes started to proliferate and arrange into acinar structures and expressed α-fetoprotein. If the injury wiped out almost all hepatocytes, large areas of parenchymal loss were invaded by an intense ductular reaction. The cells at the distal pole of the ductules differentiated into hepatocytes and formed foci organized by the branches of the portal vein. The expanding foci often containing complete portal triads were arranged around surviving central veins. Their fusion eventually could be an attempt to re-establish the hepatic lobules. Conclusions: Regeneration of human livers following massive hepatic necrosis can occur in two ways—either through proliferation of α-fetoprotein-positive acinary-arranged hepatocytes or through ductular progenitor cells, with the latter being less efficient. Further investigation of these regenerative pathways may help identify biomarkers for likelihood of complete regeneration and hence have therapeutic implications.",
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AU - Dezső, Katalin

AU - Nagy, P.

AU - Paku, S.

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N2 - Background and Aim: Massive hepatic necrosis is a rare but often fatal complication of various liver injuries. Nevertheless, some patients can survive by spontaneous hepatic regeneration. It is known that surviving hepatocytes and/or progenitor cells can participate in this process but the mechanism of hepatic recovery is vague. Methods: We examined 13 explanted human livers removed for acute liver failure. Combined immunohistochemistry, digital image analysis, and three-dimensional reconstruction of serial sections were applied. Results: Two patterns of regeneration could be distinguished. In livers with centrilobular necrosis, the surviving injured periportal hepatocytes started to proliferate and arrange into acinar structures and expressed α-fetoprotein. If the injury wiped out almost all hepatocytes, large areas of parenchymal loss were invaded by an intense ductular reaction. The cells at the distal pole of the ductules differentiated into hepatocytes and formed foci organized by the branches of the portal vein. The expanding foci often containing complete portal triads were arranged around surviving central veins. Their fusion eventually could be an attempt to re-establish the hepatic lobules. Conclusions: Regeneration of human livers following massive hepatic necrosis can occur in two ways—either through proliferation of α-fetoprotein-positive acinary-arranged hepatocytes or through ductular progenitor cells, with the latter being less efficient. Further investigation of these regenerative pathways may help identify biomarkers for likelihood of complete regeneration and hence have therapeutic implications.

AB - Background and Aim: Massive hepatic necrosis is a rare but often fatal complication of various liver injuries. Nevertheless, some patients can survive by spontaneous hepatic regeneration. It is known that surviving hepatocytes and/or progenitor cells can participate in this process but the mechanism of hepatic recovery is vague. Methods: We examined 13 explanted human livers removed for acute liver failure. Combined immunohistochemistry, digital image analysis, and three-dimensional reconstruction of serial sections were applied. Results: Two patterns of regeneration could be distinguished. In livers with centrilobular necrosis, the surviving injured periportal hepatocytes started to proliferate and arrange into acinar structures and expressed α-fetoprotein. If the injury wiped out almost all hepatocytes, large areas of parenchymal loss were invaded by an intense ductular reaction. The cells at the distal pole of the ductules differentiated into hepatocytes and formed foci organized by the branches of the portal vein. The expanding foci often containing complete portal triads were arranged around surviving central veins. Their fusion eventually could be an attempt to re-establish the hepatic lobules. Conclusions: Regeneration of human livers following massive hepatic necrosis can occur in two ways—either through proliferation of α-fetoprotein-positive acinary-arranged hepatocytes or through ductular progenitor cells, with the latter being less efficient. Further investigation of these regenerative pathways may help identify biomarkers for likelihood of complete regeneration and hence have therapeutic implications.

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