Massive hepatic necrosis with large regenerative nodules

Kim, Haeryoung; Park, Young Nyun

doi:10.3350/kjhep.2010.16.3.334

Cited by 3 publications

(1 citation statement)

References 5 publications

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“…In this study we investigated consequences of constitutive expression of vFLIP, a Caspase-8 inhibitor 20,23,33,34 , in hepatic epithelial cells. Expression of this viral protein was sufficient to induce histopathological features of acute viral hepatitis (AVH) and acute-on-chronic liver failure (ACLF) with extended areas of hepatocellular necrosis associated with severe loss of hepatocytes 35,36 . At a molecular level, we uncovered that hepatocellular death in vFlip AlbCre+ mice was mediated by regulated necrosis, leading to impaired liver homeostasis including compromised bile acid biosynthesis and transport.…”

Section: Discussionmentioning

confidence: 99%

Modulation of the extrinsic cell death signaling pathway by viral Flip induces acute-death mediated liver failure

et al. 2019

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During viral infections viruses express molecules that interfere with the host-cell death machinery and thus inhibit cell death responses. For example the viral FLIP (vFLIP) encoded by Kaposi’s sarcoma-associated herpesvirus interacts and inhibits the central cell death effector, Caspase-8. In order to analyze the impact of anti-apoptotic viral proteins, like vFlip, on liver physiology in vivo, mice expressing vFlip constitutively in hepatocytes (vFlipAlbCre+) were generated. Transgenic expression of vFlip caused severe liver tissue injury accompanied by massive hepatocellular necrosis and inflammation that finally culminated in early postnatal death of mice. On a molecular level, hepatocellular death was mediated by RIPK1-MLKL necroptosis driven by an autocrine TNF production. The loss of hepatocytes was accompanied by impaired bile acid production and disruption of the bile duct structure with impact on the liver-gut axis. Notably, embryonic development and tissue homeostasis were unaffected by vFlip expression. In summary our data uncovered that transgenic expression of vFlip can cause severe liver injury in mice, culminating in multiple organ insufficiency and death. These results demonstrate that viral cell death regulatory molecules exhibit different facets of activities beyond the inhibition of cell death that may merit more sophisticated in vitro and in vivo analysis.

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Section: Discussionmentioning

confidence: 99%

Modulation of the extrinsic cell death signaling pathway by viral Flip induces acute-death mediated liver failure

et al. 2019

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Interpretation of core biopsy of liver mass lesions: A comparison study between cytopathologist and gastrointestinal pathologist

Washburn

Yang

2019

Annals of Diagnostic Pathology

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Human liver regeneration following massive hepatic necrosis: Two distinct patterns

Dezső

Nagy

Paku

2019

J of Gastro and Hepatol

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Background and AimMassive 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.MethodsWe examined 13 explanted human livers removed for acute liver failure. Combined immunohistochemistry, digital image analysis, and three‐dimensional reconstruction of serial sections were applied.ResultsTwo 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.ConclusionsRegeneration 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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Massive hepatic necrosis with large regenerative nodules

Cited by 3 publications

References 5 publications

Modulation of the extrinsic cell death signaling pathway by viral Flip induces acute-death mediated liver failure

Modulation of the extrinsic cell death signaling pathway by viral Flip induces acute-death mediated liver failure

Interpretation of core biopsy of liver mass lesions: A comparison study between cytopathologist and gastrointestinal pathologist

Human liver regeneration following massive hepatic necrosis: Two distinct patterns

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