Liver atrophy after percutaneous transhepatic portal embolization occurs in two histological phases: Hepatocellular atrophy followed by apoptosis

Yasuhito Iwao, Hidenori Ojima, Tatsushi Kobayashi, Yoji Kishi, Satoshi Nara, Minoru Esaki, Kazuaki Shimada, Nobuyoshi Hiraoka, Minoru Tanabe, Yae Kanai

Research output: Contribution to journalArticle

Abstract

AIM To clarify the histological changes associated with liver atrophy after percutaneous transhepatic portal embolization (PTPE) in pigs and humans. METHODS As a preliminary study, we performed pathological examinations of liver specimens from five pigs that had undergone PTPE in a time-dependent model of liver atrophy. In specimens from embolized lobes (EMB) and nonembolized lobes (controls), we measured the portal vein to central vein distance (PV-CV), the area and number of hepatocytes per lobule, and apoptotic activity using the terminal deoxynucleotidyl transferase dUTP nickend labeling assay. Immunohistochemical reactivities were evaluated for light chain 3 (LC3) and lysosomal-associated membrane protein 2 (LAMP2) as autophagy markers and for glutamine synthetase and cytochrome P450 2E1 (CYP2E1) as metabolic zonation markers. Samples from ten human livers taken 20-36 d after PTPE were similarly examined. RESULTS PV-CVs and lobule areas did not differ between EMB and controls at day 0, but were lower in EMB than in controls at weeks 2, 4, and 6 (P ≤ 0.001). Hepatocyte numbers were not significantly reduced in EMB at day 0 and week 2 but were reduced at weeks 4 and 6 (P ≤ 0.05). Apoptotic activity was higher in EMB than in controls at day 0 and week 4. LC3 and LAMP2 staining peaked in EMB at week 2, with no significant difference between EMB and controls at weeks 4 and 6. Glutamine synthetase and CYP2E1 zonation in EMB at weeks 2, 4, and 6 were narrower than those in controls. Human results were consistent with those of porcine specimens. CONCLUSION The mechanism of liver atrophy after PTPE has two histological phases: Hepatocellular atrophy is likely caused by autophagy in the first 2 wk and apoptosis thereafter.

Original languageEnglish
Pages (from-to)1227-1238
Number of pages12
JournalWorld Journal of Hepatology
Volume9
Issue number32
DOIs
Publication statusPublished - 2017 Nov 18

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Atrophy
Lysosomal-Associated Membrane Protein 2
Apoptosis
Liver
Cytochrome P-450 CYP2E1
Glutamate-Ammonia Ligase
Swine
Autophagy
Hepatocytes
Light
DNA Nucleotidylexotransferase
Portal Vein
Veins
Staining and Labeling

Keywords

  • Apoptosis
  • Autophagy
  • Liver atrophy
  • Lobule
  • Portal vein embolization
  • Zonation

ASJC Scopus subject areas

  • Hepatology

Cite this

Liver atrophy after percutaneous transhepatic portal embolization occurs in two histological phases : Hepatocellular atrophy followed by apoptosis. / Iwao, Yasuhito; Ojima, Hidenori; Kobayashi, Tatsushi; Kishi, Yoji; Nara, Satoshi; Esaki, Minoru; Shimada, Kazuaki; Hiraoka, Nobuyoshi; Tanabe, Minoru; Kanai, Yae.

In: World Journal of Hepatology, Vol. 9, No. 32, 18.11.2017, p. 1227-1238.

Research output: Contribution to journalArticle

Iwao, Yasuhito ; Ojima, Hidenori ; Kobayashi, Tatsushi ; Kishi, Yoji ; Nara, Satoshi ; Esaki, Minoru ; Shimada, Kazuaki ; Hiraoka, Nobuyoshi ; Tanabe, Minoru ; Kanai, Yae. / Liver atrophy after percutaneous transhepatic portal embolization occurs in two histological phases : Hepatocellular atrophy followed by apoptosis. In: World Journal of Hepatology. 2017 ; Vol. 9, No. 32. pp. 1227-1238.
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abstract = "AIM To clarify the histological changes associated with liver atrophy after percutaneous transhepatic portal embolization (PTPE) in pigs and humans. METHODS As a preliminary study, we performed pathological examinations of liver specimens from five pigs that had undergone PTPE in a time-dependent model of liver atrophy. In specimens from embolized lobes (EMB) and nonembolized lobes (controls), we measured the portal vein to central vein distance (PV-CV), the area and number of hepatocytes per lobule, and apoptotic activity using the terminal deoxynucleotidyl transferase dUTP nickend labeling assay. Immunohistochemical reactivities were evaluated for light chain 3 (LC3) and lysosomal-associated membrane protein 2 (LAMP2) as autophagy markers and for glutamine synthetase and cytochrome P450 2E1 (CYP2E1) as metabolic zonation markers. Samples from ten human livers taken 20-36 d after PTPE were similarly examined. RESULTS PV-CVs and lobule areas did not differ between EMB and controls at day 0, but were lower in EMB than in controls at weeks 2, 4, and 6 (P ≤ 0.001). Hepatocyte numbers were not significantly reduced in EMB at day 0 and week 2 but were reduced at weeks 4 and 6 (P ≤ 0.05). Apoptotic activity was higher in EMB than in controls at day 0 and week 4. LC3 and LAMP2 staining peaked in EMB at week 2, with no significant difference between EMB and controls at weeks 4 and 6. Glutamine synthetase and CYP2E1 zonation in EMB at weeks 2, 4, and 6 were narrower than those in controls. Human results were consistent with those of porcine specimens. CONCLUSION The mechanism of liver atrophy after PTPE has two histological phases: Hepatocellular atrophy is likely caused by autophagy in the first 2 wk and apoptosis thereafter.",
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T2 - Hepatocellular atrophy followed by apoptosis

AU - Iwao, Yasuhito

AU - Ojima, Hidenori

AU - Kobayashi, Tatsushi

AU - Kishi, Yoji

AU - Nara, Satoshi

AU - Esaki, Minoru

AU - Shimada, Kazuaki

AU - Hiraoka, Nobuyoshi

AU - Tanabe, Minoru

AU - Kanai, Yae

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N2 - AIM To clarify the histological changes associated with liver atrophy after percutaneous transhepatic portal embolization (PTPE) in pigs and humans. METHODS As a preliminary study, we performed pathological examinations of liver specimens from five pigs that had undergone PTPE in a time-dependent model of liver atrophy. In specimens from embolized lobes (EMB) and nonembolized lobes (controls), we measured the portal vein to central vein distance (PV-CV), the area and number of hepatocytes per lobule, and apoptotic activity using the terminal deoxynucleotidyl transferase dUTP nickend labeling assay. Immunohistochemical reactivities were evaluated for light chain 3 (LC3) and lysosomal-associated membrane protein 2 (LAMP2) as autophagy markers and for glutamine synthetase and cytochrome P450 2E1 (CYP2E1) as metabolic zonation markers. Samples from ten human livers taken 20-36 d after PTPE were similarly examined. RESULTS PV-CVs and lobule areas did not differ between EMB and controls at day 0, but were lower in EMB than in controls at weeks 2, 4, and 6 (P ≤ 0.001). Hepatocyte numbers were not significantly reduced in EMB at day 0 and week 2 but were reduced at weeks 4 and 6 (P ≤ 0.05). Apoptotic activity was higher in EMB than in controls at day 0 and week 4. LC3 and LAMP2 staining peaked in EMB at week 2, with no significant difference between EMB and controls at weeks 4 and 6. Glutamine synthetase and CYP2E1 zonation in EMB at weeks 2, 4, and 6 were narrower than those in controls. Human results were consistent with those of porcine specimens. CONCLUSION The mechanism of liver atrophy after PTPE has two histological phases: Hepatocellular atrophy is likely caused by autophagy in the first 2 wk and apoptosis thereafter.

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KW - Autophagy

KW - Liver atrophy

KW - Lobule

KW - Portal vein embolization

KW - Zonation

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