PMID- 27913222
OWN - NLM
STAT- MEDLINE
DCOM- 20180306
LR  - 20181005
IS  - 1600-0641 (Electronic)
IS  - 0168-8278 (Linking)
VI  - 66
IP  - 4
DP  - 2017 Apr
TI  - Human liver regeneration in advanced cirrhosis is organized by the portal tree.
PG  - 778-786
LID - S0168-8278(16)30690-0 [pii]
LID - 10.1016/j.jhep.2016.11.014 [doi]
AB  - BACKGROUND & AIMS: In advanced cirrhosis new hepatocytic nodules are generated by
      budding of ductules in areas of parenchymal extinction. However, the vascular
      alterations in the areas of parenchymal extinction, the blood supply and the
      structure of the new hepatocytic nodules have not been analyzed in detail.
      METHODS: Explanted human cirrhotic livers of three different etiologies and two
      experimental rat models of cirrhosis were thoroughly examined. 3D reconstruction 
      of the immunohistochemically stained serial sections and casting of human and
      experimental cirrhotic livers have been used to reveal the structural
      organization of the regenerative buds. RESULTS: In areas of parenchymal
      extinction the skeleton of the liver, the portal tree is preserved. The
      developing regenerative nodules are positioned along the portal tree and are
      directly supplied by terminal portal venules. The expanding nodules grow along
      the trunks of the portal vein. Casting of human and experimental cirrhotic livers
      by colored resin confirms that nodules are supplied by portal blood. The two
      other members of the portal triads become separated from the portal veins.
      CONCLUSIONS: As the structure of the hepatocyte nodules (centrally located portal
      vein branches, bile ducts at the periphery, hepatic veins and arteries in the
      connective tissue) impedes the restoration of normal liver structure, the basic
      architecture of hepatic tissue suffers permanent damage. We suggest that
      "budding" may initiate the second, irreversible stage of cirrhosis. LAY SUMMARY: 
      Cirrhosis is the final common outcome of long lasting hepatic injury defined as
      the destruction of the normal liver architecture by scar tissue. In the late
      phase of cirrhosis stem cells-derived hepatocyte nodules appear along the
      branches of the portal vein suggesting an important role of this specially
      composed blood vessels (containing digestive end-products from the stomach and
      intestines) in liver regeneration. Our results contribute to a better
      understanding of this serious liver disease.
CI  - Copyright (c) 2016 European Association for the Study of the Liver. Published by 
      Elsevier B.V. All rights reserved.
FAU - Dezso, Katalin
AU  - Dezso K
AD  - Semmelweis University, First Department of Pathology and Experimental Cancer
      Research, Budapest, Hungary.
FAU - Rokusz, Andras
AU  - Rokusz A
AD  - Semmelweis University, First Department of Pathology and Experimental Cancer
      Research, Budapest, Hungary.
FAU - Bugyik, Edina
AU  - Bugyik E
AD  - Semmelweis University, First Department of Pathology and Experimental Cancer
      Research, Budapest, Hungary.
FAU - Szucs, Armanda
AU  - Szucs A
AD  - Semmelweis University, First Department of Pathology and Experimental Cancer
      Research, Budapest, Hungary.
FAU - Szuak, Andras
AU  - Szuak A
AD  - Semmelweis University, Department of Anatomy, Histology and Embryology, Budapest,
      Hungary.
FAU - Dorogi, Bence
AU  - Dorogi B
AD  - Department of Surgery, Budai Irgalmasrendi Hospital, Budapest, Hungary.
FAU - Kiss, Matyas
AU  - Kiss M
AD  - Semmelweis University, Department of Anatomy, Histology and Embryology, Budapest,
      Hungary.
FAU - Nemeskeri, Agnes
AU  - Nemeskeri A
AD  - Semmelweis University, Department of Anatomy, Histology and Embryology, Budapest,
      Hungary.
FAU - Nagy, Peter
AU  - Nagy P
AD  - Semmelweis University, First Department of Pathology and Experimental Cancer
      Research, Budapest, Hungary.
FAU - Paku, Sandor
AU  - Paku S
AD  - Semmelweis University, First Department of Pathology and Experimental Cancer
      Research, Budapest, Hungary; Tumor Progression Research Group, Joint Research
      Organization of the Hungarian Academy of Sciences and Semmelweis University,
      Budapest, Hungary. Electronic address: paku@korb1.sote.hu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161129
PL  - Netherlands
TA  - J Hepatol
JT  - Journal of hepatology
JID - 8503886
SB  - IM
MH  - Animals
MH  - Hepatocytes/pathology
MH  - Humans
MH  - Image Processing, Computer-Assisted
MH  - Imaging, Three-Dimensional
MH  - Liver Circulation
MH  - Liver Cirrhosis/*pathology/physiopathology
MH  - Liver Cirrhosis, Experimental/pathology/physiopathology
MH  - Liver Regeneration/*physiology
MH  - Male
MH  - Models, Anatomic
MH  - Neovascularization, Physiologic
MH  - Portal Vein/*pathology
MH  - Rats
MH  - Rats, Inbred F344
OTO - NOTNLM
OT  - *3D reconstruction
OT  - *Liver cirrhosis
OT  - *Regenerative nodules
OT  - *Vascular casting
EDAT- 2016/12/04 06:00
MHDA- 2018/03/07 06:00
CRDT- 2016/12/04 06:00
PHST- 2016/08/22 00:00 [received]
PHST- 2016/11/08 00:00 [revised]
PHST- 2016/11/13 00:00 [accepted]
PHST- 2016/12/04 06:00 [pubmed]
PHST- 2018/03/07 06:00 [medline]
PHST- 2016/12/04 06:00 [entrez]
AID - S0168-8278(16)30690-0 [pii]
AID - 10.1016/j.jhep.2016.11.014 [doi]
PST - ppublish
SO  - J Hepatol. 2017 Apr;66(4):778-786. doi: 10.1016/j.jhep.2016.11.014. Epub 2016 Nov
      29.