Focal liver necrosis appears early after partial hepatectomy and is dependent on T cells and antigen delivery from the gut.
BACKGROUND
Progressive liver failure may develop following removal of a large part of the liver or transplantation of a small for size liver graft. The pathophysiology of this clinical syndrome is only partially understood.


METHODS
We assessed liver damage and hepatocyte 5-bromo-2'-deoxyuridine (BrdU) incorporation following partial hepatectomy (PH) in C57BL/6, BALB/C and immune-deficient mice. Hepatic lymphocyte subpopulations were characterized. Lipopolysaccharide (LPS) treatment and bowel decontamination determined the role of gut antigens.


RESULTS
Discrete, round necrotic lesions were observed as early as 2 h following 70%, but not 30% PH. In immune competent mice the extent of hepatocyte necrosis inversely correlated with BrdU incorporation. T, natural killer and natural killer T cells were recruited to the liver early after PH; however, only T-cell depletion abrogated hepatic necrosis. Hepatic injury was significantly reduced in non-obese diabetic/severe combined immunodeficient mice undergoing PH, while BrdU incorporation was not affected. Liver injury was augmented by LPS injection and reduced by gut decontamination.


CONCLUSIONS
A distinct pattern of early focal hepatic necrosis is observed following extensive PH in mice. T cells infiltrating the liver immediately after PH and gut-derived antigens are indispensable for the observed liver necrosis and may thus provide therapeutic targets to ameliorate liver damage following PH.
Rudich
Noam
N
Laboratory for Surgical Research, Hadassah University Hospital, Jerusalem, Israel.
Zamir
Gideon
G
Pappo
Orit
O
Shlomai
Zipora
Z
Faroja
Muhamad
M
Weiss
Ido D
ID
Wald
Hanna
H
Galun
Eithan
E
Peled
Amnon
A
Wald
Ori
O
D019264:Adoptive Transfer; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D019138:Antibodies, Blocking / Q000494:pharmacology; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000276:immunology; D016026:Bone Marrow Transplantation; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000276:immunology*; D006498:Hepatectomy / Q000009:adverse effects*; D007422:Intestines / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008103:Liver Cirrhosis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D008115:Liver Regeneration / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D016513:Mice, SCID; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000276:immunology*
D000900:Anti-Bacterial Agents; D019138:Antibodies, Blocking; D000942:Antigens, Bacterial; D008070:Lipopolysaccharides; D001973:Bromodeoxyuridine