Focal liver necrosis appears early after partial hepatectomy and is dependent on T cells and antigen delivery from the gut

Noam Rudich, Gideon Zamir, Orit Pappo, Zipora Shlomai, Muhamad Faroja, Ido D. Weiss, Hanna Wald, Eithan Galun, Amnon Peled, Ori Wald*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Introduction: 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.

Original languageAmerican English
Pages (from-to)1273-1284
Number of pages12
JournalLiver International
Volume29
Issue number8
DOIs
StatePublished - 2009
Externally publishedYes

Keywords

  • Enterohepatic circulation
  • Liver regeneration
  • Necrosis

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