Postoperative bile leakage inhibits liver regeneration after 70% hepatectomy in rats

J Invest Surg. 2013 Feb;26(1):36-45. doi: 10.3109/08941939.2012.691603.


Background: Postoperative bile leakage is a typical complication in liver surgery. The influence of small bile leakage and concomitant bile peritonitis on the regenerative capacity of the liver remnant has not yet been investigated thoroughly.

Material and methods: Fifty-four rats were randomized in the following groups: Sham operation (Sh), 70% liver resection (LR), and 70% LR with simultaneous induction of a small bile leakage. Animals were euthanized 6, 24, 48, and 96 hr after surgery. Liver regeneration was measured by relative liver weight, mitotic index, Ki-67 immunohistochemistry, and BrdU labeling index. Liver function was evaluated by thromboplastin time, serum bilirubin, and albumin levels as well as indocyanine green plasma disappearance rate (ICG-PDR). The inflammatory response was characterized by assessment of the hepatic transcription of TNF-α, IL-6, and TGF-β and the serum concentration of IL-1β. In addition, myeloperoxidase (MPO) activity in liver tissue was measured. Transaminases and histological sections of the liver were used as markers for hepatocellular damage, and the bacterial concentration in different organs was quantified.

Results: With a small bile leakage, mitotic index was reduced by 89% ( p < .05) and the number of Ki-67 positive hepatocytes was reduced by 92% ( p < .05) 24 hr after LR. Likewise, the ICG-PDR dropped by 57% ( p < .05). No differences in liver histology were observed between the groups. With bile leakage, the postoperative transcription of cytokines was markedly higher. A bacterial superinfection could be excluded.

Conclusion: Small intraabdominal bile leakage can suppress liver function and impair the regenerative capacity of the liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteria / isolation & purification
  • Bile*
  • Biomarkers
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Fluorescent Dyes / pharmacokinetics
  • Gene Expression Regulation
  • Hepatectomy / adverse effects*
  • Indocyanine Green / pharmacokinetics
  • Liver / metabolism
  • Liver / microbiology
  • Liver / pathology
  • Liver Function Tests
  • Liver Regeneration / physiology*
  • Lymph Nodes / microbiology
  • Male
  • Mitotic Index
  • Neutrophil Activation
  • Organ Size
  • Peritonitis / etiology
  • Peritonitis / genetics
  • Peritonitis / physiopathology*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Viscera / microbiology


  • Biomarkers
  • Cytokines
  • Fluorescent Dyes
  • Indocyanine Green