NAFLD Induction Delays Postoperative Liver Regeneration of ALPPS in Rats

Dig Dis Sci. 2019 Feb;64(2):456-468. doi: 10.1007/s10620-018-5346-3. Epub 2018 Nov 23.

Abstract

Background: Associating liver partition and portal vein ligation (ALPPS) is a promising two-step hepatectomy that is beneficial for accumulative regeneration of the future liver remnant (FLR) and avoids postoperative liver failure.

Aims: Our study aimed to evaluate whether nonalcoholic fatty liver disease affected the liver regeneration induced by ALPPS.

Methods: Sprague-Dawley rats fed a high-fat diet were used to construct the NAFLD model. ALPPS were performed, and blood and future liver remnant samples were collected at postoperative days 1 (POD1), POD3, and POD7.

Results: The hepatic regeneration rate (HRR) of ALPPS was higher than that of portal vein ligation (PVL) at POD3 and POD7 (p < 0.05), and the number of Ki-67-positive hepatocytes (POD3) and CD68-positive Kupffer cells (POD7) per visual field was higher in the ALPPS group than in the PVL group (p < 0.05). The serum TNF-α, hepatocyte growth factor protein, and the serum IL-6 level were higher in the ALPPS group than in the PVL group at POD3 and POD7. Compared with those of the standard laboratory diet (SLD)-fed rats, the rats with NAFLD exhibited a decrease in the HRR, Ki-67-positive hepatocytes, and CD68-positive Kupffer cells in the FLR. The number of CD68-positive Kupffer cells was lower in rats with NAFLD than that in SLD-fed rats; noteworthily, the serum level of IL-6 and TNF-α changed dramatically after surgeries.

Conclusions: NAFLD induction delayed liver regeneration induced by the ALPPS procedure, which might be associated with hepatocyte proliferation and the number of Kupffer cells.

Keywords: ALPPS; Hepatocyte proliferation; Kupffer cells; Liver regeneration; NAFLD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Cholesterol / blood
  • Diet, High-Fat
  • Hepatectomy / methods*
  • Hepatocyte Growth Factor / blood
  • Interleukin-6 / blood
  • Ligation
  • Liver / pathology*
  • Liver Neoplasms / surgery
  • Liver Regeneration*
  • Male
  • Non-alcoholic Fatty Liver Disease / pathology*
  • Organ Size
  • Portal Vein / surgery*
  • Postoperative Period
  • Rats
  • Rats, Sprague-Dawley
  • Triglycerides / blood
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Il6 protein, rat
  • Interleukin-6
  • Triglycerides
  • Tumor Necrosis Factor-alpha
  • Hepatocyte Growth Factor
  • Cholesterol
  • Aspartate Aminotransferases
  • Alanine Transaminase