Hepatobiliary transporter expression and post-operative jaundice in patients undergoing partial hepatectomy

Liver Int. 2012 Jan;32(1):119-27. doi: 10.1111/j.1478-3231.2011.02625.x. Epub 2011 Aug 25.

Abstract

Background and aims: Post-operative hyperbilirubinaemia in patients undergoing liver resections is associated with high morbidity and mortality. Apart from different known factors responsible for the development of post-operative jaundice, little is known about the role of hepatobiliary transport systems in the pathogenesis of post-operative jaundice in humans after liver resection.

Methods: Two liver tissue samples were taken from 14 patients undergoing liver resection before and after Pringle manoeuvre. Patients were retrospectively divided into two groups according to post-operative bilirubin serum levels. The two groups were analysed comparing the results of hepatobiliary transporter [Na-taurocholate cotransporter (NTCP); multidrug resistance gene/phospholipid export pump(MDR3); bile salt export pump (BSEP); canalicular bile salt export pump (MRP2)], heat shock protein 70 (HSP70) expression as well as the results of routinely taken post-operative liver chemistry tests.

Results: Patients with low post-operative bilirubin had lower levels of NTCP, MDR3 and BSEP mRNA compared to those with high bilirubin after Pringle manoeuvre. HSP70 levels were significantly higher after ischaemia-reperfusion (IR) injury in both groups resulting in 4.5-fold median increase. Baseline median mRNA expression of all four transporters prior to Pringle manoeuvre tended to be lower in the low bilirubin group whereas expression of HSP70 was higher in the low bilirubin group compared to the high bilirubin group.

Discussion: Higher mRNA levels of HSP70 in the low bilirubin group could indicate a possible protective effect of high HSP70 levels against IR injury. Although the exact role of hepatobiliary transport systems in the development of post-operative hyper bilirubinemia is not yet completely understood, this study provides new insights into the molecular aspects of post-operative jaundice after liver surgery.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • ATP Binding Cassette Transporter, Subfamily B, Member 11
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Aged
  • Bilirubin / blood
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Female
  • Gene Expression
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism
  • Hepatectomy*
  • Humans
  • Jaundice / genetics
  • Jaundice / metabolism*
  • Jaundice / pathology
  • Liver Function Tests
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / secondary
  • Male
  • Middle Aged
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins / genetics
  • Multidrug Resistance-Associated Proteins / metabolism
  • Organic Anion Transporters, Sodium-Dependent / genetics
  • Organic Anion Transporters, Sodium-Dependent / metabolism
  • Postoperative Complications
  • Retrospective Studies
  • Symporters / genetics
  • Symporters / metabolism

Substances

  • ABCB11 protein, human
  • ABCC2 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 11
  • ATP-Binding Cassette Transporters
  • Carrier Proteins
  • HSP70 Heat-Shock Proteins
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins
  • Organic Anion Transporters, Sodium-Dependent
  • Symporters
  • sodium-bile acid cotransporter
  • multidrug resistance protein 3
  • Bilirubin