CLINICAL STUDIES Hepatobiliary transporter expression and post-operative jaundice in patients undergoing partial hepatectomy Gerwin A. Bernhardt 1,2 , Gernot Zollner 3 , Herwig Cerwenka 1 , Peter Kornprat 1 , Peter Fickert 3 , Heinz Bacher 1 , Georg Werkgartner 1 , Gabriele Mu ¨ ller 4 , Kurt Zatloukal 5 , Hans-Jörg Mischinger 1,2 and Michael Trauner 3,6 1 Division of General Surgery, Department of Surgery, Medical University of Graz, Graz, Austria 2 Department of Surgery, District Hospital of Voitsberg Voitsberg, Austria 3 Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria 4 Division of General Anaesthesiology, Department of Anaesthesiology and Intensive Care Medicine, Medical University of Graz Graz, Austria 5 Institute of Pathology Medical University of Graz, Graz, Austria 6 Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria Keywords cholestasis – hepatectomy – hepatobiliary transporter system – ischaemia–reperfusion injury – liver proteins – liver surgery – post- operative jaundice – Pringle manoeuvre Correspondence Dr Gerwin Alexander Bernhardt Division of General Surgery, Department of Surgery, Medical University Graz Auenbruggerplatz 29, 8036 Graz, Austria Tel: +43 3142 201 2916 Fax: +43 316 385 14666 e-mail: gerwin.bernhardt@lkh-voitsberg.at Received 25 December 2010 Accepted 17 July 2011 DOI:10.1111/j.1478-3231.2011.02625.x 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 hepa- tobiliary 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 com- pared 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 hepatobil- iary transport systems in the development of post-operative hyper bilirubin- emia is not yet completely understood, this study provides new insights into the molecular aspects of post-operative jaundice after liver surgery. Liver resections for colorectal metastasis can nowa- days be performed safely with low mortality and morbidity rates in specialized high-volume liver cen- tres. However, up to 75% of patients undergoing abdominal surgery develop abnormal liver chemistry tests post-operatively (1,2). Various factors may be responsible for the development of post-operative jaundice including intra-operative blood loss with consecutive blood transfusions, post-operative haema- toma, parenteral nutrition, anaesthetic agents and medications (e.g. antibiotics, analgetics), sepsis and oxidative stress (3–6). Particularly, intermittent occlusion of blood hepatic inflow to control bleeding during liver surgery (Pringle manoeuvre) results in an ischaemic reperfusion (IR) injury and hyperbilirubinaemia and elevations of liver enzymes are common (7,8). Severe post-operative jaundice, however, is rare in patients without preexist- Liver International (2011) © 2011 John Wiley & Sons A/S 1 Liver International ISSN 1478-3223