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

AbstractBackground and aims: Post-operative hyperbilirubinaemia in patientsundergoing 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 transportsystems in the pathogenesis of post-operative jaundice in humans after liverresection. Methods: Two liver tissue samples were taken from 14 patientsundergoing liver resection before and after Pringle manoeuvre. Patients wereretrospectively divided into two groups according to post-operative bilirubinserum levels. The two groups were analysed comparing the results of hepa-tobiliary transporter [Na-taurocholate cotransporter (NTCP); multidrugresistance 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-operativeliver chemistry tests. Results: Patients with low post-operative bilirubin hadlower levels of NTCP, MDR3 and BSEP mRNA compared to those with highbilirubin after Pringle manoeuvre. HSP70 levels were significantly higherafter ischaemia–reperfusion (IR) injury in both groups resulting in 4.5-foldmedian increase. Baseline median mRNA expression of all four transportersprior to Pringle manoeuvre tended to be lower in the low bilirubin groupwhereas expression of HSP70 was higher in the low bilirubin group com-pared to the high bilirubin group. Discussion: Higher mRNA levels ofHSP70 in the low bilirubin group could indicate a possible protective effectof 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 intothe molecular aspects of post-operative jaundice after liver surgery.Liver resections for colorectal metastasis can nowa-days be performed safely with low mortality andmorbidity rates in specialized high-volume liver cen-tres. However, up to 75% of patients undergoingabdominal surgery develop abnormal liver chemistrytests post-operatively (1,2). Various factors may beresponsible for the development of post-operativejaundice including intra-operative blood loss withconsecutive blood transfusions, post-operative haema-toma, parenteral nutrition, anaesthetic agents andmedications (e.g. antibiotics, analgetics), sepsis andoxidative stress (3–6).Particularly, intermittent occlusion of blood hepaticinflow to control bleeding during liver surgery (Pringlemanoeuvre) results in an ischaemic reperfusion (IR)injury and hyperbilirubinaemia and elevations of liverenzymes are common (7,8). Severe post-operativejaundice, however, is rare in patients without preexist-