title: Evidence for serotonin as a relevant inducer of liver regeneration after liver resection in humans.
abstract: Liver regeneration (LR) involves a complex interplay of growth factors and antagonists. In this context, platelet-derived serotonin (5-HT) has been identified as a critical inducer of LR in mice. Clinical evidence for a role of 5-HT in LR in humans is lacking. Accordingly, serum and plasma 5-HT was monitored perioperatively in 60 patients undergoing liver resection, of which 35 served as exploration and 25 as validation sets. Intraplatelet (IP) levels of 5-HT were calculated by subtraction of plasma 5-HT from serum values. Serum markers of liver function were used to evaluate LR and liver dysfunction (LD). In the exploration setting, IP 5-HT levels significantly decreased after liver resection (P < 0.001) and gradually recovered during the first week. IP 5-HT measured before surgery specifically predicted LD in the subsequent 7 days (area under the curve: 0.721; P = 0.029). Patients suffering from postoperative LD and morbidity were found to have reduced IP 5-HT levels during the entire perioperative period. Furthermore, we validated that reduced preoperative IP 5-HT (<73 ng/mL) was associated with an increased incidence of postoperative LD and morbidity (P = 0.045 and P = 0.021) and were able to demonstrate that IP 5-HT levels were an independent predictor of poor clinical outcome.
  
  
  CONCLUSIONS
  These findings provide evidence that IP 5-HT correlates with LR in humans: Patients with low IP 5-HT before liver resection suffered from delayed hepatic regeneration. Therefore, IP 5-HT levels may prove a helpful clinical marker to predict postoperative LD and clinical outcome before hepatic resection and initiate suitable interventions.
authors.affiliation: Department of Surgery, Medical University of Vienna, General Hospital, Vienna, Austria.
authors.forename: Patrick
authors.initials: P
authors.lastname: Starlinger
authors.forename: Alice
authors.initials: A
authors.lastname: Assinger
authors.forename: Stefanie
authors.initials: S
authors.lastname: Haegele
authors.forename: David
authors.initials: D
authors.lastname: Wanek
authors.forename: Silvia
authors.initials: S
authors.lastname: Zikeli
authors.forename: Dominic
authors.initials: D
authors.lastname: Schauer
authors.forename: Peter
authors.initials: P
authors.lastname: Birner
authors.forename: Edith
authors.initials: E
authors.lastname: Fleischmann
authors.forename: Birgit
authors.initials: B
authors.lastname: Gruenberger
authors.forename: Christine
authors.initials: C
authors.lastname: Brostjan
authors.forename: Thomas
authors.initials: T
authors.lastname: Gruenberger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000601:surgery*; D018281:Cholangiocarcinoma / Q000601:surgery; D015179:Colorectal Neoplasms / Q000556:secondary / Q000601:surgery; D005260:Female; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000601:surgery*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D011184:Postoperative Period; D057234:Preoperative Period; D011446:Prospective Studies; D012701:Serotonin / Q000097:blood / Q000378:metabolism*; D055815:Young Adult
chemical_list: D012701:Serotonin