Evidence against a role of serotonin in liver regeneration in humans
Authors: Edris M. Alkozai, Martijn van Faassen, Ido P. Kema, Robert J. Porte, Ton Lisman
Journal: Hepatology (2014)

This study was sponsored, in part, by a Mozaiek grant from the Dutch Organization of Scientific Research awarded to Edris Alkozai. Potential conflict of interest: Nothing to report. Author names in bold designate shared co‐first authorship. To the Editor: We read with great interest the article by Starlinger et al., in which evidence for a role of serotonin in liver regeneration in humans was provided.1 We would like to report on our findings in a prospective study on serotonin levels in platelet‐rich plasma in adult patients undergoing a (extended) right hemihepatectomy (n = 16) in comparison to levels in patients undergoing a pylorus‐preserving pancreaticoduodenectomy (PPPD; n = 10) and healthy controls (n = 22). Patient characteristics were published elsewhere.2 We drew blood samples after induction of anesthesia, at the end of the surgery, and at postoperative days 1, 3, 5, 7, and 30. In addition, we took blood samples from the portal and from the hepatic vein just before the start and just after completion of parenchymal transection in the patients undergoing a hemihepatectomy. Serotonin levels in platelet‐rich plasma were determined by liquid chromatography/tandem mass spectrometry, and levels were corrected for platelet count. The study protocol was approved by the local medical ethical committee, and informed consent was obtained from each participant before inclusion in the study. Serotonin levels at baseline were comparable between patients undergoing hemihepatectomy, patients undergoing PPPD, and healthy subjects (Fig. 1). In contrast to the Starlinger et al. study, no changes in serotonin were observed in the early postoperative period. Only at postoperative days 5 and 7 had serotonin levels clearly decreased; but, importantly, the decrease was similar between the hemihepatectomy and PPPD patients. Serotonin content was identical between samples taken in the afferent and efferent liver veins before and after hemihepatectomy, indicating that there was no detectable serotonin consumption by the liver directly after hemihepatectomy. Although the number of patients we studied was smaller compared to the Starlinger study, we studied more time points in a more homogeneous cohort consisting of patients without cirrhosis undergoing a major hepatectomy, included an appropriate control group, and studied the serotonin gradient over the liver before and just after hemihepatectomy. Technical differences between the studies included measurement of serotonin in platelet‐rich plasma versus a calculated serum‐platelet–poor plasma difference, as studied by Starlinger et al. Importantly, we calculated serotonin content per platelet, thereby correcting for consumption of platelets as a result of dilution or consumption.Figure 1: Median serotonin levels in controls, patients undergoing hemihepatectomy, and patients undergoing PPPD. Shown are serotonin levels corrected for platelet count. *P < 0.05 versus pre‐op (Friedman's test). +P < 0.05, hemihepatectomy versus PPPD (Mann‐Whitney's U test). Abbreviations: End‐OK, end of surgery; HH, hemihepatectomy; HV, hepatic vein; POD, postoperative day; Pre‐OP, preoperative; VP, vena porta.Although we do not dispute that platelets are likely important for liver regeneration in humans,3 our data do not support the notion that platelet serotonin is key in this process.