Partial liver resection alters the bile salt-FGF19 axis in patients with perihilar cholangiocarcinoma: implications for liver regeneration

Background & Aims Extended liver resection is the only treatment option for perihilar cholangiocarcinoma (pCCA). Bile salts and the gut hormone FGF19, both promoters of liver regeneration (LR), have not been investigated in patients undergoing resection for pCCA. We aimed to study the bile salt-FGF19 axis perioperatively in pCCA and study its effects on LR.

Methods Plasma bile salts, FGF19, and C4 (bile salt synthesis marker) were assessed in patients with pCCA and controls (colorectal liver metastases) before and after resection on postoperative days (POD) 1, 3 and 7. Hepatic bile salts were studied using intraoperative liver biopsies.

Results Partial liver resection in pCCA elicited a sharp decline in bile salt and FGF19 plasma levels on POD 1 and remained low thereafter, unlike in controls, where bile salts rose gradually. Preoperatively, suppressed C4 in pCCA normalized postoperatively to levels similar to those in the controls. The remnant liver volume and postoperative bilirubin levels were negatively associated with postoperative C4 levels. Furthermore, patients who developed postoperative liver failure had nearly undetectable C4 levels on POD 7. Hepatic bile salts strongly predicted hyperbilirubinemia on POD 7 in both groups. Finally, systemic bile salts and FGF19 were not associated with LR in patients with pCCA, as opposed to a positive association between postoperative bile salts and LR in controls.

Conclusions Partial liver resection alters the bile salt-FGF19 axis, and its derailment is unrelated to LR in pCCA. Postoperative monitoring of circulating bile salts and their production may be useful for monitoring LR.

Publication History

Article published online:
23 January 2024