Bile acids analysis: a tool to assess graft function in human liver transplantation

Abstract

The expanding use of “sub‐optimal” grafts due to donor organ shortage increases the importance of accurate graft assessment before liver transplantation. Bile secretion is an early sign of recovering hepatic function post‐transplant. The role of bile acid analysis in assessing graft function before and immediately after liver transplantation has been investigated. Two hundred and sixteen samples of hepatic bile were collected from 35 donors and 13 recipients. Clinical data, bile flow, total bile acid concentration, apparent choleretic activity and bile acid composition were assessed. Sub‐optimal donor livers showed a low apparent choleretic activity and a different bile acid composition when compared to normal grafts. In recipients, the pattern of recovery of bile secretion immediately after reperfusion was a useful predictor of graft function. This study characterises bile acid secretion of liver grafts and remarks the potential value of bile acid analysis to assess donor liver quality and early post‐transplant graft function.

Bile Composition as a Diagnostic and Prognostic Tool in Liver Transplantation

“…(41) A couple of years later, the same group showed that suboptimal donor livers had a different bile acid composition compared with standard grafts: a lower apparent choleretic activity (indicating that bile flow did not increase appropriately with increased bile acid output) and a lower ratio of CA/CDCA. (10) Increasing CA/CDCA ratios were observed after recovery from ischemia after LT. (34) Instead of graft assessment during machine perfusion, bile collected during procurement may have the potential to assess liver quality in DBD donors. However, studies on donor bile composition are currently limited, probably due to logistical challenges during procurement.…”

“…When conjugated bile acids enter the canaliculus, ). (10) In humans, up to 90% of bile flow is dependent on bile salts. Bile saltindependent bile flow can be stimulated by active solutes, such as glutathione and bicarbonate.…”

“…(51,52) In a porcine LT model, it was shown that a lower bile/perfusate glucose ratio (<0.6) and a higher bile/ perfusate sodium ratio (≥1.2) during NMP was observed in DBD donors or donors with short warm ischemia (up to 70 minutes) compared with donors with long warm ischemia (120 minutes). (13) Bile composition of rat livers assessed during NMP also Gaurav et al (12) Na and bile glucose-blood glucose Blood gas -/100 NAS Linares-Cervantes et al (13) Bile/perfusate glucose ratio Blood gas 20/-Bile duct viability Bile/perfusate Na ratio Blood gas Matton et al (2) Bicarbonate, pH, and glucose Blood gas -/23 Bile duct injury/NAS Bile/perfusate ratio Blood gas Sutton et al (14) Bilirubin and bicarbonate Blood gas -/12 Bile duct viability de Vries et al (15) pH Blood gas -/7 Bile duct viability Afford et al (16) * pH Unknown 31/-ITBL Habib et al (17) Bile (10) Choleretic activity HPLC -/35 PGD CA/CDCA ratio HPLC Xu et al (21) Bile salts, phospholipids, and cholesterol Spectrophotometry, ELISA 18/-Graft function Ko et al (22) Phospholipids HPLC -/17 Graft function Baumgartner et al (23) Bile acids, phospholipids, and cholesterol Not known -/12 Early graft dysfunction Sánchez-Bueno et al (24) Bile acids, phospholipids, and cholesterol Spectrophotometry -/25 ACR/PNF Chan et al (25) Bile salts ELISA 16/-Early graft dysfunction…”

Future clinical applications of bile analysis

“…Studies where bile was analysed in detail greatly contributed to the understanding of the various aspects of OLTx per se as well as influences of immunosuppressive drugs/regimens, rejection, post‐operative complications and external biliary drainage (T‐tube). Suboptimal donor livers demonstrate an altered bile composition compared with normal grafts 11 . Immediately after transplantation, modifications of bile composition and volume depend on the duration and recovery from cold ischaemia (1–3 h), 12 while acute rejection 13 or immunosuppressive drugs 13 exert their effect later (7–14 days and 3–4 weeks, respectively).…”

Bile Changes after Liver Surgery: Experimental and Clinical Lessons for Future Applications

“…Such modifications in bile composition are probably due to the influence of immunosuppressive drugs [28,29] . Both experimental [26,[29][30][31] and clinical studies [32][33][34] bile acid composition when compared to normal grafts [35] . Bile cytotoxicity (measured by an increase in the bile salt/phospholipid ratio) appears to be involved in the pathogenesis of non-anastomotic biliary strictures [36,37] .…”