Graft bile analysis for predicting post-transplant outcomes: A literature review and a protocol for a novel biomarker

Table 1 Summary of bile biomarkers and clinical significance

Biomarker	Source	Normal range	Abnormal indication	Associated risk	Ref.
Bile pH	Cholangiocytes	> 7.5	A decrease in pH is associated with cholangiocyte injury	ITBL	Watson et al[7]
Bicarbonate	Cholangiocytes	> 18 mmol/L	A decrease in HCO3- is associated with reduced ductal secretion	ITBL	Sasaki et al[19]
Bile glucose	Reabsorbed by ducts	< 1 mmol/L	An increase in glucose is associated with reabsorption failure	Cholangiocyte injury	Watson and Pessin[29]
Lactate	Metabolic stress	< 5 mmol/L	An increase in lactate is associated with anaerobic metabolism	Graft dysfunction	Zhong et al[34]
Bile acids (CA, CDCA, etc)	Hepatocytes/metabolism	Varied	Hydrophobic shift is associated with cytotoxicity	Biliary epithelial apoptosis	Huang et al[10]
Proteins (e.g., IL-6, L-FABP)	Proteomic profiling		An increase in markers is associated with inflammation/apoptosis	Ductal necrosis, inflammation	Junior et al[30]
Lipids (e.g., PC, LPC)	Lipidomics		A decrease in PC and increase in LPC is associated with membrane damage	Biliary leak, ITBL	Zijlstra et al[41]

ITBL: Ischemic type biliary lesion; CA: Cholic acid; CDCA: Chenodeoxycholic acid; IL-6: Interleukine-6; L-FABP: Liver-type fatty acid-binding protein; PC: Phosphatidylcholine; LPC: Lysophosphatidylcholine.

Table 2 Clinical viability criteria using bile during normothermic machine perfusion

Parameter	Threshold	Predictive value	Ref.
Bile production (NMP)	> 30 mL over perfusion	Functional biliary system	de Jong et al[26]
Bile pH	> 7.5	Low risk of cholangiopathy	Watson et al[13]
Bile/perfusate glucose ratio	< 0.67	Preserved glucose reabsorption	Zelger et al[20]
Bicarbonate concentration	> 18 mmol/L	Functional ductal secretion	Ceresa et al[46]
Bile acid hydrophobicity index	Low hydrophobicity	Low risk of epithelial damage	Huang et al[10]

NMP: Normothermic machine perfusion.