Biliary lipid compositions of children with PFIC and AGS remain poorly understood, and these data demonstrate that they differ according to disease. The biliary lipid composition of AGS patients was essentially normal, whereas bile from PFIC patients contained minimal biliary lipids. This likely reflects the differing pathophysiology of the diseases. The bile from PFIC patients with FIC1 genotype and BSEP genotype both had very low lipid concentrations but were not significantly different from each other. This may reflect similar mechanisms of cholestasis in both types of low-GGT PFIC, with a primary impairment of transporter expression and function. It should be noted that this study examined lipid concentrations in bile, rather than secretion rates. In addition, pre-PEBD bile was obtained from the gallbladder, while post-PEBD bile was obtained from the stoma.
After clinically successful PEBD, the bile composition of FIC1 patients had a four-fold increase in phospholipid content without changes in bile salts or cholesterol. The bile remained relatively normal in AGS patients and no significant changes were noted in BSEP patients. Lipid content of all PFIC patients who responded to PEBD demonstrated a trend to increased bile salt, cholesterol and CDCA/CA content after PEBD, although these did not reach statistical significance. There were a limited number of patients with these rare diseases and significant variability between the human subjects, so one cannot exclude the possibility that increases in the concentrations of these lipids could not be detected in this study. Also, given that there was significant homogeneity in the FIC1 patients who shared the same mutation compared to the BSEP patients who were unrelated with distinct mutations, it is possible that the specific mutation in the FIC1 patients may intrinsically be associated with a milder disease and more favorable outcome in this study. We were unable to identify any other parameters such as age at diversion, histological stage or liver function levels before diversion that served as prognostic indicators for success in PFIC patients undergoing PEBD.
Baseline bile lipid content at PEBD differed in composition between AGS patients and PFIC patients; differences likely reflecting differences in the etiology of cholestasis . In AGS, the paucity of interlobular bile ducts (fewer than 0.4 bile ducts per portal area)  is believed to underlie cholestasis by causing obstruction of biliary drainage. Sixty to eighty percent of hepatic lobules lack biliary drainage while remaining capable of producing bile, more in the periphery than the core . AGS patients have serum values characteristic of biliary obstruction with markedly elevated serum cholesterol, bile salts, and lipoprotein-X values, presumably due to reflux of bile constituents from canaliculi and ductules with inadequate bile drainage [26–28]. Our findings suggest that patients with AGS make normal bile similar to that reported for normal children . Thus, it appears that cholestasis in AGS is due to excreting too little "normal bile" or retaining too much. The ability of AGS patients' hepatocytes to make and secrete bile may protect them from cellular cholestasis and cholate injury, and provides a putative explanation why progressive liver disease is relatively uncommon .
Compared to AGS bile, PFIC bile contains very low concentrations of lipid. This finding reflects the functions of the PFIC gene products, FIC1 and BSEP, which are pivotal in canalicular bile formation. The potentially resultant effect on PFIC serum levels is a relatively lower cholesterol concentration and absence of lipoprotein-X [31, 32]. The low molar ratio of CDCA/CA in PFIC bile likely reflects the relatively poor excretion of hydrophobic bile salts [7, 33], which is evidenced by the preponderance of CDCA in the serum of these patients [4, 34, 35], although a causative relationship remains speculative.
The bile composition of AGS patients does not change after successful PEBD. Dramatically lower serum cholesterol values in AGS patients after successful PEBD  probably reflect shunting of cholesterol to bile acid synthesis, similar to the effect of oral bile acid binding resins on serum cholesterol in hypercholesterolemia . In AGS, PEBD may simply shunt bile away from the enterohepatic circulation, without fundamentally changing primary hepatobiliary function.