Total Serum Bile Acid as a Potential Marker for the Diagnosis of Cholangiocarcinoma without Jaundice

Abstract

Diagnosis of cholangiocarcinoma (CCA) is difficult when patients do not show jaundice. The aim of this study was to examine the feasibility of using the total serum bile acid (TSBA) level as an aid for the diagnosis of CCA in patients without jaundice. For this purpose, TSBA of the following groups were measured using a Beckman Synchron CX4 clinical chemistry analyzer: 60 cases of CCA with total serum bilirubin ≤2 mg/dL (low total bilirubin group, LTB); 32 cases of CCA with total serum bilirubin >2 mg/dL (high total bilirubin group, HTB); and 115 healthy controls. Liver function parameters such as serum cholesterol, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were also examined. The results showed that the TSBA of both LTB and HTB groups of the CCA patients were significantly higher than that of the healthy controls. Also, significant correlation was observed between TSBA and total bilirubin levels in the HTB group of CCA patients. However, no such correlation was seen in the LTB group. The cut-off value of TSBA was determined for the LTB group of CCA patients using the receiver operating characteristic curve analysis, and it was 6.05 µmol/L with the sensitivity and specificity of 46.7% and 84.4%, respectively. In addition, the ALP level was correlated well with the TSBA level and ALP in HTB group was significantly higher than that of LTB group. Moreover, the combination of high TSBA and high ALP levels gave higher specificity up to 97.4%. TSBA might be useful for the diagnosis of CCA patients without jaundice.

Serum Metabolites as Diagnostic Biomarkers for Cholangiocarcinoma, Hepatocellular Carcinoma, and Primary Sclerosing Cholangitis

“…However, obstructive cholestasis may occur depending on the localization of tumors, and high serum levels of bile acids can be found in some patients with iCCA. (31) Interestingly, increased levels of cholesterol and 38 glycerophospholipids, mainly phosphatidylcholines and lysophosphatidylcholines, in the serum of patients with PSC were found to be unaltered in patients with iCCA. Phosphatidylcholine species are important components of bile, playing a key role in the formation of mixed micelles of bile acids and cholesterol, and protecting cholangiocytes from the harmful detergent properties of bile acids.…”

“…Here, we found elevated levels of primary bile acids in PSC compared with iCCA. However, obstructive cholestasis may occur depending on the localization of tumors, and high serum levels of bile acids can be found in some patients with iCCA . Interestingly, increased levels of cholesterol and 38 glycerophospholipids, mainly phosphatidylcholines and lysophosphatidylcholines, in the serum of patients with PSC were found to be unaltered in patients with iCCA.…”

Serum pyruvate dehydrogenase kinase as a prognostic marker for cholangiocarcinoma

“…Nevertheless, when the correlation of the PDK3 intensity and clinical parameters of patients was analyzed, a significant correlation was observed between PDK3 and three CCA biomarkers, namely, ALP, total bilirubin and direct bilirubin. Our previous studies revealed that, in CCA, the total serum bile acid correlates with total bilirubin, and total serum bile acid and intercellular adhesion molecule 1 correlate with ALP (23,24). Although the possible mechanisms underlying this phenomenon remain unclear, an inverse correlation between the PDK3 level and survival times was observed.…”

Nomograms incorporated serum direct bilirubin level for predicting prognosis in stages II and III colorectal cancer after radical resection

“…In fact, cut-off values of DBIL vary in different studies. For example, Gao et al [ 8 ] used the thresholds 2.6 μmol/l as cutoff to classified the DBIL, while Li et al [ 14 ] adopted 3.45 μmol/l as optimal cutoff in non-small-cell lung cancer, which value is quite close to our present study.It should be noted that in some studies used TBIL as main concern for survival analysis [ 15 , 16 , 21 ].TBIL consists of both DBIL and IDBIL, which may cause confuse.…”