Increased levels of typically fetal bile acid species in patients with hepatocellular carcinoma

Abstract

The aim of this work was to investigate the reappearance during liver neoplasia of bile acids (BAs) species, which are unusual in healthy adults, but common in fetuses. Serum and urine samples were collected from patients with hepatocellular carcinoma (HCC; n=27), and for comparative purposes, with liver cirrhosis (n=49), liver metastasis (n=19), chronic viral hepatitis (n=11) and healthy volunteer (control group; n=26) groups. BAs were identified and measured by GC--MS. Hypercholanaemia was found in all groups of patients. In HCC, this was characterized by a marked increase in the chenodeoxycholate/cholate ratio in both serum and urine. Although increased levels of BAs, with hydroxylations at unusual positions, and oxo-BAs were found in HCC, these were not significantly different from those observed in other groups. However, BAs with a flat structure, i.e. Delta(4)-unsaturated- and 5 alpha- or allo-BAs, which were almost absent in healthy subjects, were markedly increased in the serum and urine of HCC patients. They were also detected, although in much lower amounts, in liver metastasis and liver cirrhosis, but not in viral hepatitis. Flat-BAs were better detected in urine than in serum. Urinary Delta(4)-unsaturated-BA output was significantly lower in patients with small tumours (<3 cm) compared with those with higher size tumours. No correlation between flat-BA output into urine and serum alpha-fetoprotein or total BAs was found. These results suggest that Delta(4)- and/or allo-BAs are particularly elevated in patients with HCC, which may be a potentially useful complementary, rather than alternative, marker for early detection of liver neoplasia.

Relationship between asymptomatic hypercholanaemia of pregnancy and progesterone metabolism

“…see [29]) we have found normal serum total BA concentrations after an overnight fasting period to be lower than 6 µM when assays were carried out using enzymic techniques, and lower than 10 µM when using more sensitive GC-MS Intrahepatic cholestasis of pregnancy analysis. Thus the results obtained at the end of each trimester of gestation were divided on the basis of a serum 3α-hydroxy-BA concentration cut-off value of 6 µM (see Figure 1).…”

Potential role of trans-inhibition of the bile salt export pump by progesterone metabolites in the etiopathogenesis of intrahepatic cholestasis of pregnancy

“…The amount of PM4 was measured without previous desulfation of the sample and that of PM4-S was calculated from the difference between the analyses carried out with and without desulfation of the sample. GC-MS was also used to measure progesterone and E 2 17bG after enzymatic deglucuronidation [19].…”

“…The concentration of 3a-hydroxyl-BAs in bile was measured enzymatically [17]. After being desulfated [18] and derivatized, total PM4 (PM4 plus PM4-S) in bile was measured by gas-liquid chromatography coupled to mass spectrometry (GC-MS) [19]. The amount of PM4 was measured without previous desulfation of the sample and that of PM4-S was calculated from the difference between the analyses carried out with and without desulfation of the sample.…”

Changes in the expression of genes related to bile acid synthesis and transport by the rat liver during hepatocarcinogenesis

“…Phenotypic changes affecting the presence and amount of BA species in the BA pool during hepatocarcinogenesis may be of pathophysiological and diagnostic/prognostic relevance [3]. Unlike major BAs, some minor BAs, including allo-BAs and 4 -unsaturated BAs, have a 'flat' structure of the steroid nucleus, similar to that of steroid hormones.…”