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

The aim of this work was to investigate the reappearance during liver neopl asia of bile acids (BAs) species, which are unusual in healthy adults, but common in fetuses. Serum and urine samples were collected from patients wit h hepatocellular carcinoma (HCC; n = 27), and for comparative purposes, wit h liver cirrhosis (n = 49), liver metastasis (n = 19), chronic viral hepati tis (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 ch enodeoxycholate/cholate ratio in both serum and urine. Although increased l evels of BAs, with hydroxylations at unusual positions, and oxo-BAs were fo und in HCC, these were not significantly different from those observed in o ther 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, w ere markedly increased in the serum and urine of HCC patients. They were al so detected, although in much lower amounts, in liver metastasis and liver cirrhosis, but not in viral hepatitis. Flat-BAs were better detected in uri ne than in serum. Urinary Delta (4)-unsaturated-BA output was significantly lower in patients with small tumours (< 3 cm) compared with those with hig her size tumours. No correlation between flat-BA output into urine and seru m alphafetoprotein 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.