Imre Magyar - Metabolism of bile acids

As bile acids are produced from cholesterol, changes in their metabolism are mainly related to changes in cholesterol metabolism. In hypercholesterolaemia, usually hyperlipoproteinaemia, especially familial hypercholesterolaemia, bile acid excretion is substantially reduced, deoxycholic acid is barely detectable in the blood and the amount of secondary bile acids in the faeces is also reduced.
However, this may also be due to the rapid absorption of primary bile acids and the reduced production of secondary bile acids [22, 23, 585].
In liver disease, blood bile acid levels usually increase, but the increase is not proportional to the severity of the liver disease.
In our experiments [362, 548], we found that only concentrations of bile acids above 2.5 μmol/1 were a definite indicator of liver disease and that normal bile acid levels were found in a significant proportion of liver diseases. The concentration of kenodeoxycholic acid is normally higher than that of cholic acid. We have found that if the cholic acid/kenodeoxycholic acid ratio is greater than l, there is a high probability of cholestasis, in diffuse liver diseases the excretion of bile acids in the faeces is also reduced, but within the reduction, the amount of lithocholic acid is increased [847].
In acute hepatitis, bile acid synthesis is reduced and bile acid secretion is decreased. The reduced clearance results in increased bile acid levels in the blood, but also because bile acids absorbed from the intestine are not reabsorbed into the enterohepatic circulation due to liver dysfunction. Blood bile acids are particularly high in obstructive jaundice. We ourselves have found the highest values in primary biliary cirrhosis [548]. Bile acids that are carried by the circulation to the skin may be the cause of the excruciating itching that is a symptom of both extrahepatic and intrahepatic cholestasis.
In cholestasis, the amount of sulphate ese acids excreted in the urine is also strikingly high.
In principle, therefore, it is worthwhile to perform bile acid determinations in the blood and urine, and possibly in the faeces, of liver patients [49, 118], but it seems that, except in a few specific cases, the examination of fasting bile acid in the blood does not provide new information. For this reason, and because of technical difficulties, the determination of bile acids is difficult to enter the everyday clinical practice. Bile acid metabolism is also influenced by absorption. Thus, in malabsorption, the absorption of bile acids is reduced and a higher amount of secondary bile acids is produced. Of these, lithocholic acid is thought to play a role in the development of some diarrhoea.
Unfortunately, the metabolism of bile acids is influenced by too many factors and this makes it difficult to assess. Loading assays have been developed in the form of post-meal bile acid determinations [245, 414, 548, 787]. We ourselves [362] performed oral kenodeoxycholic acid loading. We have found that individual or whole blood bile acids in healthy individuals increase in one hour and decrease in two hours, but in liver disease the increase lasts beyond two hours. An intravenous assay has also been developed [477].
Bile acids, of course, play a major role in keeping bile cholesterol in solution and thus in the formation of bile. The primary cause of cholesterol stone formation appears to be a reduction in the bile acid pool.
Bile acids have an important role in the absorption of fats and, as mentioned above, the causes of diarrhoea include the accumulation of secondary bile acids in the intestine under certain circumstances (e.g. after intestinal resection, ileotransversostomy, etc.).