Bile acid pool size and kinetics were determined in 17 patients with
cirrhosis and 11 patients without
liver disease and correlated with the severity of
liver disease as determined by the usual clinical and laboratory criteria. In order to assess the severity of
liver disease, a grading system was devised which assigned numerical values to various clinical signs and laboratory results. The total clinical score and the patients were divided into two groups of advanced (7-18 points) or mild (1-6 points)
cirrhosis. The clinical rating was then correlated with the various aspects of
bile acid metabolism.
Cholic acid synthesis was markedly reduced in the early stages of
cirrhosis and continued to decrease with the advancement of the
liver disease. There was an inverse correlation between synthesis of
cholic acid and the severity of
cirrhosis. Nine of the 10 patients with advanced
cirrhosis and a very low
cholic acid synthetic rate (average 68 mg per day) died within one to 13 months from the start of the study. Patients with mild
cirrhosis also had significantly reduced
cholic acid synthesis (average 152 mg per day) but they all were well and alive three to 23 months after the study. In contrast,
chenodeoxycholic acid synthesis was not markedly affected in either patients with mild or advanced
cirrhosis. There was also a high degree of correlation between the fractional daily turnover rate of
cholic acid and the severity of
liver disease. The fractional daily turnover rate of
cholic acid was greatly reduced (50%) in patients with advanced
cirrhosis.
Deoxycholic acid was reduced in patients with mild
cirrhosis and virtually absent from the bile of patients with advanced
cirrhosis. The findings of the present report provide evidence that
cholic acid synthesis is a sensitive
indicator of the hepatocellular damage, whereas
chenodeoxycholic acid synthesis is relatively unaffected by
cirrhosis. The selective alteration in
cholic acid synthesis probably resides in a deficiency of one or more
enzymes regulating the formation of the 3-keto, 7 alpha, 12 alpha-dihydroxy precursor of
cholic acid.