Serum levels of cholesterol precursors (squalene, A8-cholestenol, desmosterol and lathosterol), plant sterols (campesterol and sitosterol), cholestanol and cholestanol/noncholesterol sterol ratios were related to liver damage and liver transplantation indications in healthy controls (n = 26) and in 31 patients with primary biliary cirrhosis divided into group I ( Sbilirubin < 21 pmolm n = 14), group I1 (S-bilirubin 21 to 108 pmol/L; n = 7) and group I11 (elected for liver transplantation; S-bilirubin 109 to 520 pmol/L; n = 10). The mean serum respective lathosterol levels in controls and in group I were three and two times higher than those in groups I1 and 111, respectively. The plant sterol contents were higher in group I1 than in groups I and I11 and the campesterol/sitosterol ratios were lowest in group 111. The serum cholestanol levels were high even in group I (i.e., in patients without icterus) and increased progressively to group 111, up to 6 and 13 times those in group I and the control group, respectively. The cholestanol/noncholesterol sterol ratios increased progressively from the controls to groups I, I1 and 111. The serum cholestanol levels were positively related to serum bilirubin levels in all primary biliary cirrhosis patients (n = 31, r = 0.906) and to the plant sterol levels in the control group and group I, but significantly negatively in group 111. The cholestanol vs. precursor sterol correlations were negative in most cases. In conclusion, our findings suggest that determination of serum cholestanol and lathosterol levels and cholestanol/plant sterol, campesterol/sitosterol and campesterolnathosterol ratios might aid staging of liver damage in primary biliary cirrhosis. The high serum cholestanol level associated with the low campesterol/sitosterol ratio could be a significant indicator of end-stage primary biliary cirrhosis and, finally, of the need for liver transplantation. (HEPA-TOLOGY 199 1; 13:663-669.)
Serum levels of cholesterol precursors, particularly methylated sterols and lathosterols, reflect both enhanced and reduced cholesterol synthesis even in man (1-6). The hepatic activity of the rate-limiting enzyme ~