Studies on the mechanism of fasting hyperbilirubinemia.

Abstract

The total plasma bilirubin concentration (Br) increased by 23 to 334% in 12 individuals (10 healthy volunteers and 2 patients with Gilbert’s syndrome) who fasted for 1 to 3 days. Eighty-six per cent of the rise in Br was due to an increase in plasma unconjugated bilirubin. The percentage increase in Br did not correlate with the magnitude of the base line concentration. Studies with bilirubin-3H in 5 subjects showed that the hepatic clearance of bilirubin from the plasma (CBr) was reduced by 28 to 54% during fasting, accounting for the increase in Br. The ratio of the plasma bilirubin turnover during fasting to that in base line state was 0.99 ± 0.16 (mean ± sd ) for these five individuals, indicating that increased plasma bilirubin turnover did not contribute to the rise in Br. In 5 additional subjects the mean change in carbon monoxide production with fasting was only + 24%, whereas Br increased by 188%. Further studies were done to determine why CBr decreases with fasting. The plasma disappearance rate of indocyanine green in 5 subjects after a 48-hr fast was unchanged from base line. Nine homozygous Gunn rats had a 41 ± 10% (mean ± se ) increase in Br over control values with 48 hr of fasting. Bilirubin-3H clearance studies in 2 homozygous Gunn rats demonstrated 43 and 44% decreases in the whole body clearance of bilirubin during fasting, with return to control rates on refeeding. Multicompartmental analysis of the human bilirubin clearance data showed that the ratio of the hepatic bilirubin pool to plasma bilirubin pool decreased during fasting. These results are most consistent with the hypothesis that CBr decreases with fasting because of reduced hepatic ability to extract bilirubin from the plasma.