Significance of Altered Bilirubin Subfractions in Bile Following Hepatectomy

Abstract

Background. Hyperbilirubinemia occurs as a sign of hepatic failure after hepatectomy. The pathogenesis of this event has not been elucidated. In cases complicated with postoperative infection, hyperbilirubinemia is prolonged and the composition of bilirubin subfractions in bile changes markedly. A reduction in the proportion of bilirubin diglucuronide (BDG) is especially notable. This study was aimed at clarifying the relationship between infection and biliary bilirubin subfractions, with a view to shedding light on the mechanisms of change.Materials and methods. Rats underwent either laparotomy or partial hepatectomy (Hx). Daily intraperitoneal injections of lipopolysaccharide (LPS) or natural saline were administered for 3 days following surgery. Total serum bilirubin levels and proportions of BDG and bilirubin in bile were measured until Day 5 after the operation. Hepatic levels of UDP-glucuronic acid (UDP-GA), UDP-glucose, NAD+, and total adenine nucleotides (TAN) and activities of UDP-glucuronyltransferase (UDP-GT) and UDP-glucose dehydrogenase were measured on Day 4.Results. In hepatectomized rats treated with LPS (Hx-LPS), total serum bilirubin levels were elevated, biliary bilirubin levels were decreased, and the proportion of biliary BDG was decreased on Day 4. Hepatic levels of UDP-GA, NAD+, and TAN and activities of UDP-GT in Hx-LPS were reduced. In all groups tested, a significant linear correlation between BDG and UDP-GA and between UDP-GA and NAD+ was found.Conclusions. The reduction of UDP-GA might be effected by reduced hepatic levels of NAD+ in endotoxemia following hepatectomy. It is therefore suggested that alterations in biliary bilirubin subfractions might accurately reflect the energy state of the remnant liver following hepatectomy.