Glucuronidated bilirubin: Significantly increased in hepatic encephalopathy

Abstract Bilirubin is produced by the breakdown of hemoglobin in senescent erythrocytes by macrophages and carried by albumin from blood circulation to the liver for removal in normal physiology. Glucuronic acid modification of bilirubin by UDP-glucuronyltransferase in the liver is the key event for its subsequent elimination from human body. Conditions that accelerate the breakdown of erythrocytes may cause an elevated blood level of unconjugated bilirubin whereas the factors affect the glucuronidated bilirubin formation and subsequent elimination may cause decreased or increased blood level of glucuronidated bilirubin, the water soluble “direct bilirubin” measured by clinical blood test. Studies showed that increased total serum bilirubin has a protective effect on cardiovascular and other related diseases, but it is unknown how direct bilirubin levels were related to different diseases. By taking advantage of the data collected in the clinical laboratory of our hospital, the direct bilirubin data from 192,535 patients with 72 clinically defined diseases were compared to that of healthy controls (10,497). Based on the mean, median, and p values, we found that patients with hepatic encephalopathy had the highest serum direct bilirubin level, which resembled acute hepatic encephalopathy caused by increased serum direct bilirubin level in neonates. In contrast, patients with uremia, nephrotic syndrome, and preeclampsia had significantly lower levels of serum direct bilirubin. Taken together, our data revealed that serum direct bilirubin levels were either increased or decreased in a disease-dependent manner. The possible molecular mechanisms of increased direct bilirubin levels in patients suffering hepatic encephalopathy are discussed.