Journal of Liver

Comparative Analysis of Bilirubin Metabolism in Different Lobes and Genetic Variants in Liver

Marcin Zimmer^* Department of Internal Medicine, Regent's University London, London, England, United Kingdom
^*Correspondence: Marcin Zimmer, Department of Internal Medicine, Regent's University London, London, England, United Kingdom, Email:

Received: 03-Jul-2023, Manuscript No. JLR-23-22836; Editor assigned: 06-Jul-2023, Pre QC No. JLR-23-22836 (PQ); Reviewed: 19-Jul-2023, QC No. JLR-23-22836; Revised: 26-Jul-2023, Manuscript No. JLR-23-22836 (R); Published: 02-Aug-2023, DOI: 10.35248/2167-0889.23.12.194.

Description

Bilirubin is a yellow pigment that is produced from the breakdown of heme, a component of hemoglobin and other hemoproteins. Bilirubin is mainly formed in the reticuloendothelial system, where macrophages degrade old or damaged red blood cells and release heme. Heme is then converted to biliverdin and then to bilirubin by the enzyme heme oxygenase. Bilirubin is transported in the blood by binding to albumin, a plasma protein, and reaches the liver, where it is taken up by hepatocytes. In the liver, bilirubin undergoes conjugation with glucuronic acid by the enzyme UDP-Glucuronosyltransferase 1A1 (UGT1A1), which makes it more water-soluble and allows it to be excreted into bile. Bile flows from the liver to the gallbladder and then to the small intestine, where bilirubin is further metabolized by intestinal bacteria into urobilinogen and stercobilin. Urobilinogen can be reabsorbed into the blood and excreted by the kidneys as urobilin, or oxidized to stercobilin and eliminated in the feces. The normal range of total serum bilirubin is 0.3 mg/dL to 1.2 mg/dL, of which about 80% is unconjugated and 20% is conjugated. Bilirubin metabolism is a complex process that involves multiple organs and enzymes, and can be affected by various factors such as genetic variations, liver function, bile flow, intestinal flora, and drug interactions. In this article, we will focus on two aspects of bilirubin metabolism that have been studied extensively: the differences between different lobes of the liver in bilirubin uptake and conjugation, and the genetic variants of UGT1A1 that influence bilirubin levels and clinical outcomes.

The liver is divided into four lobes: right, left, caudate, and quadrate. Each lobe has its own blood supply and bile drainage system, and can function independently from the others. However, there are also differences between the lobes in terms of their metabolic activities and functions. One of these differences is related to bilirubin metabolism. Several studies have shown that there is a gradient of bilirubin uptake and conjugation across the liver lobes, with the highest rates in the caudate lobe and the lowest rates in the right lobe. This gradient is maintained even after partial hepatectomy or liver transplantation. The reasons for this gradient are not fully understood, but some possible factors include differences in blood flow, oxygen tension, enzyme expression, transporter activity, and hormonal regulation. The gradient of bilirubin metabolism in the liver lobes has implications for clinical practice. For example, it may affect the interpretation of serum bilirubin levels in patients with liver diseases or after liver surgery. It may also influence the selection of donor livers for transplantation, as different lobes may have different capacities to handle bilirubin load. Furthermore, it may provide insights into the pathophysiology of some liver disorders that are associated with altered bilirubin metabolism, such as Dubin- Johnson syndrome, Rotor syndrome, Crigler-Najjar syndrome, and Gilbert’s syndrome.

Gilbert’s syndrome is one of the most common inherited disorders of bilirubin metabolism, affecting about 5% to 10% of the general population. It is characterized by mild unconjugated hyperbilirubinemia (1.2 mg/dL to 6 mg/dL) that fluctuates with stress, fasting, infection, or menstruation. Gilbert’s syndrome is caused by mutations in the UGT1A1 gene that reduce its activity by about 70%, resulting in impaired conjugation of bilirubin in the liver. The most common mutation is a TA insertion in the promoter region of UGT1A1 (UGT1A1*28), which decreases its transcription. However, there are also other mutations that affect UGT1A1 function or expression. Gilbert’s syndrome is usually asymptomatic and benign, but it can cause cosmetic problems such as jaundice or scleral icterus. It can also interact with drugs that are metabolized by UGT1A1 or compete with bilirubin for albumin binding, such as irinotecan, atazanavir, indinavir, rifampicin, and phenobarbital.

Conclusion

Bilirubin metabolism is a dynamic and intricate process that involves multiple organs and enzymes, and can be influenced by various factors. Understanding the differences between different lobes of the liver in bilirubin uptake and conjugation, and the genetic variants of UGT1A1 that affect bilirubin levels and clinical outcomes, can help us better diagnose and manage patients with hyperbilirubinemia and related disorders. The mechanisms of these effects are not clear, but they may involve the antioxidant, anti-inflammatory, and immunomodulatory properties of bilirubin. Moreover, Gilbert’s syndrome may have protective effects against some diseases, such as cardiovascular disease, gallstones, and cancer.