If it is the liver that cannot effectively transfer the indirect bilirubin into bilirubin glucuronide and further into bilirubin di-glucuronide, the consequence will be hyperbilirubinemia or intrahepatic (or hepatocellular) jaundice.
Moreover, the unconjugated hyperbilirubinemia arises in case the components of liver transfer the indirect bilirubin into bilirubin glucuronide in the rate slower than they should be. This condition is associated with either decreased uptake of bilirubin into hepatocytes (Rotor syndrome) or defective intracellular protein binding.
In similar fashion, the conjugated hyperbilirubinemia emerges in case the components of the liver have difficulty turning bilirubin glucuronide into bilirubin di-glucuronide. Note that biliary duct blockage can also lead to conjugated hyperbilirubinemia but the pathophysiology is that backflow of bilirubin di-glucuronide with little indirect bilirubin and bilirubin glucuronide from bile duct through liver into blood plasma. These conditions are associated with either defective intracellular protein binding (for the second time) or disturbed secretion into the bile canaliculi (Dubin–Johnson syndrome).
Liver failure and hepatitis are the most etiological in liver-genesis hyperbilirubinemia. In case of hyperbilirubinemia due to intrahepatic or extrahepatic bile ducts blockage, e.g. gallstone, the name is given as Post-hepatic (or obstructive) jaundice.
Bilirubin concentration is not a sensitive early indicator of liver diseases as the liver may have reserved its capacity in removal of bilirubin to save energy and unreserved the previously reserved capacity when encountering a sudden rise of unconjugated bilirubin. In short, there is still a chance for an ill liver to get rid of excessive unconjugated bilirubin in the blood plasma, displaying a total bilirubin level that is within normal reference range.