What is the management of conjugated hyperbilirubinemia in adults?

From the Guidelines

The management of conjugated hyperbilirubinemia in adults should start with a right upper quadrant US to confirm an obstructive process and localize the site of obstruction, as recommended by the American College of Radiology 1. The initial step in managing conjugated hyperbilirubinemia is to identify the underlying cause, which can be achieved through a combination of liver function tests, imaging studies, and possibly liver biopsy.

• The differential diagnosis of jaundice due to biliary obstruction in adults includes intrinsic and extrinsic tumors, choledocholithiasis, primary sclerosing cholangitis, parasitic infections, lymphoma, AIDS cholangiopathy, acute and chronic pancreatitis, and strictures after invasive procedures 1.
• For obstructive causes like gallstones or tumors, endoscopic retrograde cholangiopancreatography (ERCP) may be needed for stone removal or stent placement, with surgical intervention sometimes required.
• In drug-induced cases, the offending medication should be discontinued immediately.
• For infectious causes like hepatitis, specific antiviral treatments may be indicated, such as entecavir or tenofovir for hepatitis B, or direct-acting antivirals for hepatitis C based on genotype.
• Supportive measures include nutritional support, vitamin K supplementation for coagulopathy, and management of complications like pruritus with cholestyramine.
• The American Gastroenterological Association recommends that elective radiologic and serologic evaluations should be dependent on the clinical scenario specific to an individual patient 1.
• In patients with significant symptoms, evidence of chronic or decompensated liver disease, or severe liver chemistry abnormalities, a complete and expeditious evaluation is essential, which may include computerized tomography or abdominal magnetic resonance imaging 1.
• Ursodeoxycholic acid at 13-15mg/kg/day is beneficial for primary biliary cholangitis, and autoimmune hepatitis typically requires immunosuppression with prednisone and azathioprine.
• In severe cases with liver failure, liver transplantation evaluation should be considered.
• The management approach targets the pathophysiological mechanisms disrupting bilirubin metabolism and excretion, aiming to restore normal liver function and prevent progressive liver damage.

From the Research

Causes of Conjugated Hyperbilirubinemia

• Conjugated hyperbilirubinemia can be caused by generalized hepatocellular injury, selective cholestatic defects, biliary obstruction, or genetic disorders of bilirubin transport 2
• It can also occur in disorders of hepatocellular damage, such as viral and alcoholic hepatitis, and cholestatic disorders, such as choledocholithiasis and neoplastic obstruction of the biliary tree 3
• Inherited non-hemolytic conjugated hyperbilirubinemic conditions include Dubin-Johnson syndrome and Rotor syndrome, which are caused by mutations affecting specific genes 4

Evaluation and Management

• The evaluation of jaundice in adults relies on history and physical examination, and initial laboratory evaluation should include fractionated bilirubin, complete blood count, and liver function tests 3
• Imaging with ultrasonography or computed tomography can help differentiate between extrahepatic obstructive and intrahepatic parenchymal disorders 3
• Management of conjugated hyperbilirubinemia depends on the underlying cause, and may require modification of antiviral drug choice or dose in cases of liver injury or hemolysis 2
• In some cases, severe hyperbilirubinemia can herald a high risk for death or need for liver transplantation, especially in patients with reduced hepatic reserve 5

Specific Conditions

• Dubin-Johnson syndrome and Rotor syndrome are benign inheritable disorders of bilirubin metabolism that can cause conjugated hyperbilirubinemia, but may also increase susceptibility to drug toxicity 4
• Severe hyperbilirubinemia after creation of transjugular intrahepatic portosystemic shunts (TIPS) is associated with a high risk of death or need for liver transplantation, and predictors of hyperbilirubinemia include nonalcoholic causes of liver disease and prolonged prothrombin time 5