Elevated cholestatic liver enzymes

Background

• Refers to a rise in ALP and GGT +/- bilirubin that is much more pronounced than any rise in ALT
• ALP can also come from bone and placenta

Differential Diagnosis

Marked Elevation

• ExtrAhepatic biliary obstruction
  • Choledocholithiasis
  • Cancer of the pancreas, gallbladder, ampulla of Vater, biliary duct, or perihilar lymph nodes
  • Biliary strictures
    • Primary sclerosing cholangitis with extrahepatic bile duct stricture
    • Procedural complication of ERCP
    • Chronic pancreatitis resulting in stricture of the distal bile duct
    • Anastomotic stricture of the bile duct after liver transplantation
  • Infection: AIDS cholangiopathy, Ascaris lumbricoides, liver fluke
• Intrahepatic cholestasis
  • Drugs and toxins
  • Primary biliary cholangitis
  • Primary sclerosing cholangitis
  • Intrahepatic cholestasis of pregnancy
  • Benign postoperative cholestasis
  • Total parenteral nutrition
  • Infiltrative diseases: amyloidosis, lymphoma, sarcoidosis, tuberculosis, or hepatic abscess
  • Liver metastases
  • Allograft rejection after liver transplant
  • Alcoholic hepatitis
  • Hepatic crisis of sickle cell disease
  • Others: IgG4 cholangiopathy, ischemic cholangiopathy, COVID-19

Investigations

• Liver/biliary ultrasound to help differentiate between extrahepatic cholestasis (if biliary dilatation is seen) versus intrahepatic
• For intrahepatic cholestasis
  • First order AMA (for PBC), ANA, anti-smooth muscle antibodies
  • Then consider MRCP, hepatitis A, B, C, and E testing, and EBV and CMV testing
  • Finally, consider liver biopsy