Liver Function Test (Ninija Nerd)

• Liver function test (LFT)


  Also known as liver biochemical tests, they indicate hepatic function and liver injury
• LFTs can give a basic concept of hepatic function but also indicate liver injury
• LFTs


  • Indicate evidence of hepatocellular injury
  • Indicate evidence of biliary injury
  • Indicate abnormalities in bilirubin levels
• Hepatocellular injury


  Damaged hepatocytes leak enzymes like AST and ALT into the bloodstream
• Biliary injury


  1. Obstruction or damage to bile ducts leads to elevated alkaline phosphatase and GGT

  2. Bilirubin builds up and enters the bloodstream
• Unconjugated hyperbilirubinemia


  Elevated levels of unconjugated (indirect) bilirubin in the blood
• Conjugated hyperbilirubinemia


  Elevated levels of conjugated (direct) bilirubin in the blood
• Mixed hyperbilirubinemia


  Elevated levels of both unconjugated and conjugated bilirubin
• Decreased liver function


  • Decreased production of albumin
  • Decreased production of clotting factors
• Decreased albumin production


  • Decreased oncotic pressure
  • Fluid leakage into pleural and peritoneal spaces
  • Pitting edema
• Decreased clotting factor production


  Increased risk of bleeding
• Clotting proteins


  Factor 2, Factor 7, Factor 9, Factor 10, Antithrombin 3, Protein C, Protein S
• Clotting proteins


  • Procoagulants
  • Anticoagulants
• In liver disease


  Decreased number of procoagulants and anticoagulants
• Decreased procoagulants


  Increased risk of bleeding (coagulopathy)
• PT INR


  Lab value dependent on Factor 7, indicates ability to clot
• In liver failure, PT INR >1.5 indicates inability to properly clot
• Symptoms of coagulopathy include mucocutaneous bleeds, intracranial hemorrhages, GI bleeds
• Thrombocytopenia


  Decreased number of platelets, worsens coagulopathy
• Liver also produces thrombopoietin, which tells bone marrow to make platelets
• Ammonia


  Marker of liver injury/dysfunction, elevated in liver failure
• Bilirubin


  Marker of liver injury and function, elevated due to inability to conjugate/excrete
• Key tests for liver dysfunction: PT INR, risk of coagulopathy, low albumin
• Other historical tests like ammonia, bilirubin challenges are no longer done due to ethical concerns
• Acute, massive elevation (>1000) of AST/ALT suggests drug-induced liver injury, vascular causes, viral hepatitis, or autoimmune hepatitis
• Chronic, lower-level elevation of AST/ALT suggests alcohol-related liver disease, metabolic liver diseases, or chronic viral hepatitis
• AST:ALT ratio >2 suggests alcohol-related liver disease
• Metabolic liver diseases like Wilson's, hemochromatosis, and NAFLD do not typically present with acute, massive AST/ALT elevations
• Vascular causes of acute liver injury include ischemic hepatitis (shock) and Budd-Chiari syndrome (venous outflow obstruction)
• Drug-induced liver injury, especially from acetaminophen toxicity, is a major cause of acute, massive AST/ALT elevation
• Chronic alcohol use and NAFLD can cause a flip in the AST:ALT ratio compared to other liver diseases
• Elevated iron


  Associated with metabolic syndrome
• Elevated copper


  Associated with metabolic syndrome
• Decreasing levels of alpha 1


  Associated with metabolic syndrome
• Features of metabolic syndrome


  • Obesity
  • Slowly elevated glucose levels due to insulin resistance
  • Hypertension
  • Dyslipidemia
  • Non-alcoholic fatty liver disease
• Non-alcoholic fatty liver disease


  Ratio of ALT to AST is flipped compared to alcoholic fatty liver disease
• Things to remember besides metabolic diseases

  • Autoimmune hepatitis
• Autoimmune hepatitis


  Doesn't often cause obvious presentations, may have other autoimmune diseases, massive elevation in liver enzymes
• Antibodies to test for in autoimmune hepatitis


  • ANA
  • Anti-smooth muscle antibody
  • Anti-LKM1 antibody
• Things to consider in differential diagnosis


  • Drugs
  • Metabolic diseases
  • Biliary obstruction