Liver Function Tests

LFT Basics - Liver's Check‑Up Kit

• LFTs (Liver Function Tests): Blood tests assessing liver health & function.
• Purpose:
  • Screening for liver damage.
  • Diagnosing liver diseases.
  • Monitoring disease progression/treatment.
• Categories:
  • Hepatocellular injury (e.g., ALT, AST).
  • Cholestasis (e.g., ALP, GGT, Bilirubin).
  • Synthetic function (e.g., Albumin, Prothrombin Time).

⭐ LFTs can be normal in significant liver disease like compensated cirrhosis.

Injury Markers - Hepatocyte SOS Signals

De Ritis Ratio ($AST/ALT$):

• Viral hepatitis, NAFLD: Usually < 1
• Alcoholic liver disease: Typically > 2
• Cirrhosis (non-viral): Often ≥ 1

⭐ An AST/ALT ratio > 2, especially with elevated GGT, strongly suggests alcoholic hepatitis.

Bile Flow - Plumbing Check

• Cholestatic Markers:
  • ALP (Alkaline Phosphatase): Liver (biliary epithelium), bone, placenta. Elevation > 4x ULN suggests cholestasis.
  • GGT (Gamma-Glutamyl Transferase): Liver, biliary. Sensitive for cholestasis, alcohol. 📌 GGT: Get Good Toddy (alcohol).
  • 5'-Nucleotidase (5'-NT): Specific for hepatobiliary cholestasis.
• Cholestatic Pattern:

  Enzyme	Cholestasis	Isolated ALP ↑	Isolated GGT ↑
  ALP	↑↑↑	Bone, Placenta
  GGT	↑↑↑		Alcohol, Drugs
  5'-NT	↑↑↑

• Bilirubin: Total < 1.2 mg/dL; Direct < 0.3 mg/dL.
  • Conjugation: Bilirubin + UDPGA $\xrightarrow{\text{UGT1A1}}$ Bilirubin diglucuronide.

⭐ Isolated GGT elevation can be due to enzyme induction by alcohol or drugs (e.g., phenytoin).

Synthesis Power - Liver's Factory Output

• Serum Albumin (Normal: 3.5-5.5 g/dL)
  • ↓ indicates: Chronic Liver Disease (CLD), nephrotic syndrome, malnutrition.
  • Long half-life (~20 days) → reflects chronic synthetic dysfunction.
• Prothrombin Time (PT) / INR
  • Normal PT: 11-14 seconds; Normal INR: 0.8-1.2.
  • ↑ PT/INR indicates: Liver failure (acute/chronic), Vitamin K deficiency.
  • PT prolonged by > 3-4 seconds or INR > 1.5 suggests significant dysfunction.

  ⭐ PT/INR is a sensitive indicator of acute liver synthetic dysfunction due to the short half-life of clotting factors (especially Factor VII).

Pattern Puzzles - Decoding LFTs

Interpreting LFTs involves pattern recognition.

• Hepatocellular Injury:
  • Acute Viral Hepatitis: ALT/AST ↑↑↑ (>10-15x ULN), ALT > AST.
  • Alcoholic Liver Disease: AST > ALT (ratio often >2:1), GGT ↑↑.
  • Chronic Hepatitis: Mild-moderate ↑ ALT/AST.
  • NAFLD/NASH: Mild ↑ ALT/AST, often ALT > AST.
• Cholestatic Pattern: ALP ↑↑↑, GGT ↑↑, Bilirubin ↑. Differentiate intra- vs. extrahepatic.
• Specific Clues:
  • Autoimmune Hepatitis: ANA, ASMA, ↑IgG.
  • Wilson's Disease: ↓ Ceruloplasmin, low ALP.
  • Hemochromatosis: ↑ Ferritin, ↑ Transferrin Saturation.
  • Hepatocellular Carcinoma (HCC): AFP > 400 ng/mL highly suggestive.

⭐ Markedly elevated aminotransferases (>1000 IU/L) are typical of acute viral hepatitis, ischemic hepatitis, or drug/toxin‑induced liver injury.

High‑Yield Points - ⚡ Biggest Takeaways

• ALT is more liver-specific than AST for detecting acute hepatocellular injury.
• An AST/ALT ratio > 2 is highly suggestive of alcoholic liver disease, especially with ↑ GGT.
• Markedly ↑ ALP with ↑ GGT indicates cholestasis or biliary obstruction.
• Bilirubin (total, direct, indirect) patterns help differentiate pre-hepatic, hepatic, and post-hepatic jaundice.
• ↓ Serum albumin & ↑ Prothrombin Time (PT/INR) reflect impaired liver synthetic function.
• Isolated ↑ unconjugated bilirubin often points to Gilbert's syndrome or hemolysis.