354.1 🎓 醫孞生版

354.1.0.1 📌 䞀頁重點

354.1.0.1.1 Liver Functions
354.1.0.1.1.1 Major Functions
  • Metabolic: glucose, lipids, amino acids, drugs
  • Synthetic: albumin, clotting factors (II, V, VII, IX, X), C, S, AT III
  • Detoxification: ammonia → urea, drug metabolism
  • Storage: vitamins (A, D, B12), iron, glycogen
  • Bile production + secretion
  • Immunologic (Kupffer cells)
354.1.0.1.2 Liver Function Tests (LFTs)

354.1.1 Hepatocellular Pattern (Injury)

  • ALT (alanine aminotransferase): more specific for liver
  • AST (aspartate aminotransferase): also in muscle, RBC
  • AST:ALT ratio:

    • 2:1 with elevated GGT: alcoholic liver disease

    • 1 (without alcohol): cirrhosis (any cause), muscle disease

    • < 1: most hepatocellular (NAFLD, viral hepatitis, autoimmune)

354.1.2 Cholestatic Pattern (Obstruction)

  • Alkaline Phosphatase (ALP): bone + liver + placenta + intestine
    • Confirm liver origin: GGT, 5’-NT, isoenzyme
  • Gamma-Glutamyl Transferase (GGT): liver-specific
  • Bilirubin (often ↑)

354.1.3 Synthetic Function

  • Albumin: half-life ~ 21 days; chronic
  • Prothrombin Time (PT/INR): clotting factors; acute (II, VII, IX, X half-life 6-100 hrs)
  • Vitamin K-dependent factors (II, VII, IX, X): vitamin K deficiency vs liver synthetic

354.1.4 Other

  • Bilirubin (total + direct):
    • Indirect (unconjugated): pre-hepatic, Gilbert
    • Direct (conjugated): hepatocellular, cholestatic
  • LDH: less specific
  • 5’-Nucleotidase: cholestasis
  • Ammonia: hepatic encephalopathy
354.1.4.0.1 Bilirubin Metabolism

354.1.5 Pathway

  1. Heme → biliverdin (heme oxygenase)
  2. Biliverdin → unconjugated bilirubin (biliverdin reductase)
  3. Transported by albumin to liver
  4. Hepatic uptake (OATP)
  5. UDP-glucuronosyltransferase (UGT1A1): conjugation
  6. Excretion into bile canaliculi (MRP2)
  7. Intestine: bacteria → urobilinogen
  8. Most reabsorbed (enterohepatic) or excreted as urobilin (urine) + stercobilin (feces)

354.1.6 Disorders of Bilirubin Metabolism

Gilbert Syndrome: - Common, benign (~ 5-10%) - UGT1A1 mutation (Asians) - Mild unconjugated hyperbilirubinemia - ↑ With fasting, stress, illness - No treatment needed

Crigler-Najjar I: - Severe UGT1A1 deficiency - Severe unconjugated hyperbilirubinemia from birth - Kernicterus risk - Phenobarbital + phototherapy - Liver transplant cure

Crigler-Najjar II: - Partial UGT1A1 deficiency - Less severe - Responds to phenobarbital

Dubin-Johnson Syndrome: - MRP2 mutation - Conjugated hyperbilirubinemia - Dark liver - Benign

Rotor Syndrome: - OATP1B1/1B3 mutations - Conjugated hyperbilirubinemia - Liver not pigmented - Benign

354.1.6.0.1 Jaundice Categories

354.1.7 Pre-Hepatic (Unconjugated)

  • Hemolysis (intravascular, extravascular)
  • Ineffective erythropoiesis
  • Resorption of hematomas
  • Gilbert syndrome
  • Crigler-Najjar I/II

Lab: - Elevated unconjugated bilirubin - Normal ALT, AST, ALP - Hemolysis markers: LDH, haptoglobin, retics, peripheral smear

354.1.8 Hepatic (Mixed)

  • Viral hepatitis
  • Alcoholic + non-alcoholic fatty liver disease
  • Autoimmune hepatitis
  • Drug-induced liver injury (DILI)
  • Hereditary (Wilson, hemochromatosis, alpha-1 antitrypsin)
  • Cirrhosis (any cause)
  • Ischemic / shock liver
  • Pregnancy-related (preeclampsia, HELLP, AFLP)

Lab: - AST/ALT elevation (hepatocellular pattern) - Bilirubin mixed - Synthetic dysfunction in severe

354.1.9 Post-Hepatic / Cholestatic (Conjugated)

Extrahepatic Obstruction: - Choledocholithiasis (gallstones in bile duct) - Pancreatic head cancer - Cholangiocarcinoma - Pancreatitis (compression) - Strictures (post-surgery, PSC) - Ampullary cancer - Mirizzi syndrome (extrinsic compression)

Intrahepatic Cholestasis: - Primary biliary cholangitis (PBC) - Primary sclerosing cholangitis (PSC) - Drug-induced cholestasis - Cholestasis of pregnancy - TPN-induced - Sepsis-related - Infiltrative (lymphoma, sarcoidosis, amyloid)

Lab: - Elevated direct bilirubin - Elevated ALP + GGT - ALT/AST less prominent - Pruritus (bile acids) - Urine dark, stool pale

354.1.9.0.1 Approach to Abnormal LFTs

354.1.10 Step 1: Pattern Recognition

  • Hepatocellular (AST/ALT >> ALP/GGT)
  • Cholestatic (ALP/GGT >> AST/ALT)
  • Mixed
  • Isolated hyperbilirubinemia

354.1.11 Step 2: Clinical Context

  • Acute vs chronic
  • Risk factors (alcohol, hepatitis exposure, medications, family history)
  • Comorbidities

354.1.12 Step 3: Imaging

  • Ultrasound abdomen first: hepatic steatosis, biliary dilatation, masses, ascites
  • CT: structural detail, malignancy
  • MRI / MRCP: biliary anatomy, lesions
  • HIDA scan: cholecystitis, biliary leak
  • ERCP: therapeutic for obstruction

354.1.13 Step 4: Serologic Workup

Viral: - HBsAg, anti-HBc, anti-HBs - Anti-HCV, HCV RNA - HAV IgM (acute) - HEV (selected) - HIV - EBV, CMV (atypical hepatitis)

Autoimmune: - ANA, ASMA, anti-LKM-1, anti-SLA, anti-LC1 (AIH) - AMA (PBC) - pANCA (PSC) - IgG4 (AIP)

Metabolic: - Ferritin + transferrin saturation (hemochromatosis) - Ceruloplasmin + urinary copper (Wilson) - Alpha-1 antitrypsin level + phenotype - Triglycerides

Other: - TSH (hypothyroidism) - Anti-tTG (celiac with mild hepatitis) - AFP (HCC)

354.1.14 Step 5: Liver Biopsy (When Needed)

  • Unclear etiology
  • Staging
  • Specific diseases (autoimmune, infiltrative)
  • Transjugular if coagulopathy or ascites

354.1.15 Step 6: Non-Invasive Fibrosis Assessment

  • FIB-4 score: age, AST, ALT, platelet
  • NAFLD Fibrosis Score (NFS)
  • ELF (Enhanced Liver Fibrosis) test
  • Transient elastography (FibroScan): shear wave
  • MR elastography: most accurate non-invasive
  • Increasingly used vs biopsy
354.1.15.0.1 Specific Patterns to Recognize

354.1.16 AST/ALT Ratio Interpretation

  • AST:ALT > 2 with GGT high: alcoholic liver disease
  • AST:ALT > 1: cirrhosis (any cause), muscle disease, ischemic hepatitis
  • AST:ALT < 1: most chronic liver diseases (NAFLD, viral, autoimmune)

354.1.17 Acute Hepatitis (ALT > 1000)

  • Drug-induced (acetaminophen)
  • Viral hepatitis (HAV, HBV, HCV acute, HEV)
  • Autoimmune hepatitis (rarely this high)
  • Ischemic (shock liver)
  • Wilson disease (acute fulminant)
  • HSV hepatitis
  • Budd-Chiari syndrome

354.1.18 Cholestatic Pattern

  • PBC: women, AMA+, pruritus
  • PSC: IBD-associated, beaded biliary
  • Drug-induced: many drugs
  • Obstruction: imaging
354.1.18.0.1 Specific Pearls

354.1.19 Acetaminophen Toxicity

  • 4 g/day in healthy; less with alcohol, malnutrition

  • N-acetylcysteine (NAC) antidote
  • King’s College Criteria for transplant
  • See Ch360 for ALF

354.1.20 Wilson Disease

  • ATP7B mutations (copper)
  • Young, neurologic, psychiatric
  • Low ceruloplasmin
  • Kayser-Fleischer rings
  • Penicillamine, trientine, zinc

354.1.21 Hemochromatosis

  • HFE mutations
  • Iron overload
  • Phlebotomy

354.1.22 Alpha-1 Antitrypsin

  • COPD + liver disease
  • Phenotype PiZZ

354.1.22.1 🩺 床邊速查

  • LFT patterns: hepatocellular (AST/ALT) vs cholestatic (ALP/GGT) vs mixed
  • AST/ALT ratio: > 2 alcohol; > 1 cirrhosis/muscle; < 1 chronic liver
  • Jaundice categories: pre-hepatic (unconjugated, hemolysis) vs hepatic (mixed) vs post-hepatic (conjugated, cholestasis)
  • Gilbert syndrome: UGT1A1, common benign
  • Workup: ultrasound first + serology + biopsy if uncertain
  • Non-invasive fibrosis: FIB-4, NFS, ELF, FibroScan, MR elastography
  • Acute hepatitis (ALT > 1000): drug, viral, autoimmune, ischemic, Wilson