354.3 🏥 內科專科考前版

354.3.1 Mechanistic Deep Dive

354.3.1.1 Bilirubin Pathway Details

  • Heme oxygenase: heme → biliverdin
  • Biliverdin reductase: biliverdin → unconjugated bilirubin
  • Albumin transport
  • OATP uptake by hepatocyte
  • UGT1A1: conjugation with glucuronic acid
  • MRP2: canalicular excretion
  • Intestinal bacteria: deconjugation → urobilinogen
  • 80% excreted as stercobilin
  • 20% reabsorbed (enterohepatic)
  • Some excreted as urobilin

354.3.1.2 Cholestasis Mechanisms

  • Impaired bile formation (intracellular)
  • Impaired transport (canalicular)
  • Bile duct destruction (PBC, PSC)
  • Extrahepatic obstruction

354.3.2 Recent Trials & Updates

354.3.2.1 Non-Invasive Fibrosis Assessment

  • Increasingly used vs liver biopsy
  • ELF + transient elastography combination
  • Multi-step algorithms (FIB-4 → FibroScan → biopsy)

354.3.2.2 MR Elastography

  • Most accurate non-invasive
  • Costly + limited availability

354.3.2.3 Vibration-Controlled Transient Elastography

  • Point-of-care
  • Increasingly available

354.3.3 High-Yield Specialist Points

354.3.3.1 Macroenzymes in LFTs

  • ↑ ALP without GGT increase: bone, placenta
  • Confirm liver origin with GGT or isoenzyme

354.3.3.2 Hereditary Hyperbilirubinemia in IBD

  • Gilbert common
  • Mistaken for hepatic disease

354.3.3.3 Pregnancy Effects on LFTs

  • ALP rises 2-4x (placenta)
  • ALT/AST slight rise
  • Albumin falls (dilutional)

354.3.3.4 Acetaminophen + Alcohol

  • Increased toxicity at lower doses
  • CYP2E1 induction
  • Glutathione depletion

354.3.3.5 Wilson Disease Workflow

  • Young + neurologic / psychiatric / liver disease
  • Low ceruloplasmin (< 20)
  • Slit-lamp for Kayser-Fleischer rings
  • 24-h urinary copper > 100
  • Liver biopsy with copper > 250 ÎŒg/g dry weight
  • Genetic testing (ATP7B)

354.3.3.6 Hemochromatosis Workflow

  • Iron overload pattern
  • Ferritin > 1000, TSAT > 45%
  • HFE genotyping (C282Y homozygous most common)
  • Liver biopsy for staging (less now with MRI)
  • Phlebotomy

354.3.3.7 Alpha-1 Antitrypsin Workup

  • Serum level
  • Phenotype (PiZZ severe)
  • COPD + liver disease
  • Augmentation therapy + liver transplant

354.3.3.8 Bile Acid Diuretic Test

  • For mild persistent cholestasis
  • Workup before biopsy

354.3.3.9 Hepatic Granulomas

  • Sarcoidosis, TB, infections, drugs, PBC
  • Biopsy + workup

354.3.3.10 Hepatic Adenoma

  • OCP-related (estrogen)
  • Bleeding + malignant transformation risk
  • Imaging + biopsy + resection if large

354.3.3.11 Focal Nodular Hyperplasia (FNH)

  • Benign
  • Central scar on imaging
  • No malignant risk

354.3.3.12 Liver Cysts

  • Simple cysts common
  • Hydatid (echinococcus)
  • Polycystic (ADPKD)

354.3.4 Pearls

  • LFT patterns: hepatocellular vs cholestatic vs mixed
  • AST/ALT ratio: alcoholic > 2; cirrhosis/muscle > 1
  • Bilirubin metabolism: heme → bilirubin → UGT → MRP2 → bile
  • Gilbert syndrome: common benign
  • Workup: pattern + history + imaging + serology + biopsy
  • Non-invasive fibrosis: FIB-4, NFS, ELF, FibroScan, MR elastography
  • Acute hepatitis (ALT > 1000): drug, viral, autoimmune, ischemic, Wilson