356.3 🏥 內科專科考前版

356.3.1 Mechanistic Deep Dive

356.3.1.1 Pathogenesis MASLD/MASH

  • Insulin resistance
  • Free fatty acid flux to liver
  • Lipid peroxidation, oxidative stress
  • Mitochondrial dysfunction
  • Inflammasome activation
  • Adipokine signaling

356.3.1.2 Alcohol Metabolism

  • ADH → acetaldehyde → acetic acid
  • Variable enzymes (ALDH polymorphisms — Asian flush)
  • Mitochondrial AST damage
  • Steatosis via altered redox

356.3.1.3 THR-β Agonism (Resmetirom)

  • Activates β isoform in liver
  • ↓ Hepatic lipid + LDL
  • Not increasing T3 systemically
  • Liver-selective

356.3.2 Recent Trials & Updates

356.3.2.1 MAESTRO-NASH (2023) — Resmetirom

  • MASH F2-F3 fibrosis
  • 12-week + 52-week histology endpoints
  • ↑ MASH resolution + fibrosis improvement
  • FDA approval March 2024

356.3.2.2 Semaglutide for MASH

  • STEP, SUSTAIN trials
  • SYNERGY-NASH (2024)
  • ↓ MASH (positive results)

356.3.2.3 Tirzepatide for MASH

  • SURPASS series + SYNERGY-NASH
  • Even more effective than semaglutide
  • Phase 3 ongoing

356.3.2.4 Survodutide (GLP-1 / Glucagon)

  • Phase 3 for MASH
  • Promising

356.3.2.5 Retatrutide (GLP-1 / GIP / Glucagon)

  • ~ 24% weight loss
  • Phase 3

356.3.2.6 STOPAH (2015) — Pentoxifylline in AH

  • No benefit
  • Pentoxifylline no longer used
  • Corticosteroids modest benefit (~ 28-day mortality)

356.3.3 High-Yield Specialist Points

356.3.3.1 Early Liver Transplant for Severe AH

  • Mathurin 2011 (France)
  • ELITAH trial + US protocols
  • Strict psychosocial assessment
  • 30-day mortality > 50% in severe AH without transplant

356.3.3.2 Lille Score Clinical Use

  • Day 7 of steroids
  • Continue if responder (< 0.45)
  • Stop + consider transplant if non-responder (> 0.45)

356.3.3.3 Wernicke + Korsakoff in Alcoholic

  • Thiamine deficiency
  • Triad: ataxia + ophthalmoplegia + confusion
  • IV thiamine BEFORE glucose (precipitates Wernicke)

356.3.3.4 Hepatorenal Syndrome (HRS) in Cirrhosis

  • See Ch332
  • Terlipressin + albumin (FDA 2022)

356.3.3.5 Bariatric Surgery + MASH

  • Roux-en-Y > sleeve gastrectomy for MASH improvement
  • Cirrhosis not contraindication absolute
  • Compensated cirrhotic possible
  • Liver transplant + simultaneous bariatric emerging

356.3.3.6 Lean MASLD Pathophysiology

  • Visceral adiposity > BMI matters
  • Genetic predisposition (PNPLA3)
  • Same metabolic mechanism

356.3.3.7 MASLD in Children

  • Increasing
  • Earlier presentation now
  • Treatment + lifestyle similar
  • Vitamin E + lifestyle

356.3.3.8 Sleep Apnea + MASLD

  • Often coexists
  • Treatment of OSA may help MASLD
  • Screen + treat

356.3.3.9 Hereditary Iron Overload + MASLD

  • ↑ Ferritin + iron studies often elevated in MASLD
  • Distinguish from hemochromatosis
  • MRI iron + HFE genetic testing

356.3.3.10 Liver Transplant in MASLD/MASH

  • Leading indication globally (rising)
  • Recurrent steatosis common post-transplant
  • Lifestyle critical
  • Bariatric simultaneous emerging

356.3.3.11 Statins + MASLD

  • Safe even with elevated LFTs
  • Useful for CV risk reduction (top cause of mortality in MASLD)
  • Don’t avoid

356.3.4 Pearls

  • MASLD = NAFLD renamed 2023: MASH = NASH
  • ALD spectrum: steatosis → AH → cirrhosis
  • AH AST:ALT > 2, ALT rarely > 300
  • Maddrey DF > 32 severe AH: corticosteroids + Lille score day 7
  • Pentoxifylline no longer used (STOPAH 2015)
  • MASLD treatment foundation: weight loss ≥ 5-10%
  • Resmetirom (Rezdiffra) FDA 2024: first MASH drug, F2-F3 fibrosis
  • GLP-1 RA + tirzepatide: weight loss + MASH benefit
  • Pioglitazone: PPAR-γ for T2DM + MASH
  • Bariatric surgery: most effective for severe obesity