356.4 📋 章末速蚘 Summary

356.4.1 🔑 䞀句話瞜結

2023 nomenclature changeNAFLD → MASLD (metabolic-associated steatotic liver disease) + NASH → MASH with MetALD (overlap with alcohol use)MASLD definitionhepatic steatosis > 5% + at least one cardiometabolic risk factor (BMI ≥ 25 / Asians ≥ 23, T2DM, HTN, dyslipidemia, metabolic syndrome) + no significant alcohol useTaiwan MASLD ~ 25-30% adult prevalence (rising with obesity epidemic)ALD (alcohol-related liver disease) spectrumsteatosis (reversible) → alcoholic hepatitis (AH — AST:ALT > 2:1 classic mitochondrial AST, ALT rarely > 300, neutrophilia, Maddrey DF > 32 = severe, MELD > 21 = severe, high mortality) → alcoholic cirrhosisalcoholic hepatitis treatmentalcohol cessation foundational + nutrition (1.5 g/kg protein) + vitamins (thiamine, folate, ADEK, zinc) + severe AH (DF > 32): corticosteroids prednisolone 40 mg/d × 28 days + Lille score at day 7 (< 0.45 responder continue; > 0.45 non-responder stop + consider transplant); STOPAH trial (2015): pentoxifylline no longer recommended; early liver transplant in select severe AH with strict psychosocial assessmentMASLD spectrumMAFL (MASL — steatosis only, less progressive) → MASH (steatohepatitis with ballooning + inflammation ± fibrosis — fibrosis progression risk) → cirrhosis + HCC (even non-cirrhotic MASH); diagnosisimaging (US, CT, MR-PDFF, FibroScan-CAP) + non-invasive fibrosis scores (FIB-4 screening, NFS, ELF, transient elastography, MR elastography most accurate) + biopsy for uncertain casesMASLD/MASH management 2024(1) lifestyle foundation — weight loss ≥ 5-10% + Mediterranean diet + exercise ≥ 150 min/wk + limit fructose; (2) resmetirom (Rezdiffra) FDA approval March 2024 — first MASH drug, THR-β agonist, for non-cirrhotic MASH with F2-F3 fibrosis (MAESTRO-NASH trial); (3) GLP-1 RA (semaglutide, liraglutide) for obesity + MASH (STEP, SUSTAIN, SYNERGY-NASH); (4) tirzepatide (GIP/GLP-1) SURPASS + SYNERGY-NASH; (5) pioglitazone PPAR-γ agonist for MASH + T2DM (PIVENS); (6) vitamin E 800 IU/d non-diabetic non-cirrhotic MASH; (7) bariatric surgery most effective for severe obesity; (8) statins safe + useful for CV; SGLT2i benefitemergingsurvodutide (GLP-1/glucagon), retatrutide (GLP-1/GIP/glucagon — ~ 24% weight loss) in phase 3。

356.4.2 💊 治療粟芁

  • alcohol cessation foundational for ALD: medication (naltrexone, acamprosate, baclofen) + behavioral (CBT, AA, motivational interviewing) + multidisciplinary
  • severe alcoholic hepatitis (Maddrey DF > 32): prednisolone 40 mg/d × 28 days + Lille score day 7 (< 0.45 responder → continue, > 0.45 → stop + transplant evaluation) + aggressive nutrition (1.5 g/kg protein) + vitamins (thiamine 100 mg + ADEK + folate + zinc) + treat infections aggressively
  • mild-moderate AH: supportive + nutrition + vitamins + alcohol cessation
  • early liver transplant for severe AH: select with good psychosocial support (after first decompensation, ELITAH approach)
  • MASLD foundationweight loss ≥ 5-10% + Mediterranean diet + exercise ≥ 150 min/wk moderate + limit fructose + coffee may be protective
  • resmetirom (Rezdiffra) FDA 2024: THR-β agonist, for non-cirrhotic MASH with F2-F3 fibrosis; MAESTRO-NASH trial
  • GLP-1 RA + GIP/GLP-1: semaglutide + liraglutide + tirzepatide for obesity + MASH; weight loss + histologic improvement
  • pioglitazone: PPAR-γ for MASH + T2DM (PIVENS trial); weight gain side effect
  • vitamin E 800 IU/d for non-diabetic non-cirrhotic MASH (PIVENS); concerns prostate cancer in men
  • bariatric surgery: most effective for severe obesity + MASH; Roux-en-Y > sleeve for MASH
  • statins: safe + useful for CV risk (top cause of mortality in MASLD)
  • HCC surveillance every 6 months US ± AFP for cirrhotic + advanced MASH

356.4.3 🎯 盧醫垫的考前提醒

  1. 2023 nomenclature changeNAFLD → MASLD + NASH → MASH + MetALD (intermediate with alcohol); based on positive metabolic risk factors rather than alcohol exclusion alone
  2. MASLD epidemic in Taiwan ~ 25-30% adult prevalence: rising with obesity + T2DM epidemic; leading indication for liver transplant globally
  3. alcoholic hepatitis classic featuresAST:ALT > 2:1 (mitochondrial AST damage), ALT rarely > 300 (unlike viral/drug), neutrophilia, AST elevation moderate; biopsy shows Mallory-Denk bodies + neutrophil infiltrate + hepatocellular ballooning
  4. severity scoring AHMaddrey Discriminant Function (DF) = 4.6 × (PT - control) + bilirubin > 32 = severe; alternative MELD > 21 = severe; high 30-day mortality (15-50%)
  5. AH treatmentalcohol cessation + nutrition + vitamins + corticosteroids (prednisolone 40 mg/d × 28 days) for severe (DF > 32) + Lille score day 7 decides continuation; STOPAH (2015) ended pentoxifylline use
  6. Lille score: day 7 of steroids; < 0.45 = responder (continue 28 d); > 0.45 = non-responder (stop + consider transplant); identifies non-responders early
  7. resmetirom (Rezdiffra) FDA March 2024: first FDA-approved MASH drug; THR-β agonist liver-selective; for non-cirrhotic MASH with F2-F3 fibrosis; MAESTRO-NASH trial improved histology + fibrosis
  8. GLP-1 RA + tirzepatide + survodutide + retatrutide trials for MASH: weight loss → MASH improvement; tirzepatide and retatrutide most effective for weight loss; integrates obesity + MASLD management
  9. bariatric surgery for severe obesity + MASH: Roux-en-Y > sleeve gastrectomy for histologic improvement; compensated cirrhosis not absolute contraindication; emerging liver transplant + simultaneous bariatric
  10. lean MASLD recognition: non-obese with metabolic risk factors + steatosis + PNPLA3, TM6SF2 polymorphisms more common in Asians + worse prognosis sometimes; same metabolic mechanisms despite normal BMI