356.2 🩺 國考版

356.2.1 高頻考點

356.2.1.1 Nomenclature 2023

  • NAFLD → MASLD
  • NASH → MASH
  • NAFL → MAFL/MASL
  • MetALD (overlap with alcohol)

356.2.1.2 MASLD Definition

  • Hepatic steatosis > 5% + 1 cardiometabolic risk
  • BMI ≥ 25 (Asians ≥ 23), T2DM, HTN, dyslipidemia, metabolic syndrome
  • Limited alcohol use

356.2.1.3 ALD Spectrum

  • Steatosis → alcoholic hepatitis → cirrhosis
  • Heavy alcohol (women > 20 g/d, men > 30 g/d)

356.2.1.4 Alcoholic Hepatitis Features

  • AST:ALT > 2 (mitochondrial)
  • ALT rarely > 300
  • Maddrey DF > 32 = severe
  • MELD > 21 = severe
  • Neutrophilia
  • Hepatocellular ballooning + Mallory-Denk bodies on biopsy

356.2.1.5 AH Treatment

  • Alcohol cessation + nutrition + vitamins (thiamine, folate, ADEK, zinc)
  • Severe (DF > 32): corticosteroids 40 mg/d × 28 days
  • Lille score day 7: < 0.45 responder (continue); > 0.45 non-responder (stop, consider transplant)
  • STOPAH trial (2015): pentoxifylline no longer recommended

356.2.1.6 Liver Transplant for AH

  • Traditional 6 months abstinence
  • Recent: select severe AH with good psychosocial support — early transplant

356.2.1.7 MASLD Risk Factors

  • Obesity (80%+ T2DM have MASLD)
  • T2DM
  • Metabolic syndrome
  • HTN, dyslipidemia
  • PNPLA3, TM6SF2, GCKR polymorphisms

356.2.1.8 MASLD Diagnosis

  • Imaging (US, CT, MRI, FibroScan-CAP)
  • FIB-4 score for fibrosis screening
  • MR elastography most accurate
  • Biopsy for uncertain

356.2.1.9 MASLD Treatment Foundation

  • Weight loss ≥ 5-10%
  • Mediterranean diet
  • Exercise (≥ 150 min/week)
  • Limit fructose

356.2.1.10 MASH Pharmacotherapy 2024

Resmetirom (Rezdiffra) — NEW 2024 (Mar): - First FDA-approved MASH drug - THR-β agonist - For F2-F3 fibrosis non-cirrhotic - MAESTRO-NASH trial

GLP-1 RA: - Semaglutide (STEP, SUSTAIN, SYNERGY-NASH) - Liraglutide - Tirzepatide (GIP/GLP-1; SURPASS, SYNERGY)

Pioglitazone: - PPAR-γ; for T2DM + MASH - PIVENS trial

Vitamin E: - 800 IU/d non-diabetic non-cirrhotic MASH (PIVENS) - Concerns prostate cancer

Bariatric Surgery: - Most effective for severe obesity

Statins: - Safe + useful for CV risk

356.2.1.11 HCC Surveillance

  • MASH cirrhosis + ALD cirrhosis: every 6 months US ± AFP
  • Non-cirrhotic MASH: increasing recognition

356.2.1.12 Key Trials

  • STOPAH (2015): pentoxifylline no benefit in AH; corticosteroids modest
  • PIVENS (2010): pioglitazone + vit E for MASH
  • MAESTRO-NASH (2023): resmetirom positive
  • STEP, SUSTAIN, SYNERGY-NASH: semaglutide
  • SURPASS, SYNERGY-NASH: tirzepatide

356.2.2 易混淆比范

Feature ALD MASLD
Risk factor Alcohol Metabolic syndrome
AST/ALT ratio > 2 < 1 typically
Treatment Alcohol cessation + steroids severe AH Weight loss + resmetirom + GLP-1 RA
Progression Steatosis → AH → cirrhosis MAFL → MASH → cirrhosis
HCC risk Cirrhotic + non-cirrhotic Both

356.2.3 Special Topics

356.2.3.1 Maddrey Discriminant Function (DF)

  • 4.6 × (PT - control) + bilirubin

  • 32 = severe AH

  • Steroid eligibility threshold

356.2.3.2 Lille Score

  • At day 7 of steroids
  • Bilirubin, albumin, PT, age, creatinine
  • < 0.45 responder (continue steroids)

  • 0.45 non-responder (stop, transplant consideration)

356.2.3.3 Resmetirom Mechanism

  • Thyroid hormone receptor-β agonist
  • Liver-selective
  • Reduces steatosis + ALT + LDL
  • MASH-specific therapy

356.2.3.4 Lean MASLD

  • Non-obese MASLD
  • Still has metabolic risk
  • More common in Asians
  • Worse prognosis sometimes

356.2.3.5 MASH-HCC

  • Increasing recognition
  • HCC can occur even without cirrhosis
  • Cardiometabolic risk drives