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MASH and MASLD

Shabnam Eghbali

Background

  • Metabolic dysfunction-associated steatotic liver disease (MASLD) presence of hepatic steatosis (>5% of hepatocytes with macro-vesicular steatosis) in the absence of secondary causes (e.g, EtOH or HCV GT3) and at least one of five of the below criteria:
    • BMI ≥ 25 OR waist circumference > 94 cm (M) / 80 cm (F)
    • Fasting serum glucose ≥ 100 OR 2-hr post-load glucose levels ≥ 140 OR HgbA1c ≥ 5.7% OR T2DM
    • Blood pressure ≥ 130/85 OR on anti-hypertensive medication
    • Plasma triglycerides ≥ 150 OR on lipid lowering treatment
    • Plasma HDL ≤ 40 (M) / 50 (F) OR on lipid lowering treatment
  • Metabolic dysfunction-associated steatohepatitis (MASH) evidence of active inflammation and cellular injury ± fibrosis
  • Strong association with metabolic syndrome, T2DM, HTN, obesity
  • Prevalence of MASLD is 25-30% in general population and is now the leading cause of transplantation in American women
  • MASLD is asymptomatic and frequently found incidentally via imaging
  • MASH manifests with elevated liver enzymes, typically 2-5x the ULN, in a roughly 1:1 ratio (as opposed to alcoholic steatohepatitis), though ALT may be higher than AST. MASLD or MASH does NOT cause RUQ pain. Patients can still have normal liver enzymes with MASLD or MASH.

Evaluation

  • Exclusion of alternative causes and comorbid liver conditions: HCV, HBV, EtOH, etc.
  • Screen for comorbid metabolic disorders: Lipid panel, hemoglobin a1c
    • Primary risk assessment with FIB-4 (see NITs section)
  • Diagnosis commonly made via imaging
  • US is used most frequently, although conventional B mode US lacks sensitivity for lower degrees of steatosis. As a result, controlled attenuation parameter (CAP) on VCTE (Ie FibroScan) is commonly used.
  • MRI is also acceptable. MRI-proton density fat fraction is a precise method for liver fat quantification (available for clinical care at VUMC)
    • Liver biopsy should be considered when non-invasive testing suggests significant fibrosis (≥F2)

Management

  • Aggressive risk factor modification and management of comorbidities (HLD, HTN, T2DM)
  • Weight loss: Mediterranean diet>low fat diet (dose dependent improvement), increased coffee consumption is associated with less progression of liver disease
  • MASLD (fat only) Weight Loss Goal: > 5% of body weight
  • MASH (fat and inflammation) Weight Loss Goal: >10% of body weight
    • Consider referral to weight loss clinic (BMI >40, or >35 with metabolic comorbidities)
  • Once the patient is diagnosed with MASLD, evaluation for fibrosis is indicated
    • Fibrosis-4 (FIB 4) score: First line assessment. Assesses probability of fibrosis.
    • Elastography: More accurate can be vibration based (fibroscan), US based (sheer-wave), or MR-based. Available at VUMC and can be ordered by anyone. Insurance will not cover MRE if BMI <35
      • Fibroscan: <10kPa r/o advanced chronic liver disease (fibrosis); 10-15kPa are suggestive of advanced chronic liver disease; >15kPa are highly suggestive.
  • Encourage etoh cessation; contributes to fatty liver disease progression
  • FDA recently approved Rezdiffra (resmetirom) for the treatment of adults with noncirrhotic MASLD with moderate to advanced liver scarring (fibrosis), to be used along with diet and exercise
  • SGLT2 Inhibitors: May reduce steatosis in patients with MASLD+ DM
  • Vitamin E: Can improve steatosis and inflammation in the setting of biopsy-proven MASH with evidence of hepatic fibrosis (fibrosis score 2+) in patients w/o DM
  • GLP-1 agonists: Consider for patients with MASH+DM/obesity as it confers cardiovascular benefit and improves steatosis but probably not fibrosis
  • GLP-1/GIP agonist (e.g, semaglutide) Tirzepatide): Can reduce steatosis. Can be use in patients with DM or obesity + NAFLD
  • Metformin, DPP4, statins, and silymarin are well studied in MASH and do not offer meaningful histologic benefit
  • In the pipeline: FGF21 agonists, THR beta agonists, PPAR agonists

Additional Information

  • Statins: should be used for HLD in pts with MASH, MASLD, and MASH cirrhosis

  • Statin use in decompensated MASH cirrhosis is controversial, and they are less likely to derive benefit given overall poor prognosis, discontinue w/acute on chronic liver failure.