METABOLIC DYSFUNCTION-ASSOCIATED STEATOHEPATITIS (MASH)

THE DIAGNOSIS
  • Longstanding MASLD (NAFLD) and especially MASH (NASH) can result in cirrhosis and hepatocellular carcinoma
  • MASH is nowadays the 2nd most common indication for liver transplantation in the USA
  • The ongoing obesity epidemic makes MASH a serious burden of disease. There is an urgent need for effective drugs
  • Gold standard for the diagnosis MASH: liver biopsy. Biopsy also enables to establish degree of fibrosis (F1-4)
  • Less reliable:
    - Vibration-controlled Transient Elastography (VCTE) and Magnetic Resonance Elastography (MRE) can assess the degree of fibrosis
    - FIB-4 score (based on age, ASAT, ALAT, platelets) and NAFLD Fibrosis Score (NFS, adding BMI and serum albumen) predict high grade fibrosis
Why early diagnosis of MASH is important
Source: The NASH education program
Biopsy, the gold standard for MASH diagnosis
Source: The NASH education program

tHE HISTOLOGICAL PROGRESSION
  • MASH is defined according to the degree of existing fibrosis:
    • F0 no fibrosis                                                                 
    • F1 negligible fibrosis                                                     
    • F2 advanced fibrosis                                                     
    • F3 bridging fibrosis                                                        
    • F4 cirrhosis
  • Histological progression is a rather slow process: around one
    degree on the fibrosis scale per decade

the treatment; lifestyle
  • In patients who are overweight or obese:
    • 5% Weight loss leads to stabilization of fibrosis
    • 10% Weight loss leads to improvement of fibrosis
    • Two or more cups of caffeinated coffee daily: potentially useful
    • 30-60 min exercise 3-5x per week: potentially useful
    • Mediterranean diet: potentially useful
Source: The NASH education progam

the treatment; established drugs

the treatment; NEWER drugs
  • Pioglitazone 30mg and vitamin E (800 IU/D) compared to placebo: improvement in hepatocellular ballooning and/or in lobular inflammation
  • Pioglitazone 30mg compared to placebo: resolution of MASH in 51% and 19% respectively
  • For which patients? Guidelines are not conclusive. Either for all MASH patients or only for MASH stage F2 patients
  • Glucagon-like peptide-1 agonists
  • Obeticholic acid
  • Elafibranor
  • Etc.

is screening advisable?
  • Some guidelines: screen patients > 50 years with type 2 diabetes or metabolic syndrome for MASLD by liver tests and/or ultrasound
  • NICE: screen also younger but similar adults
  • AASLD: do not screen on population basis: there is no evidence for long-term benefits and cost-effectiveness