NONALCOHOLIC STEATOHEPATITIS (NASH)

THE DIAGNOSIS

• Longstanding NAFLD and especially NASH can result in cirrhosis and hepatocellular carcinoma
  
• NASH is nowadays the 2nd most common indication for liver transplantation in the USA
• The ongoing obesity epidemic makes NASH a serious burden of disease. There is an urgent need for effective drugs
• Gold standard for the diagnosis NASH: 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 NASH is important

Bron: The NASH education program

Biopsy, the gold standard for NASH diagnosis

Bron: The NASH education program

tHE HISTOLOGICAL PROGRESSION

• NASH 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
    

Bron: 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 NASH in 51% and 19% respectively
• For which patients? Guidelines are not conclusive. Either for all NASH patients or only for NASH 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 NAFLD 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