Nonalcoholic fatty liver disease is having excessive fat (in the form of triglycerides) accumulation not due to excessive alcohol consumption or other secondary causes.

It is considered as a hepatic manifestation of metabolic syndrome.

Progression of nonalcoholic fatty liver disease is variable.

Principles of Therapy

  • Essential principle of therapy of nonalcoholic fatty liver disease (NAFLD) is to treat underlying cause
  • Goal of treatment is to improve insulin resistance & liver enzyme levels & decrease histologic features


  • Pharmacological therapy is indicated in patients with progressive nonalcoholic steatohepatitis (NASH) & in those in early stage of nonalcoholic steatohepatitis with increased risk of progressing to fibrosis (age >50 years, diabetes, metabolic syndrome, increased ALT or active nonalcoholic steatohepatitis with high necroinflammatory activity)
  • Pharmacologic treatments for nonalcoholic fatty liver/nonalcoholic steatohepatitis are targeted at underlying metabolic syndrome-related diseases such as obesity, type 2 diabetes mellitus, dyslipidemia & hypertension as well as liver dysfunction itself

Insulin Sensitizers

Thiazolidinediones (eg Pioglitazone)

  • Peroxisome proliferator-activated receptor agonists with insulin-sensitizing effects
  • Recommended for patients with insulin resistance
  • It was shown in clinical trials that Pioglitazone administered over a short duration have improved all histological features (except for fibrosis) & have resolution of nonalcoholic steatohepatitis (NASH) more often than the placebo
  • There is concern on side effects of Pioglitazone such as weight gain, bone fractures in women, & rarely congestive heart failure thus long-term treatment is not advisable

Incretin mimetics (eg Liraglutide)

  • Acts on glucose-insulin interplay & have shown favorable results in pre-marketing studies on liver enzymes
  • A small pilot trial of daily injections of Liraglutide met the histological outcome of nonalcoholic steatohepatitis remission without worsening fibrosis

Antioxidants, cytoprotective & lipid lowering agents

Vitamin E

  • A free radical scavenger & a chain-breaking antioxidant in free radical reactions such as lipid peroxidation
  • Studies have shown improvement in hepatic biological & histological parameters in patients with nonalcoholic steatohepatitis
  • Further studies are needed for Vitamin E to be used in non-cirrhotic, non-diabetic nonalcoholic steatohepatitis patients

Statins (eg Ezetimibe & HMG-CoA reductase)

  • May be used in patients with nonalcoholic fatty liver disease/nonalcoholic steatohepatitis & hypercholesterolemia to prevent cardiovascular risk
  • In patients already taking statins, it is advised to continue with the medication & only consider stopping when liver enzyme levels double within 3 months of starting statins

Angiotensin II receptor antagonist (ARB)

  • Angiotensin II receptor antagonist is recommended in nonalcoholic steatohepatitis patients with hypertension
  • Inhibits fibroblast activity resulting in inhibition of tissue fibrosis in several organs

Other drugs


  • Recommended in patients with nonalcoholic steatohepatitis
  • Considered to have both antioxidant & anti-TNF alpha effects
  • Clinical trials & meta-analyses found that Pentoxifylline improved serum biochemical indices & hepatic histological change
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