nonalcoholic%20fatty%20liver%20disease
NONALCOHOLIC FATTY LIVER DISEASE

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 and liver enzyme levels and decrease histologic features

Pharmacotherapy

  • Pharmacological therapy is indicated in patients with progressive nonalcoholic steatohepatitis (NASH) and in those in early stage of NASH with increased risk of progressing to fibrosis (age >50 years, diabetes, metabolic syndrome, increased ALT or active NASH with high necroinflammatory activity)
  • Pharmacologic treatments for nonalcoholic fatty liver (NAFL)/NASH are targeted at underlying metabolic syndrome-related diseases such as obesity, type 2 diabetes mellitus, dyslipidemia and 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 has improved all histological features (except for fibrosis) and has resolution of NASH more often than the placebo
  • There is concern on side effects of Pioglitazone such as weight gain, bone fractures in women, and rarely congestive heart failure thus long-term treatment is not advisable

Incretin Mimetics (eg Liraglutide)

  • Act on glucose-insulin interplay and 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 NASH remission without worsening fibrosis

Antioxidants, Cytoprotective and Lipid-lowering Agents

Vitamin E

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

Statins (eg Ezetimibe and HMG-CoA reductase)

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


Angiotensin II Receptor Antagonist (ARB)

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

Other Drugs

Pentoxifylline

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