Steatohepatitis, Nonalcoholic (NASH)

Basics

Description

  • A chronic liver disease causing hepatocellular injury and inflammation due to accumulation of fat
  • Nonalcoholic steatohepatitis (NASH) is part of the spectrum of nonalcoholic fatty liver disease (NAFLD), which is defined as hepatic steatosis (on imaging or histology) without secondary causes for fat accumulation (excessive alcohol consumption, use of medications that may induce steatosis, or hereditary disorders).
  • Unlike NAFLD with simple steatosis, NASH is potentially progressive and may result in cirrhosis, liver failure, and (rarely) hepatocellular cancer.

Epidemiology

  • Since NASH was first identified in 1980, it has been increasingly recognized.
  • NAFLD is the most common liver disease in the United States.
  • NAFLD prevalence in the United States is 10–35%.
  • The prevalence of NASH in the general population ranges between 1.5% and 6.45% (1).
  • The prevalence of NAFLD increases with age.
  • Age-adjusted prevalence of NAFLD is highest in Mexican Americans, followed by non-Hispanic whites, and is lowest in non-Hispanic blacks.
  • There is little data regarding the incidence of NAFLD in the general population.

Etiology and Pathophysiology

  • The pathogenetic processes of NAFLD and its progression are multifactorial—influenced by environmental and genetic factors.
  • NAFLD is the hepatic manifestation of metabolic syndrome.
  • Insulin resistance leads to decreased inhibition of lipolysis and increased de novo lipogenesis. Free fatty acids are inappropriately shifted to nonadipose tissues, including the liver.
  • Apoptosis and oxidative stress contribute to the development and progression of NASH.
  • Hepatic mitochondrial dysfunction is central to the pathogenesis of NAFLD.
  • Two-hit hypothesis: Although NAFLD and NASH can remain stable for years, a second hepatic insult (e.g., cytokine-mediated inflammation, lipid peroxidation, or apoptosis) may trigger progression to cirrhosis.

Risk Factors

  • NAFLD occurs in individuals with components of metabolic syndrome, which increases the risk of NAFLD 4- to 11-fold.
  • Obesity is the most common risk factor for NAFLD (1).
  • NAFLD is commonly associated with type 2 diabetes, dyslipidemia, and polycystic ovarian syndrome.
  • Both the prevalence of NAFLD and stage of liver disease increase with age.
  • Other risk factors:
    • Male gender
    • Hypothyroidism, hypopituitarism, sleep apnea, hypogonadism, and psoriasis
    • Procedures leading to rapid weight loss (small bowel resection, gastric bypass, jejunal bypass)

General Prevention

  • Maintain ideal weight and normal lipoprotein and serum glucose profiles.
  • Avoid alcohol.
  • Avoid hepatotoxic substances.

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