Steatohepatitis, Nonalcoholic (NASH)
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- 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.
- NAFLD is the most common form of chronic liver disease in the Western world; the global prevalence is increasing.
- NAFLD prevalence in the United States is 10–35%.
- The prevalence of NASH in the United States and other Western countries has been reported as 3–5% (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.
- The incidence of NAFLD is underreported and highly variable.
Etiology and Pathophysiology
- 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 also contribute to the development and progression of NASH.
- 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.
- Medications: amiodarone, dronedarone, methotrexate, tamoxifen, valproic acid, antiretrovirals, and drugs that induce obesity (e.g., corticosteroids, antidepressants, atypical antipsychotics)
- NAFLD occurs in individuals with components of metabolic syndrome, which increases the risk of NAFLD 4- to 11-fold.
- Insulin resistance plays a central role in the pathogenesis of NAFLD and metabolic syndrome.
- Other risk factors:
- Male gender
- Hypothyroidism, hypopituitarism, sleep apnea, and polycystic ovary syndrome
- Procedures leading to rapid weight loss (small bowel resection, gastric bypass, jejunal bypass)
- Medications: corticosteroids, synthetic estrogens, amiodarone, tamoxifen, methotrexate
- Other conditions: Wilson disease, hemochromatosis, abetalipoproteinemia, galactosemia, glycogen storage diseases
- Maintain ideal weight and normal lipoprotein and serum glucose profiles.
- Avoid alcohol.
- Avoid hepatotoxic substances.
Commonly Associated Conditions
Obesity, type 2 diabetes mellitus, hypertension, hypertriglyceridemia