Related Subjects:
| Chronic Liver Disease
| Cirrhosis
| Alkaline Phosphatase (ALP)
| Liver Function Tests
| Ascites Assessment and Management
| Budd-Chiari Syndrome
| Autoimmune Hepatitis
| Primary Biliary Cirrhosis
| Primary Sclerosing Cholangitis
| Wilson Disease
| Hereditary Haemochromatosis
| Alpha-1 Antitrypsin (AAT) Deficiency
| Nonalcoholic Steatohepatitis (NASH)
| Spontaneous Bacterial Peritonitis
| Alcoholism and Alcoholic Liver Disease
| Liver Transplantation
NASH (Nonalcoholic Steatohepatitis) is a severe form of non-alcoholic fatty liver disease (NAFLD), identified after excluding viral, alcoholic, and other liver diseases. It has increasingly been recognized as a major cause of liver disease that was previously categorized as cryptogenic cirrhosis and carries a risk for progressing to hepatocellular carcinoma.
About NASH
- Characterized by significant fat deposits in the liver that cause inflammation and damage.
- Diagnosed primarily through liver function tests and liver biopsy in the absence of significant alcohol consumption.
Definitions
- Non-alcoholic Fatty Liver (NAFL): Presence of hepatic steatosis without inflammation.
- Non-alcoholic Steatohepatitis (NASH): Hepatic steatosis accompanied by liver inflammation.
Histology
- NAFL: Characterized by macrovesicular steatosis.
- NASH: Features steatosis, lobular inflammation, ballooning, and in severe cases, fibrosis or cirrhosis.
Incidence
- Affects 20-30% of the general population, making it the most common liver disorder worldwide.
- In the USA, up to 35% of adults have NAFLD, with 2-7% having NASH, correlating with rising obesity rates.
Associations
- Strongly associated with metabolic syndrome components like central obesity, insulin resistance, type 2 diabetes, and dyslipidemia.
- Minor associations include HIV, certain ethnicities (particularly Hispanic), sleep apnea, hypothyroidism, and PCOS.
Risks of Progression
- Increased risk with obesity (BMI > 30 kg/m2).
- Higher prevalence and faster progression in individuals over 45 with type 2 diabetes.
- An AST/ALT ratio greater than 1 is frequently observed in advanced disease.
Pathophysiology
- Described by the "two-hit hypothesis": The first hit involves lipid accumulation in hepatocytes (steatosis), which sensitizes the liver to further damage from a second hit involving additional factors (oxidative stress, lipotoxicity, cytokines) that lead to inflammation and fibrosis.
Differential Diagnoses to Exclude
- Alcoholic liver disease: Considered if alcohol intake is above a minimal threshold.
- Drug-induced liver injury from medications such as prednisone, tamoxifen, and amiodarone.
- Viral hepatitis B and C, which may coexist with NAFLD.
- Other hereditary and metabolic liver diseases like Wilson's disease and hemochromatosis.
Clinical Features
- Most patients are asymptomatic; often detected incidentally through abnormal liver tests.
- Symptoms when present may include fatigue, right upper quadrant pain, and signs of liver failure in advanced stages.
Assessment of Disease Progression
- Liver biopsy remains the gold standard for distinguishing NASH from NAFL and assessing the degree of liver fibrosis.
- Non-invasive methods like FibroScan or elastography, and blood tests for fibrosis markers (ELF test), are increasingly used to estimate liver fibrosis and cirrhosis.
Management
- Lifestyle modification remains the cornerstone of management, focusing on diet changes and physical activity to achieve weight loss.
- Pharmacotherapy may include the use of vitamin E and pioglitazone, particularly in diabetic patients.
- Advanced cases may require evaluation for liver transplantation.
References