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Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD)

  1. Simple fatty liver disease (or non-alcoholic fatty, NAFL) - benign prognosis
  2. Non-alcoholic steatohepatitis (NASH). - Associated with fibrosis and prognosis to cirrhosis.
Aetiology and pathogenesis
  1. Most individuals with NAFLD have insulin resistance but not necessarily overt glucose intolerance.
  2. The current two-hit hypothesis explains why not everyone with fatty liver disease develops hepatic fibrosis.
  3. The ‘first hit’ result in steatosis (fatty liver), which is only complicated by inflammation if a ‘second hit occurs’.
  4. Leptin is then needed to cause hepatic fibrosis.
NASH associated with:
  1. DM
  2. Obesity
  3. Dyslipidemic
  4. Increase insulin resistance)
Clinical features
  1. Most patient have Asymptomatic but have abnormal LFTs, particularly elevation of the transaminases or isolated elevation of the GGT.
  2. May presents with a complication of cirrhosis such as variceal heamorrhage or hepatocellular carcinoma.
  3. In contrast to alcoholic liver disease, NAFLD is the most likely diagnosis in a obese patient and a negative chronic liver disease screen.
M/C cause of cryptogenic cirrhosis is NASH (Ref. Hari. 18th ed., pg- 2605)
Causes of NASH
  1. Obesity
  2. DM
  3. TPN,
  4. Drug (Steroid, tamoxifen, tamoxifen, Estrogen
  5. Wilson disease, genotype – 3
  6. Hepatitis C

Extra Edge Gall stone not a cause of NASH.


Liver function tests
  1. AST, ALT raised, not more than 2 times of normal. (ALT > AST)
  2. Elevated alkaline phosphatase levels are seen in about 30% of case.
  3. It is important to differentiate simple fatty liver disease (NAFL), which does not require follow-up, from NASH.
  4. Elevated serum transaminases greater than twice the upper limit of normal and the presence of the metabolic syndrome (hypertriglyceridemia, hypertension, diabetes mellitus, an elevated BMI > 25 and especially truncal obesity are useful predictors of NASH.
Liver biopsy
Histologically, fat deposition is usually macrovesicular fat seen in acute fatty, Mallory bodies, neutrophil infiltration and pericellular fibrosis.


Extra Edge Clofibrate has no role in the treatment of NASH


Management (Ref. Hari. 18th ed., Pg- 2605)
  1. Weight loss, Reducing BMI and insulin resistance
  2. Orlistat
  3. Metformin is the first-line treatment in type 2 diabetes with NAFLD.
  4. Thiazolidinediones (pioglitazone) also improve LFTs in NAFLD
  5. Weight loss reduces serum transaminase levels, improve liver fibrosis and reduce insulin resistance.
  6. Ursodeoxycholic acid
  7. 7. Bariatric surgery
Important Points

Causes of Macrovesicular Steatosis (Ref. Hari. 18th ed., Pg - 2605)

  1. Insulin resistance, hyperinsulinemia
    1. Centripetal obesity
    2. Type 2 diabetes
  2. Medications
    1. Glucocorticoids
    2. Estrogens
    3. Tamoxifen
    4. Amiodarone
  3. Nutritional
    1. Starvation
    2. Protein deficiency (Kwashiorkor)
    3. Choline deficiency
  4. Liver disease
    1. Wilson disease
    2. Chronic hepatitis C—genotype 3
    3. Indian childhood cirrhosis
    4. Jejunoileal bypass

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