Nonalcoholic Fatty Liver

Aka: Nonalcoholic Fatty Liver, Nonalcoholic Steatohepatitis, Idiopathic Fatty Liver, Steatosis, Steatohepatitis, Fatty Liver, NASH

1. See Also
   1. Acute Fatty Liver of Pregnancy
2. Epidemiology
   1. Frequent cause of mild Liver Function Test Abnormality
      1. Most common cause of abnormal ALT and AST in U.S.
      2. Affects 24% of U.S. patients
   2. Most common cause of cryptogenic Cirrhosis (U.S. adult)
   3. More common in women
3. Causes
   1. Obesity
      1. Occurs in 66% of all obese patients (BMI>30)
      2. Occurs in 90% of patients at BMI>39
   2. Hyperglycemia (75% of NASH patients)
      1. Metabolic Syndrome
      2. Type II Diabetes Mellitus
   3. Hyperlipidemia (especially Hypertriglyceridemia)
   4. Rapid weight loss
      1. Starvation
      2. Gastric Bypass
   5. Refeeding Syndrome
   6. Total Parenteral Nutrition
   7. Medications
      1. Amiodarone
      2. Diltiazem
      3. Antiretroviral Therapy (esp. Protease Inhibitors)
      4. Corticosteroids
      5. Tamoxifen
4. Symptoms
   1. Asymptomatic in most cases
   2. Fatigue
   3. Malaise
   4. Right upper quadrant pain
5. Signs
   1. Hepatomegaly (50%)
6. Differential Diagnosis
   1. Viral Hepatitis
   2. Alcoholic Hepatitis
   3. Hepatotoxins
   4. Autoimmune Hepatitis
   5. Hemochromatosis
7. Labs
   1. Liver Transaminases (ALT, AST)
      1. Normal in some cases
      2. Typically 2-3 fold increase in transaminases
         1. If over 1000 consider other cause
            1. Viral Hepatitis
            2. Hepatotoxin exposure
      3. AST/ALT ratio <1 (not true in late disease)
         1. If AST exceeds ALT, consider Alcoholic Hepatitis
   2. Alkaline Phosphatase may be increased up to 2 fold
   3. Gamma-Glutamyltransferase (GGT) increased in some cases
      1. If over 2 times normal consider Alcoholic Hepatitis
   4. Other related labs to perform
      1. Alkaline Phosphatase
      2. Serum Bilirubin
      3. Serum Albumin
      4. Prothrombin Time
      5. Viral Hepatitis Labs (HBsAg, xHCV)
8. Radiology
   1. Right upper quadrant Ultrasound (Preferred first-line)
   2. Finding: Increased liver echoes (fatty infiltrates)
      1. Does not determine disease severity
      2. Good sensitivity and Specificity
         1. Test Sensitivity: 82-89%
         2. Test Specificity: 93%
   3. CT Abdomen
      1. Better sensitivity than Ultrasound
      2. Better identification of other liver abnormalities
      3. Higher cost than Ultrasound
9. Diagnosis
   1. History, exam, lab to exclude other Hepatitis Causes
      1. See imaging and Labs above
      2. See Differential Diagnosis above
   2. Liver Biopsy (consider in complicated cases)
      1. Grades degree of fatty infiltration
      2. Fatty change
      3. Hepatocyte injury
      4. Fibrosis variably present
10. Management
    1. See Prevention of Liver Disease Progression
    2. Weight Reduction
       1. Liver Function Tests improve or normalize
       2. Fibrosis may not improve after weight loss
    3. Restrict Alcohol intake
    4. Maximize Glucose control
       1. Conditions
          1. Type II Diabetes Mellitus
          2. Metabolic Syndrome
       2. Medications: Glucophage (Metformin)
          1. Reduces transaminases, Steatosis in non-diabetics
       3. Medications: Glitazones
          1. Glitazones may be used if AST amd ALT <3x normal
          2. Monitor AST and ALT every 3 months
          3. Reduces transaminases, Steatosis in non-diabetics
    5. Lipid Reduction as needed with AntiHyperlipidemic
       1. AntiHyperlipidemic may be used if AST,ALT <3x normal
       2. Monitor AST and ALT every 3 months
       3. Statins and Lopid decrease transaminases, Steatosis
    6. Supplements that may offer benefit
       1. Betaine
       2. Vitamin E (variable efficacy)
11. Prognosis
    1. Usually benign, but risk of Cirrhosis
    2. Hepatitis occurs in 10% of patients
       1. Of the hepatitis group, a third develop Cirrhosis
12. Complications
    1. Portal Hypertension
    2. Cirrhosis if associated with severe comorbid condition
       1. Morbid Obesity (BMI >30)
       2. Type II Diabetes Mellitus
       3. AST to ALT ratio >1
    3. Cardiovascular disease results in greatest morbidity
       1. Treat underlying Hyperlipidemia
13. References
    1. Angulo (2002) N Engl J Med 346:1221-31
    2. Bayard (2006) Am Fam Physician 73:1961-68
    3. Kumar (2000) Mayo Clin Proc 75:733-9
    4. Sanyal (2002) Gastroenterology 123:1705-25