Lab

Liver Function Test Abnormality

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Liver Function Test Abnormality, LFT Abnormality

  • Epidemiology
  1. Mild asymptomatic transaminase elevations (<5x normal) are common
    1. U.S. Prevalence may be as high as 10%
    2. However, serious liver disease is found in only 5% of these cases
  • Approach
  • Focus of evaluation
  1. Iatrogenic or Treatable disease
  2. Communicable or Inheritable disease
  3. True abnormality versus False Positive testing
  • Symptoms (mild elevations are usually asymptomatic)
  1. Constitutional Symptoms
    1. Fever
    2. Weight loss
    3. Fatigue
    4. Malaise
    5. Nausea or Vomiting
  2. Pruritus
  3. Arthralgias
  • Signs
  1. Weight loss
  2. Stigmata of Chronic Liver Disease or Cirrhosis
    1. Gynecomastia
    2. Testicular atrophy
    3. Spider nevi
    4. Finger nail Clubbing
    5. Asterixis
  3. Abdominal exam
    1. Hepatomegaly
    2. Splenomegaly
    3. Ascites
  • Differential Diagnosis (Transaminase elevation)
  1. Common hepatic causes
    1. Alcoholic Liver Disease (27%)
      1. AST/ALT ration >2
      2. GGT increased
    2. Nonalcoholic Fatty Liver Disease (25-51%)
      1. Metabolic Syndrome
      2. Increased serum Triglycerides and Serum Glucose and low HDL Cholesterol
  2. Uncommon hepatic causes
    1. Hepatitis B or Hepatitis C (18%)
    2. Hemochromatosis (3%)
      1. Serum Iron and Ferritin levels increased
    3. Hepatotoxins (medications)
  3. Rare hepatic causes
    1. Autoimmune Hepatitis (1%)
      1. More common in young women with autoimmune disorders
      2. Evaluation includes SPEP, ANA, SMA, LKM-1
    2. Alpha-1 antitrypsin deficiency (1%)
      1. Associated with premature COPD
    3. Primary biliary Cirrhosis (0.3%)
    4. Wilson Disease
      1. Consider in liver disease at a young age (e.g. <30 years old)
      2. Serum ceruplasmin abnormal
  4. Extrahepatic causes
    1. Celiac Disease
    2. Hemolysis
      1. Causes include G6PD, Sickle Cell Anemia, infection
    3. Muscular disorders (e.g. Polymyositis)
      1. Increased CPK and aldolase
    4. Hypothyroidism or Hyperthyroidism
  • Labs
  1. See Liver Function Test
  2. Markers of hepatocyte injury
    1. Precautions
      1. Liver transaminases (ALT, AST) true normal ranges are <25 IU/L in women, <33 IU/L in men
      2. For those with liver disease risk factors, the lab cut-offs (50-60 IU/L) are abnormal (not simply borderline)
      3. Transaminase elevations are considered mild if <5 times normal
      4. Elevations >5 times normal require extensive evaluation for cause
    2. Alanine transaminase (ALT)
      1. Most specific for hepatocyte injury
    3. Aspartate transaminase (AST)
      1. Less specific than ALT (present outside liver)
      2. Non-liver causes include Celiac Sprue, Hemolysis, Dermatomyositis, tissue infarction, Hyperthyroidism
    4. AST to ALT Ratio
      1. AST/ALT ratio <1 in Non-Alcoholic Fatty Liver Disease (LR+ 80, LR- 0.2)
        1. Sorbi (1999) Am J Gastroenterol 94(4): 1018-22 [PubMed]
      2. AST/ALT ratio >2 in Alcoholism (LR+ 17, LR- 0.49)
      3. AST/ALT ratio >4 in Wilson's Disease
    5. Lactate Dehydrogenase (LDH)
      1. Least specific for hepatocyte injury
      2. Dramatically increased in ischemic hepatitis
      3. Increased with alk phos in liver metastases
  3. Markers of cholestasis
    1. Serum Alkaline Phosphatase
    2. Gamma glutamyl transferase (GGT)
    3. Serum Bilirubin
  4. Marker of liver function and protein synthesis
    1. Serum Albumin
    2. Prothrombin Time
  5. Markers of advanced fibrosis
    1. Platelet Count (Thrombocytopenia)
  • Imaging
  1. Abdominal Ultrasound right upper quadrant
    1. Preferred cost-effective evaluation
  2. Abdominal CT
    1. Consider if Ultrasound is non-diagnostic
  • Management
  • Increased serum transaminases (ALT, AST)
  1. Criteria
    1. Indicated in mild, asymptomatic liver transaminase (ALT, AST) elevations <5 times normal
    2. Symptomatic or elevations >5 times normal should prompt more urgent, thorough evaluation
    3. See Alkaline Phosphatase for cholestasis causes
  2. Step 0: History and Physical
    1. Lab and diagnostic evaluation as directed by history and physical
    2. Avoid Hepatotoxins including Alcohol
    3. Consider Fasting lipid profile and Serum Glucose (or complete in step 1)
    4. Plan repeat evaluation and labs in 2-4 weeks (see Step 2)
  3. Step 1: Obtain initial lab work
    1. Hepatic panel (as above)
    2. Prothrombin Time (INR)
    3. Serum Albumin
    4. Complete Blood Count with Platelet Count
    5. Viral Hepatitis Serology
      1. Consider Hepatitis A Serology
      2. Hepatitis B Serology (HBsAg)
      3. Hepatitis C Serology
      4. Consider Monospot
    6. Serum Ferritin, Serum Iron and TIBC (Hemochromatosis)
    7. Fasting lipid profile and Fasting Glucose (or Hemoglobin A1C)
  4. Step 2: Evaluate labs, history and examination
    1. Treat specific causes
    2. Consider Non-Alcoholic Fatty Liver disease (NAFLD) - most common
  5. Step 3: General measures if no cause identified
    1. Avoid Hepatotoxins
      1. Withdraw suspected medications
      2. Abstain from Alcohol use
    2. Reduce hepatic Steatosis risks
      1. Weight loss if Overweight
      2. Improve Blood Sugar control in Diabetes Mellitus
      3. Treat Hyperlipidemia (esp. serum Triglycerides)
    3. Repeat Liver Function Tests in 2-6 months
      1. Obtain imaging as above if elevations persist
      2. Liver Function Tests often remain elevated on follow-up for longer than 2 years
      3. Lilford (2013) Health Technol Assess 17(28): 1-307 [PubMed]
  6. Step 4: Abnormal transaminases persist on recheck
    1. Obtain Ultrasound of right upper quadrant
    2. Obtain disease specific markers
      1. Complete initial labs in Step 1 if not done
      2. Ceruloplasmin (Wilson's Disease)
      3. Antinuclear Antibody
      4. Anti-Smooth Muscle Antibody
      5. Alpha-1-antitrypsin
      6. Anti-tissue transglutaminase Antibody: Celiac Sprue
    3. Consider non-hepatic transaminase elevations
      1. Peripheral Smear, Coombs test (Hemolysis)
      2. Rhabdomyolysis or Polymyositis (Creatine Kinase, aldolase)
    4. If testing as above is negative for specific cause
      1. Obese patient: See Steatosis
      2. Non-obese Patient
        1. Aminotransferases exceed twice normal
          1. Refer to Gastroenterology for biopsy
        2. Aminotransferases mildly elevated
          1. Follow serial Aminotransferases (AST, ALT)
  1. Confirm increase is due to gastrointestinal cause (e.g. as opposed to bone) with a fractionated Alkaline Phosphatase
  2. Cholestatic Liver Disease
    1. Primary Sclerosing Cholangitis
    2. Primary Biliary Cirrhosis
  3. Infiltrative Conditions
    1. Malignancy
    2. Amyloidosis
    3. Sarcoidosis
    4. Infectious disease
  4. References
    1. Loftus (2012) Mayo POIM Conference, Rochester