Evaluating the Patient With Abnormal Liver Tests-1

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Evaluating the Patient With Abnormal Liver
Tests-1

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• A 20 years old women with severe hepatitisan
  aspartate (AST ,GOT)or alanine aminotransferase
  (ALT ,GPT) levels of gtx 10ULN.
• A 42-year-old asymptomatic man with AST or GPT
  levels of x 2-5ULN.
• A 35-year-old woman with itching and an alkaline
  phosphatase level of x 2-4ULN.
• A obese woman with right-upper-quadrant pain and
  minimal aminotransferase elevation.

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• Abnormal liver test results are a common problem
  in clinical practice.
• Patients with abnormal liver tests pose clinical
  challenges in diagnosis.
• Aminotransferase elevation occurs in
  approximately 8 of Americans, with men (9.3)
  more likely to have abnormalities than women
  (6.6).
• Not all who have abnormal liver test results will
  be found to significant acute or chronic liver
  diseases.

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Upper Limit of Normal ALT Levels

• Updated upper limits
• Males 30 U/L (-25 from previous ULN)
• Females 19 U/L (-37 from previous ULN)
• Based on retrospective cohort study
• 6835 first time blood donors 1995-1999
• Anti-HCV negative and no contraindication to
  donation
• ALT activity independently related to
• BMI
• Abnormal lipid or carbohydrate metabolism

Keeffe EB, et al. Clin Gastroenterol Hepatol.
200861315-1341. Prati D, et al. Ann Intern Med.
20021371-9.
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• Men are also more likely to have underlying
  chronic liver disease, including
• Nonalcoholic fatty liver disease
  (NAFLD).
• Hepatitis B.
• Hepatitis C with or without alcoholic
  liver disease.
• Alcoholic liver disease.
• NAFLD is often the most likely diagnosis when
  abnormal liver tests are encountered in adults in
  the absence of overt signs of advanced liver
  disease.

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• The presence of elevated aminotransferase and
  gamma glutamyltranspeptidase (GGT) serum levels
  can indicate a greater likelihood of finding a
  cause for the liver injury.
• Additional factors that may cause abnormal liver
  tests in adults in the absence of overt signs of
  advanced liver disease are
• Ethanol.
• Medications.

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• If there are no physical signs of chronic liver
  disease in patients with mild increases of
  aminotransferase or alkaline phosphatase, it may
  be best to simply retest the patient in 3-5
  months.
• If more than 1 liver test result is abnormal or
  test values are moderately or markedly elevated,
  the patient should be evaluated immediately.
• A careful history and physical examination
  coupled with a thoughtful laboratory and
  radiologic evaluation will often provide a likely
  diagnosis.

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• The symptoms of liver disease are nonspecific.
• Anorexia, nausea and vomiting, fever and chills,
  right-upper-quadrant pain, dark urine and
  light-colored stools, or alteration of taste for
  cigarettes (suggesting acute hepatitis) may be
  present.
• Dry mouth and dry eyes are associated with
  autoimmune disorders such as primary biliary
  cirrhosis.
• Pruritus develops with intrahepatic cholestasis
  or extrahepatic biliary blockage.

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• In advanced liver disease, symptoms of confusion
  and disorientation may indicate hepatic
  encephalopathy.
• A history of illicit or prescribed medications,
  ethanol use, tattoos (especially
  self-administered), multiple sexual partners, and
  travel to endemic areas can raise questions of
  drug-induced or chronic viral hepatitis.
• The presence of type 2 diabetes mellitus,
  hypertension, or hyperlipidemia can suggest NAFLD

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Signs of Liver Disease and Related Conditions
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Examination
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Obesity, increased waist circumference-NAFLD
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Cirrhosis, Pregnancy -Spider Angiomata
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Spider Angiomata
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Jaundice,
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Palmar Erythema
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Dupuytren's contractures-Alcoholism
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White nails, clubbing-Cirrhosis
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Finger Clubbing
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Parotid enlargement-Alcoholism
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Gynecomastia, testicular atrophy-Cirrhosis
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Caput Medusae
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Itching in Primary Biliary Cirrhosis
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Xanthomata, xanthelasma-Primary biliary cirrhosis
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Kayser-Fleischer corneal rings -Wilson's disease
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Signs of congestive heart failure jugular venous
distention, right pleural -effusion, S3 gallop-
Cardiac cirrhosis
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Arterial bruit heard over the liver-
Hepatocellular carcinoma, alcoholic hepatitis,
arteriovenous malformation (rare)
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• Chronic liver disorders tend to group within
  specific age ranges.
• In the teenage years, Wilson's disease and
  autoimmune hepatitis are the most prevalent
  chronic liver diseases.
• During the twenties, Wilson's disease continues
  to present as liver disease up to the age of 25
  years, and autoimmune hepatitis and chronic viral
  hepatitis also occur.
• In the 30-year age group, chronic viral hepatitis
  and primary biliary cirrhosis (90 are women) are
  likely.

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• During the forties and fifties, primary biliary
  cirrhosis remains prevalent in women and
  alcoholic hepatitis, chronic viral hepatitis
  occur in men.
• Drug-induced liver disease can be found at any
  age, although it is more common in older adults.
• Primary sclerosing cholangitis may also occur at
  any age, although it tends to occur in men in
  their twenties and thirties.
• NAFLD coupled with metabolic syndrome occurs at
  any age.

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Common Liver Tests and Associated Conditions
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Abnormal Liver Test Results-1

• Most laboratory liver tests are not actual tests
  of liver function, although hepatic function can
  be inferred from
• Prothrombin times (international normalized
  ratio).
• Albumin levels.
• Bilirubin levels.

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INR-international normalized ratio

• Impaired synthesis of vitamin K-dependent
  coagulation factors

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Albumin

• Cirrhosis, severe hepatocellular injury.
• Other causes for low albumin?

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Bilirubin

• Any acute or chronic liver disease.
• Congenital disorders of bilirubin metabolism.

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Causes for Hyperbilirubinemia

1. Increased bilirubin production
2. Reduced bilirubin uptake by hepatic cells
3. Disrupted intracellular conjugation
4. Disrupted secretion of bilirubin into bile
   canaliculi
5. Intra/extra-hepatic bile duct obstruction

Lead to increase in free (unconj.)
bilirubin Result in rise in conj. bilirubin
levels
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DISRUPTED INTRACELLULAR CONJUGATION (unconj.
Hyperbilirubinemia)

• Gilberts Syndrome glucuronosyl
  transferase activity reduced to 10-30 of
  normal also accompanied by defective
  bilirubin uptake mechanism

Plasma
Bile
Hepatic cell
Alb
B
MRP2
CB
B
UDPGA
UGT1A1
Alb
sER
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Additional points -Hyperbilirubinemia

• In acute and chronic liver diseases every point
  in the metabolism of bilirubin may be defected.

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Abnormal Liver Test Results

• Aminotransferases, alkaline phosphatase, and GGT
  are enzymes that are released during injury to
  liver cells or bile ducts.

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Aminotransferases (AST, ALT)

• Hepatocellular injury Acute or Chronic
• Ethanol.
• Drug-induced hepatitis.
• Hepatitis A or B or C.
• Ischemic injury.
• Chronic liver disease.
• NAFLD.
• Acute biliary obstruction.
• Hyperthyroidism (rarely ).
• Celiac disease.
• skeletal muscle disease.

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Aminotransferases-Height of enzymes

• Marked elevations of aminotransferases occur from
  viral infection, ischemic liver injury, and
  drug-induced liver disease.
• Moderate elevations occur in patients with
  autoimmune hepatitis and some patients with
  cirrhosis.
• Minimal elevations of aminotransferases are more
  frequent in NAFLD, chronic viral hepatitis,
  alcoholism, nonspecific viral injury, and
  cholestatic liver disease.

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Aminotransferases

• The ratio of AST to ALT may indicate alcoholic
  liver disease when greater than 21.

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Alkaline phosphatase

• Cholestasis (Canalicular injury ,intrahepatic and
  extra hepatic bile duct obstruction).
• Hepatocellular damage.
• Children during bone growth.
• Bone disease.
• Pregnancy (placenta origin).

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GGT - gamma glutamyltransferase

• Cholestasis (Canalicular injury ,intrahepatic and
  extra hepatic bile duct obstruction).
• Medications.
• Ethanol

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Abnormal Liver Test Results-1

• Liver tests can be used to
• Screen for liver disease.
• Confirm suspected liver disease.
• Assist in differential diagnosis of liver
  disease.
• Monitor the progression of liver disease.
• Monitor the progress of specific
  therapies.

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Lactate dehydrogenase

• Lactate dehydrogenase (LDH) is not a reliable
  liver test but can be significantly elevated
  during
• Ischemic injury.
• Liver disease associated with hemolysis.
• Solid tumors or rapidly growing lymphomas.

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MCV

• Alcohol consumption, folic acid and B12 deficiency

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ADDITIONAL HEMATOLOGICAL PARAMETERS MAY BE
HELPFUL IN LIVER PATEINT EVALUATION

• Leukopenia.
• Thrombocytopenia .
• These may result from hypersplenism associated
  with portal hypertension.

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Cholestasis

• Laboratory tests for cholestasis include GGT and
  alkaline phosphatase.
• These enzymes are elevated in hepatobiliary
  diseases, including abnormalities of either the
  canaliculus or the intrahepatic and extrahepatic
  bile ducts and in replacement disease from
  hepatic tumors or granulomas.
• Hepatobiliary diseases include
• partial biliary tract obstruction from stones.
• pancreatitis.
• parasitic disease.
• acute cholecystitis.
• papillary dysfunction.
• With biliary disorders, the tests may fluctuate
  in value, suggesting intermittent or partial
  blockage.

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Cholestasis- additional points1

• Acute biliary tract obstruction from stones can
  be associated with aminotransferase levels gt 500
  U/L with normal or mildly elevated alkaline
  phosphatase levels.
• Medications such as ethanol, phenytoin, anabolic
  steroids, and major tranquilizers can also
  increase GGT and alkaline phosphatase levels due
  to hepatocellular enzyme induction or canalicular
  injury and cholestasis.
• Other considerations include primary biliary
  cirrhosis, sclerosing cholangitis, alcoholic
  liver disease, ductopenic syndromes.
• GGT may also be elevated in patients with NAFLD
  with obesity and diabetes mellitus.

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additional points 2-Cholestasis

• Isolated GGT elevations occur, and if other liver
  test results are normal and no ethanol or
  medication use is evident, additional workup can
  generally be delayed.
• Isolated alkaline phosphatase elevation occurs
  from bone disease, bone growth in children, and
  the placenta during pregnancy. GGT levels should
  be normal in these conditions.
• Additional evaluation of patients suspected of
  having cholestasis should include a
• Careful history and physical examination.
• Ultrasonography of the biliary tree.
• Magnetic resonance cholangiography(MRCP).
• Eendoscopic retrograde cholangiography(ERCP).
• Liver biopsy(when needed) .

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