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Evaluating the Patient With Abnormal Liver Tests-1

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Title: Evaluating the Patient With Abnormal Liver Tests-1


1
Evaluating the Patient With Abnormal Liver
Tests-1
  • ????' ??? ????? ???? ????? ???? ?? ??????

2
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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.

3
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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.

4
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.
5
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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.

6
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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.

7
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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.

8
??????-1
  • 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.

9
??????-2
  • 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

10
Signs of Liver Disease and Related Conditions
11
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12
Examination
13
Obesity, increased waist circumference-NAFLD
14
Cirrhosis, Pregnancy -Spider Angiomata
15
Spider Angiomata
16
Jaundice,
17
Palmar Erythema
18
Dupuytren's contractures-Alcoholism
19
White nails, clubbing-Cirrhosis
20
Finger Clubbing
21
Parotid enlargement-Alcoholism
22
Gynecomastia, testicular atrophy-Cirrhosis
23
Caput Medusae
24
(No Transcript)
25
Itching in Primary Biliary Cirrhosis
26
Xanthomata, xanthelasma-Primary biliary cirrhosis
27
Kayser-Fleischer corneal rings -Wilson's disease
28
Signs of congestive heart failure jugular venous
distention, right pleural -effusion, S3 gallop-
Cardiac cirrhosis
29
Arterial bruit heard over the liver-
Hepatocellular carcinoma, alcoholic hepatitis,
arteriovenous malformation (rare)
30
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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.

31
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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.

32
Common Liver Tests and Associated Conditions
33
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.

34
INR-international normalized ratio
  • Impaired synthesis of vitamin K-dependent
    coagulation factors

35
Albumin
  • Cirrhosis, severe hepatocellular injury.
  • Other causes for low albumin?

36
Bilirubin
  • Any acute or chronic liver disease.
  • Congenital disorders of bilirubin metabolism.

37
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
38
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
39
Additional points -Hyperbilirubinemia
  • In acute and chronic liver diseases every point
    in the metabolism of bilirubin may be defected.

40
Abnormal Liver Test Results
  • Aminotransferases, alkaline phosphatase, and GGT
    are enzymes that are released during injury to
    liver cells or bile ducts.

41
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.

42
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.

43
Aminotransferases
  • The ratio of AST to ALT may indicate alcoholic
    liver disease when greater than 21.

44
Alkaline phosphatase
  • Cholestasis (Canalicular injury ,intrahepatic and
    extra hepatic bile duct obstruction).
  • Hepatocellular damage.
  • Children during bone growth.
  • Bone disease.
  • Pregnancy (placenta origin).

45
GGT - gamma glutamyltransferase
  • Cholestasis (Canalicular injury ,intrahepatic and
    extra hepatic bile duct obstruction).
  • Medications.
  • Ethanol

46
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.

47
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.

48
MCV
  • Alcohol consumption, folic acid and B12 deficiency

49
ADDITIONAL HEMATOLOGICAL PARAMETERS MAY BE
HELPFUL IN LIVER PATEINT EVALUATION
  • Leukopenia.
  • Thrombocytopenia .
  • These may result from hypersplenism associated
    with portal hypertension.

50
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.

51
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.

52
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) .

53
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