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Clin Lab Med Unit 1 > Liver Tests & Hepatitis Serology > Flashcards

Liver Tests & Hepatitis Serology Flashcards

1
Q

Injury to hepatocytes themselves is …

A

Hepatocellular liver disease

Examples:
Hepatitis (A,B,C)
Liver ischemia
Toxins (OTC meds, etc)

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2
Q

__________ disease refers to injury of bile ducts and/or bile flow obstruction (intra or extra-hepatic compression)

A

Cholestatic disease

Examples:
PBC and PSC (autoimmune diseases that attack the small/large bile ducts), gallstones, drug hepatotoxicity, pancreatic CA, bile duct CA

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3
Q

__________ liver disease refers to conditions in which the liver is invaded or replaced by non-hepatic substances

A

Infiltrative liver disease

Examples:
Tumor, amyloid (an abnormal protein that can be deposited in the liver), TB

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4
Q

Liver tests/chemistries that reflect hepatocellular damage

A

ALT (alanine aminotransferase)
AST (aspartame aminotransferase)

Both will be elevated in instances of hepatocellular damage

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5
Q

Liver tests that reflect cholestatic processes

A

Total bilirubin
Alkaline phosphatase (ALP)
GGT

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6
Q

Elevated alkaline phosphatase (ALP) suggests…

A

Cholestasis (bile cannot flow)

Liver, bone, intestine, placenta origin

ALP isoenzyme can be used to distinguish between liver and bone disease

5NP (5’-nucleotides) is enzyme in liver and is elevated in diseases affecting the biliary tree. 5NP can help distinguish liver as the origin

GGT when simultaneously elevated can confirm liver origin

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7
Q

Total bilirubin =

A

Sum of direct (conjugated) + indirect (unconjugated) bilirubin

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8
Q

The fraction of total bilirubin that is direct vs indirect

A

Fractionated bilirubin

Useful when standard liver tests are normal and bilirubin is elevated (ie - Hemolysis, Gilbert’s syndrome)

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9
Q

Elevated direct (conjugated) bilirubin
Elevated (or normal) indirect bilirubin
AST/ALT elevated

A

Liver disease

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10
Q

Normal direct bilirubin
Elevated indirect (unconjugated) bilirubin, making up 90% of total bilirubin
Anemia
AST/ALT normal

A

Hemolysis

Indirect bilirubin is elevated b/c too much unconjugated bilirubin is being produced by the hemolysis and the liver can’t keep up to conjugate and get rid of it all

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11
Q

Normal direct bilirubin
Elevated indirect bilirubin (>90% of total)
Normal AST/ALT
NO anemia

A

Gilbert’s syndrome

Indirect bilirubin elevated b/c can conjugate normally although normal amount is coming into the liver

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12
Q

What is gamma-glutamyl-transpeptidase?

A

GGT

Present in hepatocytes and biliary epithelial cells

Useful when:

1) ALP is elevated it confers liver specificity
2) when AST/ALT>2 it further supports Alcoholic Liver Disease

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13
Q

_____ is more specific to the liver than ______

A

ALT more specific than AST

Highest levels of ALT found in liver

ALT threshold is 29 for males, 22 for females

AST is also found in liver, skeletal and cardiac muscle, kidney, brain

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14
Q

The first step in evaluating a patient with elevated LFTs but no symptoms is to …

A

Repeat the test (fasting)

Normal liver tests do not mean the liver is normal - patients with normal ALT/AST can have significant liver disease

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15
Q

Isolated elevation of one liver test when others are normal should…

A

Raise suspicion of source other than the liver

Bilirubin - RBCs
AST - skeletal muscle, cardiac muscle, kidney, brain
ALT - skeletal muscle, cardiac muscle, kidney
LDH - Enzyme present throughout body
ALP - BONE, 1st trimester placenta, intestines

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16
Q

Herbals/vitamins known to cause drug induced liver injury

A

Ephedra
Kava
Vitamin A
Garcinia cambogia

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17
Q

Medications known to cause drug induced liver injury

A 
Acetaminophen
Statins
Antifungals/azoles
Antibiotics
Anti-TB drugs 
NSAIDs
Tegretol
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18
Q

Typical AST or ALT values in cirrhosis

A

30-90

Normal is 12-32ish

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19
Q

Typical AST or ALT values in chronic hepatitis

A

50-200

Normal 12-32

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20
Q

Typical AST or ALT values in alcoholic hepatitis

A

200-400

Normal 12-32

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21
Q

Typical AST or ALT values in acute viral hepatitis

A

300-3000 (lower for C, higher for A/B)

Normal 12-32

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22
Q

Typical AST or ALT values in Toxic of ischemic injury

A

1000-10,000

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23
Q

Mildly elevated AST/ALT suggestive of…

A

Fatty liver
EtOH related
Chronic viral hepatitis
Medication effect

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24
Q

Elevated AST suggestive of…

A

Alcoholic hepatitis
Rhabdomyolysis
Cardiac problem

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25
Q

AST:ALT ratio of ≥2 is suggestive of

A

Alcoholic Liver Disease (present in both mild and sever cases)

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26
Q

AST:ALT ratio of ≤ 2 suggestive of

A

Acute or chronic viral hepatitis
Cholestatic disease (if ALP predominates)
NASH (AST:ALT ratio usually ≤ 1)

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27
Q

Fat accumulation in the liver with NO secondary cause

A

Nonalcoholic fatty liver disease

Spectrum:
Simple steatosis (NAFL)
Non-alcoholic steatohepatitis (NASH)
Cirrhosis

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28
Q

Fatty liver without inflammation

A

Non-alcoholic fatty liver (NAFL)

Low risk of developing significant fibrosis

29
Q

Fatty liver + inflammation with hepatocytes injury +/- fibrosis

A

Non-alcoholic steatohepatitis (NASH)

Higher risk of developing significant fibrosis, cirrhosis, liver failure, and liver cancer

30
Q

Risk factors for Nonalcoholic fatty liver disease

A

Abdominal obesity
DM (insulin resistance)
HLD (high TG and low HDL)
Metabolic syndrome

31
Q

Strongest predictor for NASH

A

Metabolic syndrome

32
Q

Diagnosing NASH

A

Patient generally asymptomatic
Mildly elevated Aminotransferase (AST,ALT)
Fatty infiltration on imaging (NAFLD)
Confirmed by histology (biopsy) or Fibroscan
Liver biopsy showing steatosis, inflammation +/- fibrosis

33
Q

Management of NASH

A

Weight loss (diet, exercise, meds, surgery)
Discontinue ALL EtOH
Control DM and HLD
If progresses to cirrhosis, consider transplant
New meds in clinical trials

34
Q

Hereditary disorder of iron metabolism resulting in increased intestinal absorption of iron —> iron accumulation in skin, liver, pancreas, heart, adrenals, testes, joints, pituitary, and kidney

A

Hereditary Hemochromatosis

Autosomal recessive, most commonly due to mutations in the HFE gene

35
Q

___________ and __________ increase the risk that Hereditary Hemochromatosis will lead to fibrosis/cirrhosis

A

Excessive EtOH intake and chronic liver disease

36
Q

Hereditary Hemochromatosis can lead to what type of cancer?

A

Hepatocellular carcinoma (HCC)

Approximately 45% of all HH deaths
Associated with cirrhosis

Screening includes AFP (alpha fetoprotein, a liver cancer tumor marker) and ultrasound

37
Q

Clinical findings in Hereditary Hemochromatosis patients

A

Asymptomatic (75%)
• Screening with family Hx
• Elevation of transferrin saturation, ferritin noted
• Elevation of transaminases

Symptomatic
•Fatigue, arthralgia, loss of libido

Late
• Hepatomegaly, cirrhosis, DM, impotence, bronze pigmentation of skin, cardiomegaly +/- CHF

38
Q

Lab findings in Hereditary Hemochromatosis

A

Elevated liver tests (AST, ALT)

Screen with transferrin saturation and ferritin
• If transferrin saturation ≥ 45 AND/OR
• Ferritin >250(men)/>150(women)

If either of the above present, GI referral for HFE genotype analysis and workup

39
Q

Why is the ferritin threshold for HH lower for women?

A

We lose more blood than man through monthly menstruation

40
Q

Treatment for HH?

A

Prevent cirrhosis

Avoid Vit C, iron supplements, uncooked seafood, and EtOH

Therapeutic phlebotomy if iron overloaded

Hep A and B immunizations if not already done

Genetic screening advised for all 1st degree relatives

41
Q

Why avoid uncooked seafood if you have hereditary hemochromatosis?

A

Because the bacteria in seafood love iron and will use it up

42
Q

Autoimmune liver diseases that occur predominantly in women, at a 9:1 ratio to men

A 
Primary Biliary Cirrhosis (PBC)
Autoimmune Hepatitis (AIH)
43
Q

Autoimmune liver diseases that occur predominantly in men (5:1)

A

Primary sclerosis cholangitis (PSC)

44
Q

Immunologic attack on the intra-hepatic bile ducts that eventually leads to cirrhosis and liver failure (CHOLESTATIC liver disease)

A

Primary Biliary Cirrhosis (PBC)

AMA (anti-mitochondrial antibodies) will be POSITIVE

45
Q

Disease that is presumed to be a T-cell mediated immune attack of liver antigens

A

Autoimmune Hepatitis (AIH)

Hepatocellular infllammation, so AST/ALT predominate

46
Q

Inflammation and fibrosis of the intrahepatic and extra-hepatic bile ducts, with a strong association with IBD.

A

Primary sclerosis cholangitis (PSC)

Cholestatic liver disease

AMA is NEGATIVE

47
Q

The following test results are indicative of what disease?

AST/ALT >10 times ULN
ALP 1-3 times ULN
ASMA 90% (high titer)
AMA 10-20% (low titer)
LKMA Positive
Immunoglobulin IgG (high titer)
A

Severe autoimmune hepatitis (AIH)

48
Q

The following test results are indicative of what disease?

AST/ALT 1-3 times ULN
ALP 2-10 times ULN, +/- bilirubin elevation
ASMA 10-20% (low titer)
AMA 90-95% (high titer)
LKMA Negative
Immunoglobulin IgM (high titer)
A

Primary Biliary Cirrhosis

49
Q

Genetic disorder characterized by decreased levels of alpha-1 antitrypsin production, which normally protects against tissue injury (esp in liver and lungs)

A

Alpha-1 antitrypsin deficiency

50
Q

Alpha-1 antitrypsin deficiency in adults vs children

A

Adults are at risk for severe lung disease

Infants/children are more likely to present with liver disease

51
Q

What disease do you suspect in a non-smoker with emphysema at a young age (<45 years) or when there is a neonatal cholestasis or childhood cirrhosis?

A

Alpha-1 antitrypsin deficiency

52
Q

1 genetic liver disease in children

A

Alpha-1 antitrypsin deficiency

53
Q

Lab results indicative of alpha-1 antitrypsin deficiency

A

Mild elevation of AST/ALT
Serum alpha-1 antitrypsin decreased
Alpha-1 antitrypsin phenotype

Rule out other causes +/- liver biopsy

Tx: Liver transplant

54
Q

Rare hereditary disorder causing impaired biliary excretion and elimination of copper from the liver

A

Wilson’s Disease

Autosomal recessive defect

55
Q

When the liver’s capacity for copper is exceeded in Wilson’s patients…

A

Copper is released into the bloodstream and accumulates in the brain, cornea, joints, kidney, heart, and pancreas

56
Q

Clinical findings in Wilson’s disease

A

Usually presents between ages 5-35

Sx predominantly hepatic, neurologic, and psychiatric:
Tremor, dysarthria, incoordination, personality or behavior changes

57
Q

Pathognomonic ocular sign of Wilson’s disease

A

Kaiser-Fleisher ring

Fine pigmented granular deposits in the cornea, found in 90% of patients

Color is brownish or gray-green

Detected by naked eye, ophthalmoscope, slit lamp exam

58
Q

Dx of Wilson’s disease

A

Elevated AST/ALT
ALP usually low

Initially screen with serum ceruloplasmin (will be low in 85-90%)
<5 ug/dL is strong evidence

Ophthalmologist eval (K-F rings)

24 hour urinary copper high

+/- liver biopsy or molecular genetic testing

59
Q

Type of hepatitis spread by fecal-oral route, with epidemics associated with contaminated food and lack of sanitation

A

Acute Hepatitis A

Incubation period 15-50 days (avg 28 days)

60
Q

Lab tests indicative of Hep A

A

Significantly elevated AST/ALT >15 times normal
Elevated ALP and bilirubin

+ Anti-HAV IgM
Positive at onset of Sx and remains positive for approx 4 months

Contagious during incubation period up to 1 week after jaundice appears

61
Q

Hep A _____________ chronic

A

Never becomes chronic

99% of cases recover in 6 months

62
Q

How is Hep B transmitted?

A

Blood
Sexual contact
Parenteral contact
Perinatal transmission (Hep B + mother during delivery)

63
Q

Incubation period for Hep B

A

45-180 days

Most cases are subclinical/anicteric (70% of adults and 90% of children)

64
Q

SSx of Hep B

A

Low grade fever, anorexia, nausea, vomiting, vague abdominal pain, jaundice +/- arthralgia and rash

Elevated bilirubin, ALP
Significantly elevated ALT >15x ULN

<5% acute adults progress to chronic infection

65
Q

Hep B screening labs

A

Hep B surface antigen (HBsAg)*
(+) in active disease (chronic or acute)

Antibody to surface antigen (anti-HBs)
(+) immunity (vaccine or resolved infection)

Antibody to Hep B core antigen
(+) IgM anti-HBc (acute exposure)*
(+) IgG anti-HBc (previous exposure)
(+) Total anti-HBc (previous exposure)

*included in acute hepatits panel

66
Q

Risk factors for screening for Hep C

A 
Born 1945-1965
IVDU
Hemodialysis
ALT elevation
Clotting factor recipient prior to 1987
Transfusion/organ transplant prior to 1992
Tattoos/body piercings
Intra-nasal drug use
Recognized exposure (healthcare workers, children of (+) mother)
Incarceration
High-risk sexual behavior
HIV infection
67
Q

SSx of Hep C

A

Incubation 6-7 WEEKS
HCV asymptomatic in 70-85%

10-20% experience jaundice, fatigue, fever, nausea, vomiting, RUQ discomfort

AST/ALT usually in 100s

Bilirubin elevated

70-80% develop chronic infection (AST/ALT will be lower but close to 100 in these patients)

68
Q

For patients who have been exposed to Hep C within the last 6 months or immunocompromised, consider this test

A

HCV RNA, especially if HCV antibody non-reactive

69
Q

Other conditions that might cause AST/ALT to be >5 times the ULN

A 
Acute Hepatitis (A, B, C)
EBV
CMV
Acute Alcoholic Hepatitis
DILI
Mushroom ingestion
Acute hepatitis of pregnancy
Shock Liver (insufficient blood flow —> liver ischemia)

Clin Lab Med Unit 1 (4 decks)

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