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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
AST:ALT ratio of ≥2 is suggestive of
Alcoholic Liver Disease (present in both mild and sever cases)
26
AST:ALT ratio of ≤ 2 suggestive of
Acute or chronic viral hepatitis Cholestatic disease (if ALP predominates) NASH (AST:ALT ratio usually ≤ 1)
27
Fat accumulation in the liver with NO secondary cause
Nonalcoholic fatty liver disease Spectrum: Simple steatosis (NAFL) Non-alcoholic steatohepatitis (NASH) Cirrhosis
28
Fatty liver without inflammation
Non-alcoholic fatty liver (NAFL) Low risk of developing significant fibrosis
29
Fatty liver + inflammation with hepatocytes injury +/- fibrosis
Non-alcoholic steatohepatitis (NASH) Higher risk of developing significant fibrosis, cirrhosis, liver failure, and liver cancer
30
Risk factors for Nonalcoholic fatty liver disease
Abdominal obesity DM (insulin resistance) HLD (high TG and low HDL) Metabolic syndrome
31
Strongest predictor for NASH
Metabolic syndrome
32
Diagnosing NASH
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
Management of NASH
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
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
Hereditary Hemochromatosis Autosomal recessive, most commonly due to mutations in the HFE gene
35
___________ and __________ increase the risk that Hereditary Hemochromatosis will lead to fibrosis/cirrhosis
Excessive EtOH intake and chronic liver disease
36
Hereditary Hemochromatosis can lead to what type of cancer?
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
Clinical findings in Hereditary Hemochromatosis patients
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
Lab findings in Hereditary Hemochromatosis
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
Why is the ferritin threshold for HH lower for women?
We lose more blood than man through monthly menstruation
40
Treatment for HH?
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
Why avoid uncooked seafood if you have hereditary hemochromatosis?
Because the bacteria in seafood love iron and will use it up
42
Autoimmune liver diseases that occur predominantly in women, at a 9:1 ratio to men
``` Primary Biliary Cirrhosis (PBC) Autoimmune Hepatitis (AIH) ```
43
Autoimmune liver diseases that occur predominantly in men (5:1)
Primary sclerosis cholangitis (PSC)
44
Immunologic attack on the intra-hepatic bile ducts that eventually leads to cirrhosis and liver failure (CHOLESTATIC liver disease)
Primary Biliary Cirrhosis (PBC) AMA (anti-mitochondrial antibodies) will be POSITIVE
45
Disease that is presumed to be a T-cell mediated immune attack of liver antigens
Autoimmune Hepatitis (AIH) Hepatocellular infllammation, so AST/ALT predominate
46
Inflammation and fibrosis of the intrahepatic and extra-hepatic bile ducts, with a strong association with IBD.
Primary sclerosis cholangitis (PSC) Cholestatic liver disease AMA is NEGATIVE
47
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) ```
Severe autoimmune hepatitis (AIH)
48
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) ```
Primary Biliary Cirrhosis
49
Genetic disorder characterized by decreased levels of alpha-1 antitrypsin production, which normally protects against tissue injury (esp in liver and lungs)
Alpha-1 antitrypsin deficiency
50
Alpha-1 antitrypsin deficiency in adults vs children
Adults are at risk for severe lung disease Infants/children are more likely to present with liver disease
51
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?
Alpha-1 antitrypsin deficiency
52
#1 genetic liver disease in children
Alpha-1 antitrypsin deficiency
53
Lab results indicative of alpha-1 antitrypsin deficiency
Mild elevation of AST/ALT Serum alpha-1 antitrypsin decreased Alpha-1 antitrypsin phenotype Rule out other causes +/- liver biopsy Tx: Liver transplant
54
Rare hereditary disorder causing impaired biliary excretion and elimination of copper from the liver
Wilson’s Disease Autosomal recessive defect
55
When the liver’s capacity for copper is exceeded in Wilson’s patients...
Copper is released into the bloodstream and accumulates in the brain, cornea, joints, kidney, heart, and pancreas
56
Clinical findings in Wilson’s disease
Usually presents between ages 5-35 Sx predominantly hepatic, neurologic, and psychiatric: Tremor, dysarthria, incoordination, personality or behavior changes
57
Pathognomonic ocular sign of Wilson’s disease
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
Dx of Wilson’s disease
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
Type of hepatitis spread by fecal-oral route, with epidemics associated with contaminated food and lack of sanitation
Acute Hepatitis A Incubation period 15-50 days (avg 28 days)
60
Lab tests indicative of Hep 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
Hep A _____________ chronic
Never becomes chronic 99% of cases recover in 6 months
62
How is Hep B transmitted?
Blood Sexual contact Parenteral contact Perinatal transmission (Hep B + mother during delivery)
63
Incubation period for Hep B
45-180 days Most cases are subclinical/anicteric (70% of adults and 90% of children)
64
SSx of Hep B
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
Hep B screening labs
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
Risk factors for screening for Hep C
``` 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
SSx of Hep C
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
For patients who have been exposed to Hep C within the last 6 months or immunocompromised, consider this test
HCV RNA, especially if HCV antibody non-reactive
69
Other conditions that might cause AST/ALT to be >5 times the ULN
``` 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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