Liver enzymes

Question 1

Bilirubin is a breakdown product of heme (ferroprotoporphyrin IX).

Answer 1

The initial steps of bilirubin metabolism occur in reticuloendothelial cells, predominantly in the spleen.

Question 2

normal values of total serum bilirubin

Answer 2

are between 1.0 and 1.5 mg/dL, with 95% of a normal population falling between 0.2 and 0.9 mg/dL.

Question 3

Normal values for the indirect component are

Answer 3

between 0.8 and 1.2 mg/dL.

Question 4

The most frequently reported upper limit

Answer 4

of normal for conjugated bilirubin is 0.3 mg/dL.

Question 5

The presence of conjunctival icterus

Answer 5

suggests a total serum bilirubin level of at least 3.0 mg/dL but does not allow differentiation between conjugated and unconjugated hyperbilirubinemia.

Tea- or cola-colored urine may indicate the presence of bilirubinuria and thus conjugated hyperbilirubinemia.

Question 6

the most sensitive markers of acute hepatocellular injury,

Answer 6

The serum aminotransferases (also called transaminases),

ALT (formerly serum glutamic pyruvic transaminase, or SGPT)
AST (formerly serum glutamic oxaloacetic transaminase, or SGOT) catalyze the transfer of the α-amino groups of alanine and l-aspartic acid, respectively, to the α-keto group of ketoglutaric acid.

Question 7

a cytosolic enzyme also found in many organs, is present in greatest concentration by far in the liver and is, therefore, a more specific indicator

Answer 7

ALT

Question 8

The differential diagnosis of marked elevations of aminotransferase levels (>1000 U/L)

Answer 8

includes viral hepatitis (A to E), toxin- induced liver injury, DILI, ischemic hepatitis, and less commonly, autoimmune hepatitis, acute Budd-Chiari syndrome, ALF caused by Wilson disease, and acute obstruction of the biliary tract.

Question 9

If the AST level is less than 300 U/L, a ratio of AST to ALT of more than 2 suggests

Answer 9

alcohol- associated liver disease, and a ratio of more than 3 is highly suggestive of alcohol-associated liver disease

ratio results from a deficiency of pyridoxal 5′-phosphate in patients with alcohol- associated liver disease;

ALT synthesis in the liver requires pyridoxal phosphate

Question 10

When a patient with chronic alcohol-associated liver disease sustains a superimposed liver injury, particularly acetaminophen hepatotoxicity,

Answer 10

the aminotransferase levels can be strikingly elevated, yet the AST/ ALT ratio is maintained.

Question 11

CHRONIC, MILD ELEVATIONS, ALT > AST (<150 U/L OR 5 × NORMAL)

Answer 11

Hepatic
α1-Antitrypsin deficiency 
Autoimmune hepatitis
Chronic viral hepatitis (B, C, and D) Hemochromatosis
Medications and toxins
Steatosis and steatohepatitis 
Wilson disease 

Nonhepatic
Celiac disease
Hyperthyroidism

Question 12

SEVERE, ACUTE ELEVATIONS, ALT > AST (>1000 U/L OR > 20-25 × NORMAL)

Answer 12

Hepatic
Acute bile duct obstruction
Acute Budd-Chiari syndrome Acute viral hepatitis Autoimmune hepatitis
Drugs and toxins
Hepatic artery ligation Ischemic hepatitis Wilson disease

Question 13

SEVERE, ACUTE ELEVATIONS, AST > ALT (>1000 U/L OR >20-25 × NORMAL)

Answer 13

Hepatic
Medications or toxins in a patient with underlying alcohol-associated liver injury

Nonhepatic
Acute rhabdomyolysis

Question 14

Chronic, mild elevations, AST > ALT (<150 U/L, <5 × normal)

Answer 14

Hepatic
Alcohol-associated liver injury (AST/ALT >2:1, AST nearly always <300 U/L)
Cirrhosis

Nonhepatic
Hypothyroidism
Macro-AST Myopathy Strenuous exercise

Question 15

The first step in the evaluation of mildly elevated serum aminotransferase levels

Answer 15

is to repeat the test to confirm persistence of the elevated value.

Question 16

The clinical onset of Wilson disease

Answer 16

is usually between 3 and 55 years of age; the diagnosis should be considered initially in all patients age 40 or younger and those older than age 40 with aminotransferase elevations that remain unexplained after other causes are excluded

Question 17

has a serum half-life of approximately 7 days, and although the sites of degradation are unknown,

Answer 17

ALP

clearance of ALP from serum is independent of either patency of the biliary tract or functional capacity of the liver

Question 18

In a person with isolated elevation of the serum ALP level,

Answer 18

the serum GGTP or 5′NT is used to distinguish a liver from a bone origin of the ALP elevation

Question 19

elevated serum GGTP level

Answer 19

has high sensitivity for hepatobiliary disease, its lack of specificity limits its clinical utility

Question 20

GGTP is elevated in patients

Answer 20

taking antiepileptics, including phenytoin, carbamazepine, valproic acid, and barbiturates, as well as some drugs used in antiretroviral therapy, such as non-nucleoside reverse transcriptase inhibitors and the protease inhibitor abacavir.

Question 21

PBC is a classic autoimmune disease.

Answer 21

immunologic injury is characterized by T cell–mediated destruction of the intrahepatic bile ducts.
Although predominantly a disease of middle- aged women, with a median age at diagnosis of approximately 50 years, 5% to 10% of affected patients are men.

Question 22

Albumin

Answer 22

The average adult pro- duces approximately 15 g/day and has 300 to 500 g of albumin distributed in body fluids.

The liver has the ability to double the rate of synthesis in the setting of rapid albumin loss or a dilutional decrease in the serum albumin concentration

half-life of albumin is 14 to 21 days; there are multiple sites of degradation, including skin, muscle, liver, and kidney, as well as leakage in the gut.

Question 23

Bland cholestasis

Answer 23

Anabolic steroids

Estrogens

Question 24

Cholestatic hepatitis

Answer 24

Angiotensin-converting enzyme inhibitors: captopril, enalapril Antimicrobials: amoxicillin-clavulanic acid, ketoconazole Azathioprine
Chlorpromazine
NSAIDs: sulindac, piroxicam

Question 25

Granulomatous hepatitis

Answer 25

Allopurinol
Antibiotics: sulfonamides
Antiepileptics: carbamazepine, phenytoin
Cardiovascular agents: hydralazine, procainamide, quinidine Phenylbutazone

Question 26

Vanishing bile duct syndrome

Answer 26

Amoxicillin-clavulanic acid
Chlorpromazine
Dicloxacillin
Flucloxacillin
Macrolides

Question 27

Extrahepatic Causes of Cholestatic Liver Enzymes in Adults

INTRINSIC

Answer 27

AIDS cholangiopathy Ampullary cancer Ascariasis
Autoimmune pancreatitis Cholangiocarcinoma Choledocholithiasis CMV
Cryptosporidiosis Immune-mediated duct injury Infections
Malignancy
Microsporidiosis Parasitic infections PSC

Question 28

EXTRINSIC

Answer 28

Gallbladder cancer
Malignancy
Metastases, including portal adenopathy from metastases Mirizzi syndrome
Pancreatic cancer
Pancreatic pseudocyst
Pancreatitis

Question 29

Serum albumin levels less than 3 g/dL in a patient with newly diagnosed hepatitis

Answer 29

should raise suspicion of a chronic process.

Serum albumin is an excellent marker of hepatic synthetic function in patients with chronic liver disease and cirrhosis

Question 30

___ is the end result of a complex series of enzymatic reactions involving clotting factors, all of which are produced in the liver except factor VIII, which is produced by vascular endothelial cells

Answer 30

Clotting

Question 31

Factors involved in the synthesis of prothrombin

Answer 31

include II, V, VII, and X.

Question 32

used to express the degree of anticoagulation on warfarin therapy.

Answer 32

The INR

Question 33

A prolonged prothrombin time can be caused by a number of conditions besides reduced hepatic synthetic function:

Answer 33

congenital deficiency of clotting factors, vitamin K deficiency (vitamin K is required for normal functioning of factors II, VII, IX, and X), and DIC.

Question 34

can be identified by measuring a factor VIII level in serum;

Answer 34

DIC

the level is decreased in DIC and normal or increased in liver disease.

Question 35

allows an assessment of current hepatic synthetic function;

factor VII has the shortest serum half-life (6 hours) of all the clotting factors.

Answer 35

The prothrombin time

Question 36

Used to allocate donor organs for LT

Answer 36

The INR, along with total serum bilirubin and creatinine levels, are components of the MELD score

Question 37

is not an accurate measure of bleeding risk in patients with cirrhosis, because it assesses only the activity of procoagulant clotting factors, not anticoagulant factors such as protein C and antithrombin, the production of which is also reduced in cirrhosis.

Answer 37

The prothrombin time

Question 38

a glucosaminoglycan produced in mesenchymal cells and widely distributed in the extracellular space.

Answer 38

Hyaluronic acid

A fasting hyaluronic acid level greater than 100 mg/L had a sensitivity of 83% and specificity of 78% for the detection of cirrhosis in patients with a variety of chronic liver diseases

Question 39

Indocyanine Green Clearance

Answer 39

Indocyanine green (ICG) is a nontoxic dye that is cleared exclusively by the liver; 97% of an administered dose (0.5 mg/kg given
as an IV bolus) is excreted unchanged into bile. 

can be measured directly by spectrophotometry.

Question 40

Possible uses of ICG

Answer 40

include the assessment
of hepatic dysfunction, measurement of hepatic blood flow, and
prediction of clinical outcomes in patients with liver disease.

Question 41

has been studied as a

measure of functional hepatic mass.

Answer 41

Galactose Elimination Capacity

given as a single IV bolus (0.5 g/kg)

Question 42

Caffeine clearance tests

Answer 42

quantify functional hepatic capacity by assessing the activity of cytochrome P450 1A2, N-acetyltransferase,and xanthine oxidase

given orally (200 to 366 mg), and
levels are measured in blood, urine, saliva, breath, or scalp hair.

Question 43

Lidocaine Metabolite Formation

Answer 43

Lidocaine is metabolized to its major metabolite monoethyl-glycinexylidide (MEGX) by the hepatic cytochrome P450 sys-
tem.

Question 44

BILE ACIDS

Answer 44

synthesized from cholesterol in hepatocytes, conjugated to glycine or taurine, and secreted into bile

Question 45

are sensitive but nonspecific indicators of hepatic
dysfunction and allow some quantification of functional hepatic
reserve.

Answer 45

Serum bile acids

Question 46

Acetaminophen Toxicity

Answer 46

The dose of acetaminophen exceeds 15 g, almost 4 times the recommended daily dose, in 80% of cases.

Acetaminophen doses within the therapeutic range (≤4 g/day) can be sufficient to cause liver injury in susceptible persons, such as those who use ethanol chronically.

Question 47

The King’s College criteria

Answer 47

identify patients with a poor prognosis from acetaminophen-induced liver injury:
those with an arterial pH below 7.3 or those with an INR above 6.5
serum creatinine level above 3.4 g/dL
stage 3 to 4 hepatic encephalopathy

Question 48

The score has subsequently been validated as an accurate predictor of survival in patients with advanced liver disease.

Answer 48

The MELD score incorporates 3 objective variables into a mathematical formula: 9.57 × loge(creatinine) + 3.78 × loge(total bilirubin) + 11.2 × loge(INR) + 6.43.

The working range is 6 to 40, and the score has been shown to correlate with mortality in patients undergoing surgery other than LT, including hepatic resection, other abdominal procedures, and cardiac surgery