Liver Function Test (by StatPearls | P) Flashcards
What is the characteristic of liver?
It is located in the right upper quadrant of the body and below the diaphragm
What are the functions of the liver?
1) Primary detoxification of various metabolites
2) It fxns in synthesizing proteins
3) It fxns in producing digestive enzymes
4) It has a significant role in metabolism
5) It has a fxn in terms of regulation of RBCs
6) It fxns in glucose synthesis
7) It fxns in for storage
What are the LFTs present (in this topic)?
1) Alanine transaminase (ALT)
2) Aspartate transaminase (AST)
3) Alkaline phosphatase (ALP)
4) Gamma-glutamyl transferase (GGT)
5) Serum bili
6) Prothrombin Time (PT)
7) International normalized ratio (INR)
8) Albumin
What are the functions of liver function tests (LFTs)?
1) These tests can be helpful in determining the area of hepatic injury
2) These tests can be helpful in determining the pattern of elevation
3) These tests can help organize a differential dx
True or False
The term “liver function tests” is a misnomer
True, because many of the tests do not comment on the fxn of the liver but rather pinpoint the source of the damage
Elevations in ALT and AST in out of proportion to ALP and bili denotes what?
Hepatocellular disease
Elevations in ALP and bili in disproportion to ALT and AST denote what?
Cholestatic pattern
The actual fxn of the liver can be graded based on what?
Based on its ability to produce:
1) Albumin
2) Vitamin K dependent clotting factors
At what percentage of the general population are elevated LFTs found?
Elevated LFTs are found in approx 8%
What are the characteristics of the elevation in LFTs that are found in 8% of the general population?
These elevations may be transient in pts w/out symptoms w/ up to 30% elevations resolving after 3 wks
Due to the characteristics of elevations in LFTs (that are found in 8% of the general population), what should be done?
Care should be taken when interpreting these results to avoid unnecessary testing
What are the 2 patterns for differential dx based on elevated LFTs?
1) Hepatocellular pattern
a. ALT-predominant
b. AST-predominant
2) Cholestatic pattern
a. Hepatobiliary causes
b. Non-Hepatic causes of elevated alkaline phosphatase
What is the condition present if hepatocellular pattern is present?
Elevated aminotransferases out of proportion to ALP
What are the conditions present in ALT-predominant?
1) Acute or chronic viral hepatitis
2) Steatohepatitis
3) Acute Budd-Chiari syndrome
4) Ischemic hepatitis
5) Autoimmune
6) Hemochromatosis
7) Medications / toxins
8) Autoimmune
9) Alpha1-antitrypsin deficiency
10) Wilson disease
11) Celiac disease
What are the conditions present in AST-predominant?
1) Alcohol-related
2) Steatohepatitis
3) Cirrhosis
4) Non-hepatic
a. Hemolysis
b. Myopathy
c. Thyroid disease
d. Exercise
What are the conditions present if cholestatic pattern is present?
Elevated ALP + GGT + bili out of proportion to AST and ALT
What are present under hepatobiliary causes?
1) Bile duct obstruction
2) Primary biliary cirrhosis
3) Primary sclerosing cholangitis
4) Medication-induced
5) Infiltrating diseases of the liver
a. Sarcoidosis
b. Amyloidosis
c. Lymphoma
6) Cystic fibrosis
7) Hepatic metastasis
8) Cholestasis
What are the non-hepatic causes of elevated ALP?
1) Bone disease
2) Pregnancy
3) Chronic renal failure
4) Lymphoma or other malignancies
5) Congestive heart failure
6) Childhood growth
7) Infection or inflammation
What are the aminotransferases?
1) AST
2) ALT
What are the fxns of AST and ALT?
1) They are the markers of hepatocellular injury
2) They participate in gluconeogenesis
How does AST and ALT participate in gluconeogenesis?
By catalyzing the transfer of amino grps from aspartic acid or alanine to ketoglutaric acid to produce oxaloacetic acid and pyruvic acid respectively
aspartic acid -> ketoglutaric acid = oxaloacetic acid
alanine -> ketoglutaric acid = pyruvic acid
What are the characteristics of AST?
1) It is present in cytosolic and mitochondrial isoenzymes
2) It is found in the:
a. Liver
b. Cardiac muscle
c. Skeletal muscle
d. Kidneys
e. Brain
f. Pancreas
g. Lungs
h. Leukocytes
i. RCs
3) It is not as sensitive or specific for the liver
4) Elevation in AST may be seen as 2ndary to nonhepatic causes as well
What are the characteristics of ALT?
It is a 1) cytosolic enzyme that is 2) found in high concentrations in the liver
What triggers the release of AST and ALT into the circulation?
Hepatocellular injury and not necessarily cell death
True or False
Both AST and ALT values are lower in normal males than females
False, because both AST and ALT values are higher in normal males than females
What are the lvls of AST and ALT of a pt that is obese (or has higher BMI)?
Both AST and ALT are higher
What are the characteristics of ALP?
1) It is part of a family zinc metalloenzymes
2) These are highly concentrated in the microvilli of the bile canaliculus as well as several other tissues (ex. bone, intestines, and placenta)
3) Normal reference range lvls also increase w/ age in females
What is the action that happens during growth?
Increased osteoblastic act
What are the ALP lvls of a pt during growth and these circumstance of ALP lvls are seen in what age grps?
The pts ALP lvls are elevated and are seen in children and adolescents
What are the characteristics of GGT?
1) It is located on membranes of cells
2) It has high secretory or absorptive activities
3) It is abundant in many other sources of the body such as:
a. Kidney
b. Pancreas
c. Intestine
d. Prostate
e. Testicles
f. Spleen
g. Heart
h. Brain
4) It is more specific for biliary disease when compared to ALP
5) GGT lvls are higher in infants
What is the main fxn of GGT?
To catalyze the transfer of a gamma-glutamyl grp from peptides to other AAs
Why is GGT more sp for biliary disease when compared to ALP?
Because it is not present in bone
What are the characteristics of bili?
1) It is the end result of heme catabolism
2) 80% of it are being derived from hgb
What is the action done in unconjugated bili (UCB)?
It is transported to the liver loosely bound to albumin
What are the characteristics of UCB?
1) It is H2O-insoluble
2) Since it is H2O-insoluble, it can’t be excreted in the urine
What are the characteristics of conjugated bili (CB)?
1) It is H2O-soluble
2) Since it is H2O-soluble, it can be excreted in the urine
Explain the process of conjugation of UCB up to its excretion?
It is conjugated in the liver to bilirubin glucuronide and subsequently secreted into bile and the gut respectively
What are the characteristics of albumin?
1) It is synthesized in the liver
2) Albumin being produced is approx 10 g per day
W/ any liver disease, what happens to serum albumin of the pt?
There is a fall in serum albumin, reflecting decreased synthesis
If liver fxn is normal and serum albumin is low, what may these reflect?
These may reflect on poor protein intake (malnutrition) or protein loss (nephrotic syndrome, malabsorption, or protein-losing enteropathy)
What is the fxn of PT?
It measures the rate of conversion of PT to thrombin
What are the coagulation factors that are synthesized in the liver?
All coagulation factors except factor VIII
What are the coagulation factors required by PT?
1) Factor II
2) Factor V
3) Factor VII
4) Factor X
Is the liver’s fxn crucial in coagulation? Why or why not?
Yes, because the coagulation factors that are required for PT are made in the liver
What is the indication if:
1) Synthetic fxn of the liver: normal
2) PT: delayed
These may indicate treatment w/ warfarin, consumptive coagulopathy (ex. disseminated intravascular coagulopathy [DIC]) or deficiency of vitamin K
Reference ranges for LFT tend to vary depending on what?
Depending on the lab
True or False
Normal reference ranges for LFTs does not vary bet males and females and may be higher for those w/ higher BMI
False, because normal reference ranges for LFTs vary bet males and females and may be higher for those w/ higher BMI
What is the reference range for ALT?
0 - 45 IU/L
What is the reference range for AST?
0 - 35 IU/L
What is the reference range for ALP?
30 - 120 IU/L
What is the reference range for GGT?
0 - 30 IU/L
What is the reference range for bili?
2 - 17 micromoles/L
What is the reference range for PT?
10.9 - 12.5 secs
What is the reference range for albumin?
40 - 60 g/L
True or False
The lvls of LFTs can point to the differentials
True
True or False
Many disease processes have very distinct abnormalities in the liver enzymes
True
What is the general ratio of AST to ALT for pts w/ alcoholism and what is its interpretation?
2:1
It shows a high lvl of AST activity in alcoholic liver disease
What is being suggested if GGT is elevated along w/ AST?
It also suggests alcohol abuse
Can GGT be used alone in terms of detecting alcohol abuse for the pt? Why or why not?
No, because GGT is not very sp for alcohol. Hence, it should not be used alone for diagnosis of alcohol abuse
What is the meaning of NSAIDs?
Nonsteroidal anti-inflammatory drugs
There are several medications that can cause liver damage. Most of these are commonly used in daily practice but not limited to what?
1) NSAIDs
2) Antibiotics
3) Statins
4) Anti-seizure drugs
5) Drugs for TB treatment
Acute hepatocellular injury can be secondary to several drugs including but not limited to what?
1) Acetaminophen
2) Allopurinol
3) NSAIDs
4) Alcohol
5) Anti-TB medications
a. Isoniazid
b. Pyrazinamide
c. Rifampin
6) Statins
7) Antifungals
a. Ketoconazole
8) Antibiotics
a. Tetracyclines
9) Anti-seizure medications
a. Valproic acid
b. Phenytoin
10) Antidepressants
a. Fluoxetine
11) Antipsychotics
a. Risperidone
12) Antivirals
a. Valacyclovir
b. Ritonavir
Acute cholestasis can be seen secondary to drugs including what?
1) Anabolic steroids
2) NSAIDs
3) Tricyclic antidepressants
4) Alcohol
5) Antibiotics
a. Azithromycin
b. Amoxicillin
c. Nafcillin
d. Rifampin
e. Trimethoprim-sulfamethoxazole
The long-term use of drugs where acute cholestasis can be seen secondary can also lead to what?
1) Chronic hepatocellular and/or
2) Cholestatic liver damage
What is the commonly used medication for rheumatoid arthritis and other inflammatory arthritis?
Methotrexate
What is the effect of methotrexate as medication for pts w/ RA and other inflammatory arthritis?
1) It can cause a mild transient elevation in LFTs
2) It can also cause permanent liver damage in liver fibrosis and cirrhosis especially w/ higher cumulative doses
Liver fibrosis can also be seen as secondary to what?
Secondary to chronic alcohol intake or methyldopa
Ergot alkaloids can result to what?
It can result in ischemic necrosis
Oral contraceptives can result in what?
It can result in hepatic venous outflow obstruction (Budd-Chiari syndrome)
Herbal medications can also cause what in LFTs?
These can also cause elevation in LFTs
What are common causes of hepatitis and elevation in LFTs?
Viral illnesses
What are the types of viral hepatitis can cause chronic hepatitis?
1) Viral hepatitis B
2) Viral hepatitis C
3) Viral hepatitis D
What are the types of viral hepatitis that can cause acute viral hepatitis?
1) Viral hepatitis A
2) Viral hepatitis E
What are the other viruses that can also cause hepatitis?
1) HIV
2) Epstein-Barr (EBV)
3) Cytomegalovirus (CMV)
What type of disease is autoimmune hepatitis?
It is a chronic disease
What are the characteristics of autoimmune hepatitis?
1) It is characterized by continuing hepatocellular inflammation
2) It is characterized by having necrosis
3) It has a tendency to progress to cirrhosis
4) It is more common in young women than men w/ a 4:1 ratio
5) The pt having autoimmune hepatitis usually presents w/ high LFTs w/out apparent cause
What are the characteristics of pts w/ autoimmune hepatitis?
These pts can have:
1) (+) autoAbs
a. Antinuclear Ab
b. Anti-smooth muscle Ab
c. Anti-liver / kidney microsomal Abs
d. Abs to the liver Ag
What is the other term for fatty liver disease?
Nonalcoholic steatohepatitis
Fatty liver disease has gained more attention recently because what?
Because of its ability to cause chronic hepatic disease as well as hepatocellular carcinoma (HCC)
What are the characteristics of pts w/ fatty liver disease?
1) Pt is overweight
2) Pt has type II diabetes or
3) Pt has dyslipidemia
4) Pt has no evidence of clinically significant alcohol use
5) Pt’s AST and ALT are usually both elevated w/ a ratio of 1:1, w/ other LFTs being normal
What is hemochromatosis?
It is the abnormal accumulation of Fe in parenchymal organs, leading to organ toxicity
What are the characteristics of hemochromatosis?
1) It is the most common autosomal recessive genetic disorder
2) It is the most common cause of severe Fe overload
What are the clinical manifestations of a pt w/ hemochromatosis?
1) Diabetes
2) Liver disease
3) Cutaneous hyperpigmentation
What is the condition for possible hemochromatosis?
A raised serum ferritin lvl
Compared to a raised serum ferritin level, what condition is more reliable when it comes to possible presence of hemochromatosis?
A transferrin saturation 45% >
What are the 2 HFE mutations?
1) C282Y
2) H63D
What is the purpose of HFE mutations?
These are pivotal for the dx of hereditary hemochromatosis
Secondary hemochromatosis can also be seen due to what?
Increased Fe intake
What is Wilson disease?
It is a rare autosomal-recessive inherited disorder of copper metabolism
What are the characteristics of Wilson disease?
It is characterized by excess copper deposition in the:
1) Liver
2) Brain
3) Other tissues
True or False
It is okay even if Wilson disease is not recognized and treated early because it is not fatal
False, because if Wilson disease is not recognized and treated early, it is fatal
What are the characteristics (in relation to clinical dx) of Wilson disease?
1) A low ceruloplasmin lvl is seen in the majority (up to 85%) of the cases
2) Presence of Kayser-Fleischer rings can serve as a clinical clue but is not present all the time
3) The 24-hr urinary copper excretion test is usually abnormal w/ 100 micrograms > of copper excretion in the urine indicating Wilson’s disease
What is the confirmatory test for Wilson’s disease?
Liver biopsy
What is the meaning of AATD?
Alpha-1 antitrypsin deficiency
What are the characteristics of AATD?
1) It is a relatively common yet often undiagnosed genetic condition
2) It is 1 of the most common inherited disorders among Caucasians
Pts w/ AATD are also predisposed w/ what?
1) Obstructive pulmonary disease
2) Liver disease
a. Cirrhosis
b. Hepatocellular carcinoma
- > In children
- > In adults
What is the primary manifestation of AATD?
Early-onset panacinar emphysema
