Liver Function Tests (from Australian Family Physician | P) Flashcards
What are LFTs?
These are a panel of markers
What is the fxn of LFTs?
These are used to assess and monitor several diseases
Are all LFTs considered as true tests of liver function?
No, not all LFTs are true tests of liver function
Are abnormalities present in the human body may reflect presence of liver disease?
No, abnormalities may not reflect liver disease
What are the indications for liver fxn testing?
1) Investigating and monitoring pts w/ suspected liver disease
2) At risk pt grps
3) Monitoring malignancy
4) Before initiating and monitoring hepatotoxic medications
True or False
There is no cost effectiveness data for the use of LFTs
True
What is the percentage of the population w/c may have an abnormal result (usually mild) at any 1 time?
2.5% of the healthy population
Is a blood test required for LFTs?
No
Is special preparation such as fasting necessary for LFTs?
No
Results for LFTs are often available in what time duration?
Within 24 hrs
At what areas / situations are the release of results for LFTs slower?
Results may be slower in remote areas
At what areas / situations are the release of results for LFTs quicker?
Results may be quicker in urgent situations
LFTs attract a what?
Medicare rebate
Enzyme GGT, ALP, AST, and ALT involve a what?
Monitored rxn
Rarely, enzymes may form what w/ Igs or other large molecules?
Macro complexes
Enzymes that may form macro complexes w/ Igs / other large molecules results in what?
Reduced clearance and a falsely high result
What is the result if substrate exhaustion is present in pts w/ extremely high enzyme lvls?
It may lead to a falsely low result
Why should sxs w/ high bili being suspected be protected from light?
To prevent degradation
If the sx is hemolyzed, some methods give what type of results?
Falsely low results
Serum albumin is routinely measured by what?
Dye binding
The diff dyes being used has what?
Variable specificity, particularly in the low range
For repeat testing (or tests), what is preferred to be done and why is it preferred to be done?
It is preferred to use or to test in a same lab because the diff dyes that are used has variable specificity, particularly in the low range
It is helpful to classify results as what?
1) A typical of cholestasis
2) Consistent w/ hepatocellular damage
What is cholestasis?
It is the interruption to the bile flow bet the hepatocyte and the gut
What are the transaminases?
1) AST
2) ALT
Raised transaminases suggests what?
Hepatocellular injury
Marked increases (over 10 times the URL) of transaminases suggests what?
1) Acute
2) Severe insult (ex. drugs)
3) Acute viral hepatitis
4) Hypoxia
Mildly elevated transaminases (up to 5 times the URL) suggests what?
1) Infection
2) Alcohol
3) Fatty liver
4) Due to medications
Alcohol often results in what?
Higher AST:ALT ratio than other forms of liver damage
True or False
Transaminase lvls directly correlate to the degree of liver damage
False, because transaminase lvls do not directly correlate to the degree of liver damage
Provide an ex of transaminase lvls that do not correlate to the degree of liver damage
In cirrhosis, transaminase lvls may drop to within the reference range
What is the characteristic of ALP?
It is not sp to the liver
Where is ALP produced?
1) Bone
2) Intestine
3) Placenta
A concurrent raise of GGT lvls suggests what?
Liver origin
What are the common causes of a raised ALP and GGT?
1) Cholestasis
2) Enzyme induction by alcohol
3) Medication
Isolated raised ALP is typically due to what?
Bone disease
Provide exs of bone disease where isolated raise of ALP lvls is present
1) Paget disease in pts over the age of 50 yrs
2) Vitamin D deficiency
3) Metastasis
Can the lab quantify ALP liver and bone isoforms?
Yes
On request, when may the lab quantify ALP liver and bone isoforms?
1) If the clinical context is unclear
2) When the total ALP is over 1.5 times the URL
GGT is most useful to what?
To confirm the liver origin of ALP
GGT is associated w/ what?
Alcohol use
What is the percentage of isolated raised GGT that is due to alcohol excess?
Only 70%
What is the percentage of alcohol abusers who have a normal GGT?
30%
GGT lvls remain elevated for what time duration after cessation of heavy drinking or liver injury?
GGT lvls remain elevated for 2 - 3 wks
At what conditions / disorders are bili lvls increased?
1) Cholestatic disease
2) Hepatotoxic liver disease
In adults, raised bili lvls is usually what?
Predominantly conjugated
The presence of unconjugated hyperbilirubinemia in adults is usually due to what conditions / disorders?
1) Gilbert syndrome
2) Hemolysis
What is Gilbert syndrome?
It is a common benign impairment in bili conjugating ability
What percentage of the population is affected by Gilbert syndrome?
Up to 5%
What is associated for the up to 5% of the population who are affected by Gilbert syndrome?
These percentage of the population are associated w/ a persistent isolated increase in bili up to 2 - 3 times the URL
GGT lvls increase during what disorders / conditions?
1) Acute illness
2) Fasting
Low albumin lvls can indicate what disorder / condition?
Severe liver disease
Presence of low albumin lvls are more often from / due to what causes?
1) Physiological (pregnancy)
2) Inflammation
3) Malnutrition
4) Protein losing states
Total protein can be useful to estimate what?
1) Globulin fraction
2) Increased in inflammation
In cirrhosis, low albumin and increased bili are associated w/ what?
Reduced survival
Interpretation and follow up vary w/ what?
Clinical context and results
In selected settings, isolated, unexpected minor abnormalities may be repeated within what duration of time frame?
Short time frame (ex. 1 wk)
What is the distribution of the results that will return to normal range on repeat testing?
Almost a third of results
What is the more likely cause of persistent abnormality of LFTs lvls?
More likely to be due to significant pathology
What should be the frequency of monitoring pts w/ existing liver disease / hepatotoxic effects of medications if the pt is stable?
It should be done no more than monthly
If the pt intakes methotrexate, what should be the frequency of testing?
3 monthly testing
At what conditions / disorders is daily testing may be appropriate?
1) Very acute toxic conditions
2) Hypoxic insult
In acute toxic conditions and in cases of hypoxic insult, what is the more common frequency of testing in these conditions / disorders?
Twice weekly
What is the characteristic of transaminases?
They have large normal within-subject variability
Serial results of transaminases are only significant if they differ by what?
30% >
Serial results of GGT lvls are only significant if it differ by what?
20% >
Serial results of ALP lvls are only significant if it differ by what?
15% >
Serial results of bili lvls are only significant if it differ by what?
40% >
In connection to significant changes being present in cases of serial results in diff LFTs, what is the characteristic of albumin?
It has a very low intraindividual variation
Who are the pts where follow up investigations are certainly recommended?
1) Pts w/ severe or persistent abnormalities
2) Pts w/ relevant clinical findings
The follow up investigations for the given pts are what?
Context sp
What are the 1st line in terms of follow up investigations in a hepatotoxic picture?
1) Hepatitis serology
2) Ferritin saturation
3) Transferrin saturation
What are the less common causes where further investigation (whereas tests may be utilized) is needed?
1) Copper overload
2) Autoimmune liver disease
What is the usual test / procedure for the initial emphasis for cholestatic results?
Hepatic imaging w/ ultrasound
What are the sites of origin of the given LFT?
Given LFT: Bili
1) Heme metabolite
2) Conjugated in liver
What is the site of origin of the given LFT?
Given LFT: Albumin
Synthesized in liver; half life: about 20 days
What is the site of origin of the given LFT?
Given LFT: Total protein
Includes albumin, Igs, and carrier proteins; variable proportion synthesized in liver
What is the site of origin of the given LFT?
Given LFT: GGT
Originates from the canalicular (bile) surface of hepatocyte
What are the sites of origin of the given LFT?
Given LFT: ALP
1) Originates from the canalicular (bile) surface of hepatocyte
2) Also from bone (produced during bone formation),
3) Intestine, &
4) Placenta
What are the sites of origin of the given LFT?
Given LFT: AST
1) Hepatocyte cytoplasm
2) Hepatocyte mitochondria
3) Muscle
a. Skeletal
b. Cardiac
What is the site of origin of the given LFT?
Given LFT: ALT
Originates from the hepatocyte cytoplasm
What are the exs for the given indication of LFT?
Given indication of LFT: History or examination findings suggest liver disease
1) History of poisoning (ex. paracetamol)
2) Jaundice on examination
3) History of alcohol abuse
4) Signs of chronic liver disease including ascites
5) Family history of hemochromatosis
What are the exs for the given indication of LFT?
Given indication of LFT: Screening for populations at high risk of blood borne virus infection
1) Contact tracing in cases of hepatitis
2) Indigenous pts
3) Illicit drug use
4) Previous transfusion
What are the exs for the given indication of LFT?
Given indication of LFT: Significant nonliver disease that may effect liver function
1) Malignancies
2) Hypoxia
What are the exs for the given indication of LFT?
Given indication of LFT: Monitoring medications
1) Valproate
2) Methotrexate
What are the lab features present for the given pattern for liver disease?
Given pattern: Cholestasis
1) ALP > 200 IU/L
2) ALP more than 3 times > ALT
What are the lab features present for the given pattern for liver disease?
Given pattern: Hepatocellular damage
1) ALT > 200 IU/L
2) ALT is more than 3 times > ALP
What are the common causes of the given pattern for liver disease?
Given pattern: Cholestasis
1) Biliary obstruction
2) Pregnancy (needs further assessment)
3) Drugs (ex. erythromycin and oestrogen)
4) Infiltration (ex. malignancy)
What are the common causes of the given pattern for liver disease?
Given pattern: Hepatocellular damage
1) Infection (ex. hepatitis B, C, A; EBV; CMV)
2) Alcohol (AST often > 2 times ALT)
3) Fatty liver
4) Drugs (ex. paracetamol)
5) Metal overload (ex. hereditary hemochromatosis, and copper overload)
6) Hypoxia (LD usually > 1.5 times AST)
7) Autoimmune
Pts w/ pre-existing liver disease, including alcohol abuse are vulnerable to what?
Paracetamol, even at a std dose
Case study
A woman, 35 yrs of age, complained of abdominal pain and dark urine. She was clinically mildly jaundiced. Her liver function tests were as follows:
Albumin = 36 g/L (34 - 48) Protein = 83 g/L (65 - 85) Total bilirubin = 45 umol/L (2 - 24) GGT = 439 U/L (< 60) ALP = 285 U/L (30 - 110) ALT = 49 U/L (< 55) AST = 43 U/L (< 45)
Provide points for analysis
1) Raised ALP relative to ALT suggests cholestasis
2) High GGT confirms liver origin
3) The mild hyperbilirubinemia confirms the clinical impression of jaundice
4) Biliary disease is highly likely w/ gallstones the most likely differential dx
5) This clinical pic may also occur in drug rxns / infiltrative conditions
6) After a careful history, abdominal ultrasound is the most appropriate next investigation
Case study
A man, 38 yrs of age, had the ff results as part of an insurance medical:
Albumin = 37 g/L (34 - 48) Protein = 72 g/L (65 - 85) Total bilirubin = 13 umol/L (2 - 24) GGT = 46 U/L (< 60) ALP = 81 U/L (30 - 110) ALT = 76 U/L (< 55) AST = 44 U/L (< 45)
Provide points for analysis
1) Mild elevation in transaminases is not an uncommon incidental finding in asymptomatic pts
2) The commonest causes include chronic hepatitis C infection (affecting up to 3% of the population), fatty liver, and hereditary hemochromatosis
3) Alcohol use should be reviewed as alcoholic hepatitis and nonalcoholic steatohepatitis have almost identical biochemical and clinical presentations
4) There’s no biochemical test to reliably identify or exclude alcohol abuse
5) Overweight and obesity increase the risk of fatty liver by six-fold but need not be present to make the dx
6) Ultrasound shows a bright hyperechoic liver texture, as typically seen in fatty liver
What are the things that should be done to all pts w/ mildly elevated transaminases?
1) They should be asked about risk factors for blood borne infections
2) They should have serological testing for hepatitis C and B
What is the frequency of hereditary hemochromatosis in Australia?
1:150
What is the percentage of men that are homozygous for the most common HFE gene mutation that will become overloaded?
Only 28% of men
What is the percentage of women that are homozygous for the most common HFE gene mutation that will become overloaded?
1% of women
Since the most common HFE gene mutation will become overloaded in certain percentage of men and women, what is recommended?
Initial screening w/ fasting iron studies for ferritin and transferrin saturation is recommended
Case study
A man, 66 yrs of age, presented w/ weight loss and fatigue. He had a normocytic anemia. His LFTs were as follows:
Albumin = 22 g/L (34 - 48) Protein = 59 g/L (65 - 85) Total bilirubin = 12 umol/L (2 - 24) GGT = 926 U/L (< 60) ALP = 527 U/L (30 - 110) ALT = 104 U/L (< 55) AST = 96 U/L (< 45)
Provide points for analysis
1) The raised ALP relative to ALT suggests cholestasis in the absence of jaundice
2) While medications may be responsible, pt’s age, significant symptoms and low albumin (biochemical evidence of severe concurrent illness) suggest intrahepatic cholestasis from liver metastases as a likely cause
3) It would be unusual for this to be the 1st indication of neoplastic disease
4) As in many cases of cholestasis, ultrasound is an appropriate next investigation
