tbl 5 clinical: interpreting LFTs Flashcards
Liver function test (LFT) – constellation of enzymes and protein readings which reflect liver condition.
- Measures enzymes that liver and bile duct cells release in response to damage or disease (ALT, AST, ALP, GGT)
- Some tests measure functions of liver such as albumin production, bilirubin clearance and coagulation (ALB, BIL, PT/INR)
o ALT, AST is produced by damaged hepatocytes while ALP, GGT, bilirubin can indicate __________, bile duct obstruction and liver injury - In hepatology, the most accurate way to diagnose liver disease in a patient is _____________________ (not practical in daily clinical work)
o Non-invasive assessments such as blood biomarkers (LFT in this instance) is a useful indicator of liver pathophysiology
o When used in the appropriate clinical context, LFT can be a powerful tool that indirectly reflects liver pathology, avoiding the need of liver biopsy.
o LFT is a simple blood test and avoids the risk of liver biopsy such as pain, organ injuries and bleeding
cholestasis;
obtaining liver tissue through liver biopsy and resection;
General approach to LFT interpretation
- Before interpreting LFT, need to make sure there are no confounders that can affect the report of LFT – certain factors can lead to abnormal LFT and it may not reflect true underlying liver pathology
- Quality of blood taking – _____________ blood sample will affect the bilirubin report
- Co-morbidities
o Proteinuria, malnutrition, _______ reduces albumin
o Background history of thalassemia or haemolytic disorders increases bilirubin level
o Other organ sources that can affect the enzymes levels - To be a good interpreter, an understanding of liver pathophysiology, differential diagnosis, and iatrogenic intervention is essential
o ___________ over time may give information to the patient’s baseline, disease progression and response to treatment
o e.g. chronic liver disease in chronic hepatitis B is typically of a relapseremitting nature – fluctuation of ALT over time
o Pattern recognition is the fundamental skill required
septicaemia;
haemolysed;
Serial LFTs
Severity of transaminitis (transaminase elevation) and differential diagnosis
- The degree of transaminases elevation may indicate underlying liver injury aetiology
- Acute hepatitis – defined as ALT or AST level >1,000 U/L
o Consider 3 common diagnosis for acute hepatitis – viral hepatitis, drug-induced liver injury (DILI), ischaemic hepatitis - Different diagnosis of liver disease based on lower elevation of transaminases
- The magnitude of transaminases elevation serves as only a general guide of potential aetiology
o Need to consider further LFT to establish a trend – may not be reading an LFT taken during the peak of liver injury
o In the meantime, interpret results by taking into account the clinical scenario as you may need to initiate early treatment or further important investigation - Minor elevation (<100 U/L): ???
- Moderate elevation (100 to 300 U/L): Alcoholic hepatitis, ____________, Autoimmune hepatitis
- Severe elevation (>300 U/L): ____________, Hepatitis B flare
Chronic hepatitis B or C, Fatty liver; Statins;
Non-alcoholic steatohepatitis;
Drug Induced Liver Injury
Upper limit of normal (ULN) of transaminases in LFT – different laboratories have different normal ranges of LFT enzymes
- Due to the calibration of the LFT reference range using blood from healthy local population e.g. bloods from blood donors
- Factors such as undiagnosed liver disease and recent medication consumption may affect liver enzyme calibration and thus its validity
- Internationally, the upper limits of normal (ULN) for ALT in healthy adults are reported to be ________ U/L for males and _______ U/L for females.
o It has to depend on the clinical context a clinician is discussing as a significant ULN may be different between disease entities based on the statistical correlation of outcome
- For purposes of guiding management of Chronic HBV, a ULN for ALT of 35 U/L for males and 25 U/L for females is recommended
Quantification of severity of transaminases elevation – can be used for both the hepatocellular injury and the cholestasis component
Magnitude of liver enzymes elevation Interpretation Guide
- 1x to 2x ULN: Mild
- 2x to 5x ULN: Moderate
- 5x to 10x ULN: Moderate-severe
- > 10x ULN: Severe
- Significant elevation of transaminases must be viewed in the appropriate clinical context
- e.g. in chronic hepatitis B, a __________ of ALT together with HBV viral load is an important decision point
29 to 33;
19 to 25;
2x ULN
Classification of liver injury – based on predominant liver enzymes involved
- Categorising liver injury into hepatocellular predominant, cholestatic predominant of liver injury – based on predominant liver enzymes involved
- Categorising liver injury into hepatocellular predominant, cholestatic predominant,
mixed picture or infiltrative nature may guide in differential diagnosis
Result Interpretation
- ALT and AST > ALP: ________ predominant
- ALP > ALT and AST: _________ predominant - bile duct diseases such as primary biliary cholangitis
- ALT and AST = ALP: Mixed picture
- ALP elevation, Near normal or normal ALT and AST: ____________
- It is not uncommon to have both components of hepatocellular injury and cholestasis in a single disease entity – underlying liver inflammation affects both hepatocytes and bile duct cells
o Especially common in severe liver inflammation such as acute hepatitis in which the LFT often shows significant elevation of both components
o However it is still hepatocellular injury predominant
Hepatocellular injury ;
Cholestasis;
Infiltrative disease;
AST/ALT Ratio and its reverse AST/ALT ratio Interpretation
- > 2: Very likely alcohol related
- 1 to 2: Probable alcohol related – especially in a setting with ____________
- < 1 Unlikely alcohol related
- AST/ALT ratio has been traditionally used to exclude active alcohol intake
o In a clinical context, this ratio together with GGT and ___________ can be used to exclude significant alcohol consumption
o Compared to ALT and AST, GGT will show the largest increase
- In healthy humans, AST is usually higher than ALT – if ALT/AST < 1, it may suggest underlying liver cirrhosis
raised GGT;
macrocytosis
