lfts
Table of Contents
liver function tests (LFTs)
introduction
- liver functions tests are commonly ordered as a screening test for patients with upper abdominal pain, jaundice (icterus), or for a variety of other presentations.
- ALT and AST are the main markers of liver damage, although thse can also be raised in muscle damage conditions
- glutamate dehydrogenase (GLDH) is a more liver-specific biomarker for detecting liver injury but is not currently available as a test 1)
- bilirubin, AP and GGT tend to be raised in cholestatic conditions but can be raised due to other conditions
- serum albumin falls as a marker of acute phase reactions such as severe infection, but can also fall due to many other conditions (decreased production, increased renal protein losses, etc)
Abnormal LFTs
- LFTs may be abnormal for a range of aetiologies which can generally be grouped as follows:
- acute hepatocyte damage:
- this may be due to a viral or drug induced hepatitis, bacterial infections such as:
- drug induced: alcohol, paracetamol overdose, etc
- ischaemic hepatitic necrosis
- severe congestive cardiac failure
- rarely, Budd-Chiari syndrome (BCS)
- the LFT's generally show a “hepatitic picture” of elevated ALT and AST (particularly if 10-fold increase compared to less than 2 fold increase in AP and GGT) +/- raised bilirubin with lesser or no elevations in GGT or AP
- most of these conditions cause a similar rise in BOTH AST and ALT
- levels > 50 fold increase may be seen in ischaemic hepatitic necrosis
- levels > 25 fold increase often occur in viral or drug-induced hepatitis
- acute liver failure typically is characterised by increases > 10-fold, plus abnormal clotting time
- non-alcoholic fatty liver and haemochromatosis usually has < 4-fold increase
- chronic hepatitis C infection usually has a < 2-fold increase but may be up to 10-fold increase
- alcoholic liver disease may see rises up to 8-fold for AST and 5-fold for ALT
- hepatitic picture with thrombocytopenia:
- viral haemorrhagic fevers and similar such as Severe fever with thrombocytopenia syndrome virus (SFTSV)
- bile obstruction picture:
- this is usually due to cholelithiasis but may occur with some drugs, particularly, alcohol, and from external compression on biliary tree such as via neoplasia / cancer / tumours
- the LFT's generally show a “cholestatic picture” of elevated AP and GGT +/- raised bilirubin with lesser or no elevations in ALT or AST
- impaired liver function:
- this is generally demonstrated by a low albumin level (impaired synthesis capability) often with raised bilirubin +/- impaired clotting ability (impaired synthesis capability of clotting factors)
- rarely, Budd-Chiari syndrome (BCS)
- “mixed picture” abnormal LFTs:
- often the LFTs show a general increase in all four enzymes tested and this picture can be caused by aetiologies which cause either the hepatitic or cholestatic pictures
- NB. consider using a lower than “normal” range for patients on haemodialysis
Ix of the patient with "hepatitic picture"
- is there an obvious cause
- acute alcohol intake or picture of chronic alcohol abuse (AST:ALT ratio, history, etc)
- pregnant:
- overseas travel with fever:
- etc
- gastroenteritis:
- hepatic venous congestion:
- drug and alcohol history
- if raised ALT with eosinophilia:
- consider drug reaction with eosinophilia and systemic symptoms (DRESS) - usually starts 2-6wks after starting drug
- serology for viral hepatitis, EBV / glandular fever / infectious mononucleosis, consider cytomegalovirus (CMV)
- is patient obese and USS confirms non-alcoholic fatty liver disease
- if the above are non-diagnostic then:
- iron studies to exclude haemochromatosis - suggested by transferrin saturation > 45% and high ferritin levels
- hepatobiliary USS +/- CT scan to exclude neoplasia / cancer / tumours, etc.
- re-check LFTs in 3-6 months
- if LFT's still deranged and no diagnosis then:
- serum protein electrophoresis and if +ve, then ANA, anti-smooth muscle Abs, anti-liver/kidney microsomal Abs
- TSH to exclude hypothyroidism and hyperthyroidism
- consider coeliac disease, Wilson's disease
- if LFT's persistently > 2-fold higher than normal, then consider liver biopsy although low yield and not without risks
- still non-diagnostic consider referral or search for even more obscure diseases such as adrenal insufficiency
Ix of the patient with a "cholestatic picture":
- the most common cause of “cholestatic picture” is biliary, thus a biliary USS is indicated to exclude cholelithiasis (gallstones) or CBD obstruction due to other causes
- USS shows dilated CBD:
- extrahepatic cholestasis is the most likely cause of the abnormal LFTs and suggests conditions such as:
- Mirizzi syndrome (impacted cystic duct stone pressing on the CBD)
- primary sclerosing cholangitis with an extrahepatic bile duct stricture
- AIDS cholangiopathy
- if biliary USS normal:
- it may still be extrahepatic cholestasis with normal CBD and intrahepatic duct diameters if either:
- partial obstruction of the bile duct
- scarred ducts preventing the ducts from dilating
- eg. cirrhosis or primary sclerosing cholangitis
- causes of intrahepatic cholestasis:
- primary biliary cirrhosis (PBC) - check antimitochondrial antibodies and if +ve, consider liver biopsy
- primary sclerosing cholangitis - consider MRCP to Dx
- infiltrative diseases:
- sarcoidosis, other granulomatous diseases, amyloidosis
- drug toxicity
- viral hepatitis
- cholestasis of pregnancy
- benign postoperative cholestasis
- total parenteral nutrition
Ix of isolated raised GGT
- an isolated raised GGT levels is usually not worth extensive Ix as it tends to be non-specific and occurs in:
- pancreatic disease
- myocardial infarction
- renal failure
- chronic obstructive pulmonary disease
- diabetes mellitus
- alcoholism
- patients taking medications such as phenytoin and barbiturates
Ix of isolated raised AP
- exclude raised AP arising from bone:
- children and adolescents with rapidly growing bones
- those with healing bone fractures
- those with bone disorders such as osteomalacia, etc.
- these patients may require work up for these bone conditions
- isolated raised AP arising from the liver may occur in:
- intrahepatic cholestasis (see above under Ix of cholestatic picture)
Ix of isolated hyperbilirubinaemia
- see also jaundice (icterus)
- determine if bilirubin is mainly:
- conjugated (“direct hyperbilirubinaemia”):
- due to:
- decreased excretion into the bile ductules
- Dubin-Johnson syndrome
- leakage of conjugated bilirubin from hepatocytes into serum
- Rotor syndrome
- unconjugated (“indirect hyperbilirubinaemia”):
- due to:
- bilirubin over-production:
- haemolysis
- haemolytic anaemia - check urine for Hb, and check blood reticulocyte count
- emphysematous cholecystitis - mild to moderate unconjugated hyperbilirubinemia may be present because of haemolysis induced by clostridial infection
- ineffective haematopoiesis
- impaired bilirubin uptake into liver or conjugation:
- Gilbert's disease (especially during periods of stress)
- Crigler-Najjar syndrome
- drugs
Ix of isolated hypoalbuminaemia
- see hypoalbuminaemia and nephrotic syndrome
lfts.txt · Last modified: 2025/03/29 02:43 by gary1