4- LFTs Flashcards
what are liver enzymes in liver biochemical tests?
- alanine aminotransferase (ALT)
- aspartate aminotransferase (AST)
- alkaline phosphatase (ALP)
- gamma glutamyl transferase (GGT)
what are liver function tests?
- bilirubin
- albumin
- prothrombin time
what are transaminases?
same as aminotransferases = ALT & AST are main ones
when is ALT & AST released?
damage to hepatocytes
along with being found in liver - where else can ALT and AST be found?
- ALT found in low concentrations in muscle & kidney
- AST found in cardiac & skeletal muscles, kidney, pancreas and RBC’s
with ALT 50-200 = what can be causes?
= MASLD, chronic viral hepatitis
(can be autoimmune hepatitis, hereditary haemochromatosis, wilson’s disease, alpha 1 antitrypsin deficiency)
with ALT 1000 = what can be causes?
- viral hepatitis
- shocked liver (hypotension from sepsis etc→shock)
- paracetamol overdose
- autoimmune hepatitis
- Budd-Chiari
with ALT 3000 = what can be causes?
drug (paracetamol) or ischaemia
are both ALT and AST always elevated together?
no, in hepatitis C virus & fatty liver ALT can be elevated and not AST
(AST is found in lots more other places so when localised inflammation might not elevate)
by how much does ALT rise in alcoholic hepatitis?
no more than 3 x upper limit of normal
what biochemical tests are different in acute biliary obstruction?
ALT increased and then later increased ALP as a result of bile duct obstruction
what is normal AST:ALT ratio?
usually <1
what is AST:ALT ratio in fibrosis?
in fibrosis >1
what is AST:ALT ratio in alcoholic liver disease?
AST 2x > ALT in alcohol related liver disease
what is alkaline phosphatase (ALP)?
biliary enzyme that is in liver, placenta and bone, kidney & intestine
where is alkaline phosphatase in liver?
present on canicular epithelia = increase bile salts leads to increased release from cell surface →marker of biliary tree irritation (blockage means rises & falls slower)
when does ALP in placenta increase?
increases 2x more than upper limit of normal which may persist for a few weeks pas delivery
what does ALP correlation with GGT reveal?
increase in ALP and GGT reveals biliary source
what is gamma glutamyl transferase?
biliary enzyme that is excreted in bile in hepatocytes & biliary epithelial cells
how is GGT related to alcohol?
it can be induced in alcohol (released)
= not definitive diagnostic of alcohol through as other reasons too
= once stop drinking, levels drop
what can increase release of GGT?
- alcohol
- enzyme inducing medications like anticonvulsants (phenytoin, barbiturate)
- increase in serum liver disease
what is unconjugated bilirubin and causes?
indirect bilirubin
causes:
- haemolysis
- haematoma resorption
- gilbert’s syndrome
what is conjugated bilirubin and causes?
direct bilirubin
causes:
- biliary pathology
- hepatitis
- cirrhosis
- drug toxins
- TPN
what are episodes of jaundice precipitated by?
- Fasting
- Hemolysis
- Intercurrent febrile illnesses
- Physical exertion
- Stress
- Mense
where is albumin synthesised and what’s function?
- synthesised by liver
- transports insoluble bilirubin, hormones, fatty acids
what causes albumin synthesised?
- end stage liver disease
what is prothrombin time?
a part of liver function test = increased prothrombin time related to decreased synthesis of clotting factors (fibrinogen II, V, VII, X)
- used to assess coagulation pathways
what is example of acute liver injury that increases prothrombin time?
- Massive hepatocellular necrosis (acute toxic or viral hepatitis) →↑ prothrombin time
- Prothrombin time can be monitored in order to assess the risk of acute liver failure.
what effect does chronic liver disease have on prothrombin time?
long PT
what viruses are involved in liver screen?
viral hepatitis serology:
- Hep B & C serology
- hep A & E
other viruses:
- epstein barr virus (EBV)
- cytomegalovirus (CMV)
- Herpes SImplex Virus (HSV)
what autoimmune markers are checked for in liver screen?
- antinuclear antibodies
- anti-smooth muscle antibodies
- anti-liver/kidney microsomal antibodies type 1 (anti-LKM1)
- Antimitochondrial antibody (AMA)
- Immunoglobulins = IgG, IgM and IgA
what haematinics is checked for in liver screen?
- TSATs> 45% for women or 55% for men (transferrin saturation)
- Ferritin >200ng/ml or >300ng/ml for men
what are tested for in liver screens?
- viral hepatitis serology
- other viruses
- autoimmune markers
- haematinics
- caeruloplasmin
- alpha 1 antitrypsin
what are 3 main patterns to think about to decipher abnormal LFTs?
- hepatitis →problem with liver parenchyma
- cholestatic →problems with bile duct
- mixed
for autoimmune hepatitis
a) most common gender
b) symptoms
c) what age
a) females
b) asymptomatic or non specific symptoms
c) peaks around puberty and between 4th &6th decade
what is involved in diagnosis of autoimmune hepatitis?
- hepatitic LFTs
- increased IgG
- autoimmune profile →either type 1 (anti-SMA, ANA) or 2 (anti-lkm-1, antiLC1)
- liver biopsy
what is treatment of autoimmune hepatitis for acute and maintenance ?
acute = prednisolone (milder = budesonide)
maintenance = azathioprine (immunosuppressant)
what viral infections can cause liver failure?
- hepatitis A-E
- epstein barr virus, cytomegalovirus, herpes simplex virus
what are liver function tests in MASLD and what is MASLD?
MASLD = Metabolic dysfunction-associated steatotic liver disease
- ALT is usually elevated, while AST:ALT ratio >1 suggests advanced fibrosis.
- ALP and GGT levels may be increased.
- Serum bilirubin and albumin levels are typically normal.
what is onset of alcoholic hepatitis?
onset of jaundice and/or ascites in a patient with ongoing alcohol misuse/recent cessation
what are assessment scores to be used in alcoholic hepatitis?
- maddrey’s discriminant function = >32 correlated 45% mortality at 28day
- glasgow hepatitis score = composite score ≥9 28 day survival much worse
what is treatment of alcoholic hepatitis?
prednisolone can be beneficial in short term mortality but not for any longer than that = treatment depends on individual clinicians
- can use neutrophil lymphocyte ratio to see if will benefit
what are cholestatic liver test?
= tests to assess liver function & identify conditions associated with impaired bile flow from the liver
what is colicky pain often associated with?
gallstones
what is MRCP?
MRCP stands for Magnetic Resonance Cholangiopancreatography. It is a non-invasive imaging technique that uses magnetic resonance imaging (MRI) to visualize the bile ducts, pancreas, and pancreatic ducts. MRCP is particularly useful in evaluating the biliary tree
what is primary biliary cholangitis?
a chronic autoimmune liver disease characterized by progressive destruction of the small bile ducts within the liver
- associated with systemic sclerosis
what are symptoms & signs of primary biliary cholangitis?
Symptoms:
- Itch
- Lethargy
- Dry eyes
Signs:
- Xanthesalma and xanthomas
what is pathophysiology of primary biliary cholangitis?
- coordinated T&B cell mediated autoimmune cascade with T cell mediated BEC injury
- loss of protective bicarbonate rich umbrella around BECs and gradua loss of bile ducts
- progressive inflammation & biliary fibrosis
- cholestasis
what is treatment of primary biliary cholangitis?
1st line: Ursodeoxychloic acid
what is primary sclerosing cholangitis?
chronic inflammatory liver disease characterized by progressive inflammation and fibrosis of the bile ducts both inside and outside the liver
what is seen on MRCP for diagnosis of primary sclerosing cholangitis?
= multiple segmental strictures with dilated intrahepatic and extrahepatic ducts
what is seen on biopsy for diagnosis of primary sclerosing cholangitis?
ductopenia, bile duct proliferation, and periductal fibrosis, with an onion-skin fibrosis and nodular fibrous scars
what is treatment for primary sclerosing cholangitis?
no treatment →try manage stricture, survey for gallbladder and colorectal cancer in IBD survey
what mostly causes mixed pattern of LFTs?
drugs! - any drugs but commonly
- Hepatitis (isoniazid, phenytoin, methyldopa)
- Cholestasis (augmentin, ocpill, androgens)
- Steatosis (TPN, methotrexate)
what are other causes of mixed LFTs?
- hereditary haemochromatosis (excess iron deposition, high ferrin & transferrin)
- wilsons disease (excess copper deposition, low ceruplasmin liver screen)
- budd chiari (hepatic vein occlusion, seen on doppler US)
- pregnancy (cholestasis or acute fatty liver)
what are principles of investigation for abnormal LFTs?
- history
- examination
- liver screen & AUSS
= use pattern to develop likely aetiology
generally for acute hepatitis, are the following increased, decreased or normal
a) ALT
b) ALP
c) GGT
d) bilirubin
a) increased
b) normal or increased
c) normal or increased
d) increased
generally for chronic hepatitis, are the following increased, decreased or normal
a) ALT
b) ALP
c) GGT
d) bilirubin
a) normal or increased
b) normal or increased
c) normal or increased
d) normal or increased
generally for cholestatic, are the following increased, decreased or normal
a) ALT
b) ALP
c) GGT
d) bilirubin
a) normal or increased
b) increased
c) increased
d) normal or increased
