Conditions Affecting LFTs Flashcards
What are the LFTs?
- Bilirubin (BR)
- Alkaline phosphatase (AP)
- Alanine transaminase (ALT)
- Aspartate transaminase (AST)
- Gamma GT (GGT)
- Albumin
Which LFTs rise in hepatitis?
ALT and AST
What is cholestasis?
Obstructive jaundice, liver obstruction
What are the 3 types of cholestasis?
1) Pre-hepatic
2) Hepatic
3) Post-hepatic
Which LFTs rise in cholestasis?
AP and GGT
What are the 3 types of biliary disorders (affect bile ducts)?
1) Large duct obstruction (extra hepatic biliary disorder)
2) Primary sclerosing cholangitis (large and/or small biliary disorder)
3) Primary biliary cholangitis (small interlobular biliary disorder)
What are common causes of abnormal liver enzymes/cirrhosis?
- Alcohol
- Medications
- NAFLD incl. NASH
- Space occupying lesion
- Chronic Hep B/C
- Haemochromatosis
What do you have to do for every patient with abnormal LFTs?
Investigate
What are rarer causes of abnormal liver enzymes/cirrhosis?
- Autoimmune hepatitis
- Primary biliary cholangitis
- Primary sclerosing cholangitis
- Alpha 1 antitrypsin deficiency
- Wilson’s disease
- Coeliac disease
- Sero-negative arthritis
What investigations do you do for someone with abnormal LFTs?
- FBC
- INR
- U&E
- Lipids
- Imaging - US and dopplers
- Immunology
- Virology (HBsAg, Hep C AB)
- Chemistry - ferritin, copper/caeruloplasmin
What immunology tests do you do for someone with abnormal LFTs?
- Autoantibodies - ANAs, smooth muscle antibodies, anti-mitochondrial antibodies, anti-endomyseal antibodies
- Immunoglobulins
What is normal ALT?
50 IU/L
What is haemochromatosis?
Autosomal recessive disorder that leads to iron overload (HFE gene)
When do you want to diagnose haemochromatosis before?
Before ferritin is 1000 and before organ failure
What are clinical features of haemochromatosis?
- Cirrhosis
- Skin pigmentation
- Diabetes
- Cardiomyopathy
- Arthritis
- Pituitary failure
- Hepatomegaly
How do you diagnose haemochromatosis?
- Screen for haemochromatosis with transferrin saturation
- Abnormal LFTs - high ALT
- Raised ferritin (> 200 female, > 300 male)
- HFE genotype for mutation
- Liver biopsy
- Hepatic iron estimation
- Hepatic iron index > 1.9
What condition is haemochromatosis difficult to differentiate between?
Alcoholic haemosiderosis (alcoholic iron overload) - use HII to differentiate
What is primary biliary cholangitis
- Autoimmune disease of the liver
- It results from a slow, progressive destruction of the small bile ducts of the liver, causing bile and other toxins to build up in the liver (cholestasis)
What is the typical primary biliary cholangitis patient?
Middle aged female
Why is primary biliary cholangitis no longer called primary biliary cirrhosis?
Because not everyone is cirrhotic
What are two symptoms of primary biliary cholangitis?
Itching and tiredness
How do you diagnose primary biliary cholangitis?
- Cholestatic LFTs
- Raised IgM
- Positive anti-mitochondrial antibody
What does a liver biopsy show in primary biliary cholangitis?
- Bile duct damage
- Granulomatous cholangitis
What is the treatment for primary biliary cholangitis?
Ursodeoxycholic acid, obeticholic acid
What cirrhotic changes can be seen in primary biliary cholangitis?
- Portal tract expansion with radiating septa
- Absence of bile duct (ductopenia)
- Biliary interface activity with characteristic ‘halo’
- Cirrhosis with portal-portal pattern of bridging fibrous septa
- Site previously occupied by bile duct
How do you diagnose autoimmune hepatitis?
- Raised IgG
- Positive ANA
- Positive smooth muscle antibody
- Positive liver-kidney microsomal antibody
- Liver biopsy - interface hepatitis, plasma cell infiltrates
What is the treatment for autoimmune hepatitis?
Prednisolone, azathioprine
Which gender is more likely to get primary sclerosing cholangitis?
Males
What disease is primary sclerosing cholangitis associated with?
75% association with IBD
How do you diagnose primary sclerosing cholangitis?
- Liver biopsy (onion skin fibrosis)
- ERCP (endoscopic retrograde cholangiopancreatography)/MRCP
What would you see on a liver biopsy of primary sclerosing cholangitis?
- Periductal fibrosis and epithelial atrophy in small bile ducts
- Small bile ducts replaced by fibrous cords
- Ulcers on large bile ducts
What disease is alpha 1 antitrypsin deficiency associated with?
COPD
How is alpha 1 antitrypsin deficiency diagnosed?
- Alpha antitrypsin level < 25%
- Alpha antitrypsin phenotype
- Liver biopsy - PAS positive globules
Describe Wilson’s disease
- Autosomal recessive
- Disorder of copper metabolism - caeruloplasmin synthesis defective, reduced biliary copper excretion
- Young adults/children
What are clinical features of Wilson’s disease?
- Liver cirrhosis
- Acute liver failure
- Neuropsychiatric disorders
- Kayser-Fleischer rings
How do you diagnose Wilson’s disease?
- Low serum caeruloplasmin
- Reduced serum copper
- High urinary copper excretion
- Kayser-Fleischer rings
- Liver biopsy - liver copper > 250 ug/g liver dry weight
How do you treat Wilson’s disease?
Penicillamine, transplantation
What disease would you suspect in an obese patient with abnormal AST/ALT and GGT
Non-alcoholic fatty liver disease
What imaging would you do in someone with suspected NAFLD and what would it show?
Ultrasound - echogenic liver consistent with fatty liver
What would a liver biopsy show in NAFLD?
Evidence of steatohepatitis
What is the most common cause of liver disease?
NAFLD (steatosis of liver)
What is NAFLD associated with?
- Obesity
- Cardiovascular disease
- Diabetes
What is the more serious type of NAFLD?
Non-alcoholic steatohepatitis (NASH)
What can 20% of NASH patients develop?
Cirrhosis
What can 40% of cirrhosis patients develop?
Liver failure
Why might you not biopsy someone with NAFLD to test for NASH?
- Risks of biopsy
- No proven therapy for NASH
- There are accurate non invasive markers of cirrhosis
- Can’t biopsy everyone with NAFLD
- There is the potential for sampling error in liver biopsies
Why might you want to biopsy someone with NAFLD to test for NASH?
- No other way to differentiate
- Diagnosis of NASH important prognostically
- Cirrhotic patients need to be screened for hepatocellular carcinoma
- Future therapies will be available
What are non-invasive markers of cirrhosis?
1) Physical - tissue elastography e.g. fibroscan (v accurate)
2) Biochemical - enhanced liver fibrosis score (ELF), FIB-4, NAFLD fibrosis score, fibrotest, AST:platelet (APRI)
3) Diagnosis of cirrhosis by transient elastography - ultrasonographic technique to measure tissue elasticity
What are non-invasive markers of fibrosis in NAFLD (accurate)?
- Identify severe fibrosis/cirrhosis (F3/F4)
- FIB-4
- BARD score - BMI > 30, AST/ALT > 0.8, diabetes, cut-off
- AST/ALT ratio > 0.8
What should you do if a patient is jaundiced?
Refer urgently for US scan
