Conditions Affecting LFTs Flashcards

1
Q

What are the LFTs?

A
  • Bilirubin (BR)
  • Alkaline phosphatase (AP)
  • Alanine transaminase (ALT)
  • Aspartate transaminase (AST)
  • Gamma GT (GGT)
  • Albumin
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2
Q

Which LFTs rise in hepatitis?

A

ALT and AST

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3
Q

What is cholestasis?

A

Obstructive jaundice, liver obstruction

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4
Q

What are the 3 types of cholestasis?

A

1) Pre-hepatic
2) Hepatic
3) Post-hepatic

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5
Q

Which LFTs rise in cholestasis?

A

AP and GGT

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6
Q

What are the 3 types of biliary disorders (affect bile ducts)?

A

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)

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7
Q

What are common causes of abnormal liver enzymes/cirrhosis?

A
  • Alcohol
  • Medications
  • NAFLD incl. NASH
  • Space occupying lesion
  • Chronic Hep B/C
  • Haemochromatosis
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8
Q

What do you have to do for every patient with abnormal LFTs?

A

Investigate

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9
Q

What are rarer causes of abnormal liver enzymes/cirrhosis?

A
  • Autoimmune hepatitis
  • Primary biliary cholangitis
  • Primary sclerosing cholangitis
  • Alpha 1 antitrypsin deficiency
  • Wilson’s disease
  • Coeliac disease
  • Sero-negative arthritis
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10
Q

What investigations do you do for someone with abnormal LFTs?

A
  • FBC
  • INR
  • U&E
  • Lipids
  • Imaging - US and dopplers
  • Immunology
  • Virology (HBsAg, Hep C AB)
  • Chemistry - ferritin, copper/caeruloplasmin
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11
Q

What immunology tests do you do for someone with abnormal LFTs?

A
  • Autoantibodies - ANAs, smooth muscle antibodies, anti-mitochondrial antibodies, anti-endomyseal antibodies
  • Immunoglobulins
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12
Q

What is normal ALT?

A

50 IU/L

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13
Q

What is haemochromatosis?

A

Autosomal recessive disorder that leads to iron overload (HFE gene)

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14
Q

When do you want to diagnose haemochromatosis before?

A

Before ferritin is 1000 and before organ failure

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15
Q

What are clinical features of haemochromatosis?

A
  • Cirrhosis
  • Skin pigmentation
  • Diabetes
  • Cardiomyopathy
  • Arthritis
  • Pituitary failure
  • Hepatomegaly
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16
Q

How do you diagnose haemochromatosis?

A
  • 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
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17
Q

What condition is haemochromatosis difficult to differentiate between?

A

Alcoholic haemosiderosis (alcoholic iron overload) - use HII to differentiate

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18
Q

What is primary biliary cholangitis

A
  • 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)
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19
Q

What is the typical primary biliary cholangitis patient?

A

Middle aged female

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20
Q

Why is primary biliary cholangitis no longer called primary biliary cirrhosis?

A

Because not everyone is cirrhotic

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21
Q

What are two symptoms of primary biliary cholangitis?

A

Itching and tiredness

22
Q

How do you diagnose primary biliary cholangitis?

A
  • Cholestatic LFTs
  • Raised IgM
  • Positive anti-mitochondrial antibody
23
Q

What does a liver biopsy show in primary biliary cholangitis?

A
  • Bile duct damage

- Granulomatous cholangitis

24
Q

What is the treatment for primary biliary cholangitis?

A

Ursodeoxycholic acid, obeticholic acid

25
Q

What cirrhotic changes can be seen in primary biliary cholangitis?

A
  • 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
26
Q

How do you diagnose autoimmune hepatitis?

A
  • Raised IgG
  • Positive ANA
  • Positive smooth muscle antibody
  • Positive liver-kidney microsomal antibody
  • Liver biopsy - interface hepatitis, plasma cell infiltrates
27
Q

What is the treatment for autoimmune hepatitis?

A

Prednisolone, azathioprine

28
Q

Which gender is more likely to get primary sclerosing cholangitis?

A

Males

29
Q

What disease is primary sclerosing cholangitis associated with?

A

75% association with IBD

30
Q

How do you diagnose primary sclerosing cholangitis?

A
  • Liver biopsy (onion skin fibrosis)

- ERCP (endoscopic retrograde cholangiopancreatography)/MRCP

31
Q

What would you see on a liver biopsy of primary sclerosing cholangitis?

A
  • Periductal fibrosis and epithelial atrophy in small bile ducts
  • Small bile ducts replaced by fibrous cords
  • Ulcers on large bile ducts
32
Q

What disease is alpha 1 antitrypsin deficiency associated with?

A

COPD

33
Q

How is alpha 1 antitrypsin deficiency diagnosed?

A
  • Alpha antitrypsin level < 25%
  • Alpha antitrypsin phenotype
  • Liver biopsy - PAS positive globules
34
Q

Describe Wilson’s disease

A
  • Autosomal recessive
  • Disorder of copper metabolism - caeruloplasmin synthesis defective, reduced biliary copper excretion
  • Young adults/children
35
Q

What are clinical features of Wilson’s disease?

A
  • Liver cirrhosis
  • Acute liver failure
  • Neuropsychiatric disorders
  • Kayser-Fleischer rings
36
Q

How do you diagnose Wilson’s disease?

A
  • Low serum caeruloplasmin
  • Reduced serum copper
  • High urinary copper excretion
  • Kayser-Fleischer rings
  • Liver biopsy - liver copper > 250 ug/g liver dry weight
37
Q

How do you treat Wilson’s disease?

A

Penicillamine, transplantation

38
Q

What disease would you suspect in an obese patient with abnormal AST/ALT and GGT

A

Non-alcoholic fatty liver disease

39
Q

What imaging would you do in someone with suspected NAFLD and what would it show?

A

Ultrasound - echogenic liver consistent with fatty liver

40
Q

What would a liver biopsy show in NAFLD?

A

Evidence of steatohepatitis

41
Q

What is the most common cause of liver disease?

A

NAFLD (steatosis of liver)

42
Q

What is NAFLD associated with?

A
  • Obesity
  • Cardiovascular disease
  • Diabetes
43
Q

What is the more serious type of NAFLD?

A

Non-alcoholic steatohepatitis (NASH)

44
Q

What can 20% of NASH patients develop?

A

Cirrhosis

45
Q

What can 40% of cirrhosis patients develop?

A

Liver failure

46
Q

Why might you not biopsy someone with NAFLD to test for NASH?

A
  • 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
47
Q

Why might you want to biopsy someone with NAFLD to test for NASH?

A
  • No other way to differentiate
  • Diagnosis of NASH important prognostically
  • Cirrhotic patients need to be screened for hepatocellular carcinoma
  • Future therapies will be available
48
Q

What are non-invasive markers of cirrhosis?

A

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

49
Q

What are non-invasive markers of fibrosis in NAFLD (accurate)?

A
  • Identify severe fibrosis/cirrhosis (F3/F4)
  • FIB-4
  • BARD score - BMI > 30, AST/ALT > 0.8, diabetes, cut-off
  • AST/ALT ratio > 0.8
50
Q

What should you do if a patient is jaundiced?

A

Refer urgently for US scan