Liver

Question 1

What are the 7 key functions of the liver?

Answer 1

• Glucose homeostasis - gluconeogenesis & glycogen storage
• Synthesis of clotting factors
• Drug & toxin metabolism
• Bilirubin conjugation & clearance
• Albumin synthesis
• NH3 metabolism
• Immune functions

Question 2

If ALT > AST in an acute presentation, what 3 aetiologies should you be most suspicious of?

Answer 2

• Acute viral hepatitis
• Acute drug toxicity
• Liver ischaemia

Question 3

If LFTs show AST > ALP, what 3 aetiologies does it raise the suspicion of?

Answer 3

• Alcohol
• Cirrhosis
• Paracetamol

Question 4

What 3 parameters of the LFTs are mostly greatly affected in cholestasis?

Answer 4

Bilirubin, GGT, ALP

Question 5

What are some of the definitions of acute liver failure?

Answer 5

• Rapid deterioration of liver function in a previously normal liver
• INR >1.5 or any encephalopathy that develops in under 26 weeks
• ‘Jaundice to encephalopathy in

Question 6

Name the 4 broad causes of acute liver failure.

Answer 6

• Paracetamol toxicity
• Acute viral hepatitis
• Ischaemia
• Other drug reaction

Question 7

What intervention can improve the outcome of acute liver failure from paracetamol toxicity?

Answer 7

N-acetylcysteine

Question 8

What intervention can improve the outcome of acute liver failure from hepatitis B?

Answer 8

Anti-virals

Question 9

What intervention can improve the outcome of acute liver failure from Wilson’s disease?

Answer 9

Chelation/exchange

Question 10

What intervention can improve the outcome of acute liver failure from Budd-Chiari syndrome?

Answer 10

Shunt insertion (TIPS - transjugular intrahepatic portosystemic shunt)

Question 11

What intervention can improve the outcome of acute liver failure from acute fatty liver of pregnancy?

Answer 11

Delivery

Question 12

What intervention can improve the outcome of acute liver failure from autoimmune hepatitis?

Answer 12

Steroids

Question 13

What abnormalities would you expect on liver biopsy following paracetamol overdose?

Answer 13

• Panlobular necrosis
• Relative preservation of portal tracts
• No early inflammatory response

Question 14

Outline the pathogenesis of acute liver failure in paracetamol toxicity.

Answer 14

• Paracetamol is normally metabolized by hepatic glutathione, which conjugates it to glucuronide & excretes it in bile
• When this path is saturated, paracetamol is metabolized via the CYP450 pathway, and becomes a toxic metabolite - NAPQI
• Glutathione normally conjugates NAPQI to make it non-toxic
• When glutathione stores are depleted, the NAPQI accumulates & becomes hepatotoxic

Question 15

What is considered a toxic dose of paracetamol?

Answer 15

200mg/kg or 10g, whichever is less

Question 16

How does N-acetylcysteine work & how soon after paracetamol OD does it need to be given?

Answer 16

NAC works by acting as a glutathione donor (so paracetamol can be excreted even when hepatic glutathione stores are depleted)
-it needs to be given within 8 hours of OD to be 100% effective

Question 17

Name 4 steps in the management of acute paracetamol overdose.

Answer 17

• Reduce absorption: give activated charcoal
• Symptomatic care: anti-emetics
• Risk assessment: dose based/plasma paracetamol concentration
• Specific treatment: NAC

Question 18

Name the causes of chronic liver disease under the following headings - Big 3, Metabolic 3, Autoimmune 3, Other 3:

Answer 18

Big 3: alcohol, hepatitis B, hepatitis C
Metabolic 3: Wilson’s disease, A1AT deficiency, haemochromatosis
Autoimmune 3: Autoimmune hepatitis, Primary sclerosing cholangitis, Primary biliary cirrhosis
Other 3: fatty liver disease, Budd-Chiari, chronic biliary obstruction

Question 19

What are 5 symptoms of chronic liver disease?

Answer 19

• Fatigue
• Weight loss or gain
• Abdominal distension
• Confusion
• Bleeding

Question 20

What are 9 signs of chronic liver disease?

Answer 20

• Jaundice
• Spider naevi
• Caput medusae
• Ascites
• Encephalopathy
• Asterixis
• Clubbing
• Dupuytrens contracture
• Splenomegaly
• Leukonychia
• Palmar erythema
• Parotidomegaly (only alcohol)
• Gynaecomastia
• Bruising

Question 21

Outline the stages of liver fibrosis from F0 to F4.

Answer 21

F0 = no fibrosis
F1 = periportal fibrosis, no septa
F2 = periportal fibrosis, some periportal septa
F3 = numerous septa, no architectural distortion
F4 = architectural distorsion & nodule formation

Question 22

Name 5 major complications of CLD and how they should be managed.

Answer 22

1. Oesophageal varices - beta-blockade, band ligation, endoscopic banding
2. Fluid retention - fluid & salt restriction, diuresis
3. Jaundice - no specific treatment
4. Osteoporosis - vitamin D supplementation, regular surveillance of BMD
5. Encephalopathy - supportive care, withdraw potential precipitants

Question 23

What are 5 findings to suggest decompensated liver disease?

Answer 23

Jaundice, coagulopathy, ascites, variceal bleeding, hepatorenal syndrome

Question 24

What is the difference between type 1 and type 2 hepatorenal syndrome?

Answer 24

Type 1 is acute & a more severe renal failure

Type 2 is a more insidious renal failure that is less severe

Question 25

Name a pre-hepatic, a hepatic & a post-hepatic cause of portal hypertension.

Answer 25

Pre-hepatic: portal vein thrombosis, stenosis or compression of the hepatic blood supply Hepatic: cirrhosis, schistosomiasis, severe steatosis, sarcoidosis Post-hepatic: hepatic vein obstruction, severe RHF, constrictive pericarditis

Question 26

Outline the biopsy findings in hepatocellular carcinoma.

Answer 26

- Abnormal bile canalicular architecture - Thickened trabeculae >3 cells - Pseudo-bile duct spaces - a-fetoprotein positive

Question 27

What serum marker is usually elevated in HCC?

Answer 27

Alpha-fetoprotein

Question 28

What 2 autoantibodies are present in type 1 autoimmune hepatitis?

Answer 28

Anti-nuclear antibodies | Anti-smooth muscle antibodies

Question 29

What is primary biliary cirrhosis? Name 2 biopsy findings.

Answer 29

``` Primary biliary cirrhosis is an autoimmune disease causing non-suppurative cholangitis. Biopsy: -Florid bile duct lesions -Chronic cholestasis -Loss of small bile ducts -Variable periportal hepatitis ```

Question 30

What is the mainstay of treatment of primary biliary cirrhosis?

Answer 30

Ursodeoxycholic acid (responds poorly to steroids, unlike autoimmune hepatitis)

Question 31

Name 4 causes of hepatic granuloma & granulomatous hepatitis.

Answer 31

- Tuberculosis - Sarcoidosis - Primary biliary cirrhosis - Drugs