GI - Liver failure

Question 1

(7) Key Functions of the Liver

Answer 1

• Synthesis of clotting factors (except factor 8)
• Glucose homeostasis-gluconeogenesis, glycogen storage
• Albumin synthesis
• Conjugation and clearance of bilirubin
• NH3 metabolism- the urea cycle
• Drug metabolism and clearance
• Immune - dealing with gut derived bacteria and bacterial products

Question 2

What (3) can you check for routine liver function tests?

Answer 2

• bilirubin
• albumin
• clotting profile

Question 3

Which clotting profile tells you more about liver disease?

Answer 3

INR affected more by liver disease than APTT

Question 4

Why may cholestasis lead to higher INR?

Answer 4

Due to poor absorption of fat soluble vitamins including vitamin K -> vitamin K deficiency -> reduced factors 2, 7, 9, 10 -> higher INR

Question 5

45yo female, 7 wks post total abdominal hysterectomy
•Increasing abdominal pain over 2 days
•Vomiting
•No bowel actions
•Anorexia
•Weight loss (10kg over last 7 weeks)
taking Paracetamol PRN, Mylanta PRN

Soft non-tender, distended abdomen

AXR - incomplete mid to distal small bowel obstruction

Dx?

Answer 5

Recurrent subacute bowel obstruction secondary to adhesions from previous TAH

Question 6

Initial Mx of bowel obstruction

Answer 6

–Nasogastric tube
–Intravenous therapy and electrolyte replacement
–NBM
–Analgesia (paracetamol 1g QID strict)

Question 7

(4) common causes of acute liver injury

Answer 7

• Drug poisoning: paracetamol
• Acute viral hepatitis: hepatitis A, hepatitis B, hepatitis C. Less common EBV, others
• Idiosyncratic acute drug reactions
• Ischaemia: Circulatory shock, acute severe heart failure

Question 8

Ix for acute liver injury

Answer 8

• paracetamol in blood
• HCV Ab
• IgM anti-HAV, IgG anti-HAV
• HBsAg, HBcAg, HBsAb
• Liver ultrasound

Question 9

What do HBsAg, HBcAg, HBsAb tell you?

Answer 9

HBsAg: RECENT infection or vaccination

HBcAg: previous/current INFECTION ONLY with HepB

HBsAb: previous/current infection OR vaccination

Question 10

What (7) are the common causes of acute hepatitis ?

Answer 10

1) Acute viral hepatitis
2) Drug related
3) Ischaemic hepatitis
4) Autoimmune
5) Acute Budd Chiari
6) Wilson’s disease
7) idiopathic

Question 11

When (3 criteria) do you transfer patient to a liver transplant unit due to acute liver injury?

Answer 11

–INR > 1.5 and rising (except POD)
–Any encephalopathy
–Poor prognosis

Question 12

What may Ingestion of 10 or more standard paracetamol tablets result in?

Answer 12

fulminant hepatic failure resulting in death within 5-7 days if unchecked

Question 13

Define acute liver failure

Answer 13

• Rapid deterioration of liver function in previously normal liver
• Trey and Davidson 1970 : “jaundice to encephalopathy within 1.5, any encephalopathy, duration of illness (jaundice) up to 26 weeks

Question 14

Intervention for paracetamol acute liver failure

• when is it effective
• mechanism

Answer 14

NAC (N-acetylcysteine)

100% effective if given within 8 hours of ingestion, regardless of dose ingested

–Acts as glutathione donor
–Reduces production of toxic metabolite (NAPQI)

Question 15

Intervention for hep B acute liver failure

Answer 15

Antivirals

Question 16

Intervention for Wilson’s acute liver failure

Answer 16

Chelation/Exchange

Question 17

Intervention for Budd Chiari acute liver failure

Answer 17

TIPS (transjugular intrahepatic portosystemic shunts)

I.e. shunt connecting hepatic vein with portal vein to allow portosystemic communication

Question 18

What is Budd Chiari syndrome? What is the classical triad of symptoms

Answer 18

a condition caused by occlusion of the hepatic veins (e.g. clot) that drain the liver.

Classical triad Px:

• abdominal pain
• ascites
• liver enlargement.

Question 19

Describe primary & secondary Budd-Chiari syndrome and their common causes

Answer 19

Primary Budd–Chiari syndrome (75%): thrombosis of the hepatic vein

Related with:

1. Polycythemia vera
2. Pregnancy
3. Postpartum state
4. OCP
5. Paroxysmal nocturnal haemoglobinuria
6. Hepatocellular carcinoma
7. Lupus anticoagulants

Secondary Budd–Chiari syndrome (25%): compression of the hepatic vein by an outside structure (e.g. a tumor)

Question 20

Intervention for Autoimmune acute liver failure

Answer 20

Steroids

Question 21

(3) roles for liver biopsy in acute liver failure

Answer 21

• Quantify extent of liver injury
• Establish aetiology
• Guide to treatment

Question 22

What criteria do you use to choose patients for liver transplantation?

Answer 22

King’s college criteria

For identifying patients with poor prognosis who need transplantation

Question 23

What is the toxic dose of paracetamol?

• 24 hours
• 48 hours
• > 48 hours

Answer 23

• 24 hours – 200mg/kg or 10g - whichever is less
• 48 hours – 150 mg/kg or 6g per day – whichever is less
• > 48 hours – 100 mg/kg or 4g per day – whichever is less

Question 24

(2) common clinical scenarios of paracetamol OD fulminant hepatic failure

Answer 24

1. Prolonged courses in fasting individuals: therapeutic doses
2. Supra-therapeutic doses in alcoholics & often in short courses

Question 25

How does paracetamol metabolism occur in the liver?

Answer 25

95% of paracetamol is bound by glucuronide & excreted in bile 5% are metabolised by P450 to NAPQI. Some of them are conjugated with glutathione & hence non toxic. But when both glucuronide & glutathione are used up, the unconjugated NAPQI cause hepatotoxicity.

Question 26

General Mx for paracetamol OD acute liver injury - prevention of absorption - symptomatic care - risk assessment - specific care

Answer 26

•Prevention of absorption –Activated charcoal within 60 minutes of ingestion •Symptomatic care –Anti-emetics •Risk assessment –Dose based / plasma paracetamol concentration •Specific care –N-acetylcysteine

Question 27

Describe the use of activated charcoal & its SE

Answer 27

Used to treat poisonings and overdoses following oral ingestion. - not effective for a number of poisonings including strong acids or alkali, cyanide, iron, lithium, arsenic, methanol, ethanol or ethylene glycol - over-the-counter drug to treat diarrhea, indigestion, and flatulence. SE: - pulmonary aspiration which can sometimes be fatal if immediate medical treatment is not initiated. - contraindicated when the ingested substance is an acid, an alkali, or a petroleum product.

Question 28

Describe the Mx of paracetamol OD for: | - 8 hours

Answer 28

measure serum paracetamol level 1-8hours: - measure serum paracetamol level -> plot serum paracetamol level on nomogram, if over nomogram treatment line -> NAC infusion >8 hours: - commence NAC infusion -> measure serum paracetamol level & ALT. Plot serum paracetamol level on nomogram, if over nomogram treatment line, continue NAC infusion till normalised ALT.

Question 29

Causes of chronic liver disease (the rule of 3/s)

Answer 29

* Most common: Alcohol, HBV, HCV * Genetic: Wilson’s disease, Haemochromatosis, A1AT deficiency * Auto-immune: Primary biliary cirrhosis, primary sclerosing cholangitis, Autoimmune hepatitis * Other: NASH, drugs, budd chiari syndrome

Question 30

(3) genetic causes of chronic liver disease

Answer 30

- Wilson’s disease - Haemochromatosis - A1AT deficiency

Question 31

(3) autoimmune causes of chronic liver disease

Answer 31

- Primary biliary cirrhosis - primary sclerosing cholangitis - Autoimmune hepatitis

Question 32

(3) most common causes of chronic liver disease

Answer 32

Alcohol, HBV, HCV

Question 33

Ix for chronic liver disease to define the aetiology

Answer 33

- HCV Ab - HBsAg, HBcAb, HBsAb - Caeruloplasmin (low in Wilson's disease) - A1AT - Fe studies (haemochromatosis) - ANA, SMA, AMA (autoimmune)

Question 34

(3) Cx of chronic liver failure & hence preventive Mx

Answer 34

* Hepatoma (patient needs screening) * Variceal bleeding (patient needs screening) * Ascites (needs prophylacic antibiotics)