Acute liver failure

Question 1

what does the liver do?

Answer 1

• protein synthesis - a’a’, albumin, CRP, complement
• hormone synthesis - IGR (growth), thrombopoietin, angiotensinogen
• clotting factors/proteins - prothrombin, fibrinogen
• plasma protein carriers - transferrin (Fe), (A-)
• bilirubin conjugation
• bile production - acids (emulsify fats), pigments (haem excretion)
• metabolism of a’a’ to NH3 (then to urea, excreted in urine)
• carbohydrate metabolism

Question 2

define ALF (acute liver failure)?

Answer 2

• INR >1.5 (coagulopathy)
\+
• encephalopathy
\+
• no known liver disease (otherwise, it is "decompensated")

Question 3

how much of the liver has to be damaged before ALF?

Answer 3

2/3

Question 4

which time scale of ALF has best prognosis?

Answer 4

hyperacute (<1 week)

Question 5

causes of ALF?

Answer 5

• paracetamol
• alcohol
• viral (B, C, CMV, etc)
• no cause/seronegative
• drugs (phenytoin, valproate, isoniazid etc)
• metabolic (Wilson’s, Reye’s, haemachrom., a-1 anti-trypsin def)
• vascular (ischaemic, Budd-Chiari)
• pregnancy (HELLP, FLoP)
• AI (PBC, PSC, AI hep)
• fatty liver disease
• CA

Question 6

commonest UK cause of ALF?

Answer 6

paracetamol

Question 7

commonest global cause of ALF?

Answer 7

viral

Question 8

atypical viral causes of ALF?

Answer 8

• HSV
• CMV
• EBV

Question 9

Hx: patient comes in with vague feelings of tiredness, anorexia, N, weight loss?

Ex: jaundiced, with fetor hepaticus, encephalopathy, asterixis/flap and abdo/RUQ pain?

Answer 9

ALF

Question 10

Ix ALF?

Answer 10

BEDSIDE:
• Urine dip (culture, AKI?, 24hr copper)
• Pregnancy test

BLOODS:
• **early sign = ↑↑ PT/INR, ↓ synthetic function also means ↓A-, ↓ glucose
• ↓ LFT
• FBC (infection ↑wbc, haemolytic anaemia and ↓Hb in Wilson’s)
• ABG (acidosis due to lactate clearance)
• U+E (AKI)
• blood culture
+/-
• paracetamol levels
• viral serology
• auto-Ab
• ceruloplasmin and 24hr urine copper (Wilson’s)
• ferritin
• a-1 antitrypsin
• B-hCG

IMAGING:
• abdo US + doppler (hepato/splenomegaly, cirrhosis, hepatic vein thrombosis)
• CXR (rule out aspiration pneumonia in ↓ LOC)

SPECIAL:
• ascitic tap for MC+S of ascites (***neutrophils >250 = SBP)

Question 11

Ix: what hepatic auto-Ab are there?

Answer 11

• ANA
• ASMA
• AMA
• ANCA

Question 12

what is hepatorenal syndrome, and how does it come about?

Answer 12

cirrhosis + ascites + renal failure

mechanism
• liver cells damaged and release NO
• NO is a vasodilator and ↓BP
• heart tries to ↑CO
• but ↓BP leads to ↓ renal perfusion
• kidney kicks off about this by activating RAS pathway
• this increases Na+ and H2O retention (ASCITES**)
• vasoconstriction of efferent renal vessels therefore kidney damage

Question 13

complications of ALF?

Answer 13

• cerebral oedema (↑ICP leads to brain hypoperfusion +/- coning)
• sepsis/shock
• AKI

Question 14

commonest cause of death in ALF?

Answer 14

cerebral oedema

Question 15

what causes hepatic encephalopathy?

Answer 15

• less NH3 cleared
• crosses BBB and converted into glutamine
• increases intracellular pressure and fluid shift leads to cerebral oedema

Question 16

how is hepatic encephalopathy graded?

Answer 16

1-4

1. mildly altered mental status, dyspraxia
2. asterixis and lethargy, slurring, inappropriate
3. UMN signs, disorientated and incoherent, sleepiness
4. coma

Question 17

how to Tx hepatic encephalopathy?

Answer 17

• lactulose +/- phosphate enemas

* rifaximin to kill gut bacteria (bacteria produce NH3)

Question 18

what is constructional apraxia?

Answer 18

Ex finding in encephalopathy

e.g cannot copy a 5 pointed star

Question 19

Hx: hypercoagulable pt presents with abdo pain, hepatomegaly, ascites, and raised transaminases?

Answer 19

Budd-Chiari syndrome
• hepatic vein thrombosis/CA causing obstruction
• congestive ischaemia
• hepatocyte damage

Ix
• US + doppler
• cause? (COCP, pregn, CA, polycythaemia, thrombophilia, TB, liver, renal tumour)

Tx
• anticoagulate
• TIPS (transjugular intrahepatic portsystemic shunt)

Question 20

Tx ALF?

Answer 20

conservative
• nurse with 20 degree head up tilt
• intubate, NG, catheterise, CVC
• monitor: obs, daily weight, bloods
• nutrition - thiamine and folate

medical
• 10 percent glucose IV 1 litre/12 hours
• Tx cause!
• phenytoin (seizures)
• RRT if renal failure

surgical
• transplant

Question 21

how to Tx complications of ALF:
• cerebral oedema?
• ascites?
• bleeding?
• Abx?
• hypogl?
• encephalopathy?

Answer 21

• mannitol IV 20 percent
• low fluid/Na+ diet, diuretics
• Vit K 10mg/day, plts, FFP + blood
• ceftriaxone
• as per normal hypo
• avoid sedatives, nurse at 20 degrees, lactulose, rifaximin

Question 22

drugs to avoid in ALF?

Answer 22

• hepatotoxic drugs
• constipating drugs (encephalopathy risk)
• oral hypo
• Na+ IVT

Question 23

ΔΔ to consider in hepatic encephalopathy?

Answer 23

• hypoglycaemia
• sepsis
• trauma
• postictal

Question 24

king’s college criteria for liver transplant in ALF due to paracetamol?

Answer 24

• pH <7.3 24hrs after ingestion of paracetamol
OR ALL THREE:
• PT>100
• creatinine >300
• grade 3/4 encephalopathy

Question 25

king's college criteria for liver transplant in ALF due to NON-paracetamol?

Answer 25

• PT>300 ``` OR 3/5: • drug induced • age <10, >40 • >1wk from 1st jaundice to encephalopathy • PT >50s • bilirubin >300 ```