Liver failure

Question 1

What is liver failure?

Answer 1

Liver failure = severe liver dysfunction leading to jaundice, encephalopathy and coagulopathy

Question 2

What are the classifications of liver failure?

Answer 2

Hyper-acute liver failure = jaundice with encephalopathy occurring <1 week of onset

Acute = jaundice with encephalopathy occurring 1-4 weeks of onset

Sub-acute = jaundice with encephalopathy occurring with 4-12 weeks of onset

Acute-on-chronic = acute deterioration/decompensation in patients with chronic liver disease/cirrhosis (Most often)

Fulminant hepatic failure = clinical syndrome resulting from massive necrosis of liver cells leading to severe impairment of liver function

Question 3

What is the aetiology of liver failure?

Answer 3

Viral - HepA, B, D, E, Non A-E hepatitis

Drugs - Paracetamol overdose, Idiosyncratic drug reactions

Uncommon
AI hepatitis
Budd-Chiari syndrome (vascular)
Pregnancy related malignancy (e.g. lymphoma)
Haemochromatosis
Mushroom (Amanita phalloides) poisoning
Wilson’s disease
Alpha1-antitrypsin deficiency

Decompensated alcoholic liver disease

Question 4

What are the risk factors of liver failure?

Answer 4

Viral hepatitis
Paracetamol overdose (50% of cases in UK)
Alcohol misuse

Question 5

What is the pathogenesis of liver failure?

Answer 5

Jaundice:
Decreased secretion of conjugated bilirubin

Encephalopathy:
Increased delivery of gut-derived products into the systemic circulation and brain (Due to reduced extraction of nitrogenous products)

Astrocytes in the brain use these products to convert glutamate to glutamine, and the excess glutamine causes an osmotic imbalance – resulting in cellular swelling and cerebral oedema

Coagulopathy
Reduced synthesis of clotting factors
Reduced platelets

Question 6

What are the symptoms of liver failure?

Answer 6

May be asymptomatic
Fever
Nausea

Question 7

What are the signs of liver failure?

Answer 7

Jaundice

Hepatic encephalopathy:
Grade I - Altered mood/behaviour, Sleep disturbance, Dyspraxia, Poor arithmetic, NO liver flap

Grade II - Increasing drowsiness, Confusion, Slurred speech, MAYBE liver flap, Inappropriate behaviour

Grade III - Incoherent, Restless, Liver flap, Stupor, NOT coma

Grade IV - Coma

Fetor hepaticus = pear drop smell

Asterixis/liver flap (Negative myoclonus)

Constructional apraxia

CLD stigmata – suggest acute-on-chronic (p260)

Effects of portal hypertension - Ascites, Splenomegaly, Haematemesis, Melena, Caput medusa = dilated abdominal veins , Haemorrhoids

Effects of liver-cell failure - Fetor hepaticus, Spider naevi, Gynaecomastia, Jaundice, Loss of sexual hair, Testicular atrophy, Liver flap, Bruising, Ankle oedema

Signs of secondary causes - Bronze skin colour, Kayser-Fleischer rings

Question 8

What are appropriate investigations for liver failure?

Answer 8

Identify cause - Viral serology, Paracetamol levels, Autoantibodies, Ferritin, Wilson’s (= Caeruloplasmin: Low, Urinary copper: Raised), Alpha1-antitrypsin

Bloods - FBC (Hb: Reduced if GI bleed, WCC: Raised if infection), U+Es: RF, Glucose
LFTs - Bilirubin: Raised, Transaminases and GGT: Raised, AlkPhos: Raised, Albumin: Low
ESR/CRP
Coagulation screen: Increased PT and INR

ABG + lactate

US

CT

Ascitic fluid tap - MC+S, Neutrophils >250/mm3 = SBP
Biochemistry: glucose, protein

Doppler of portal/hepatic vein - Abnormal in Budd-Chiari syndrome

EEG - Monitor encephalopathy

Question 9

What is medical management for liver failure?

Answer 9

Resuscitation - ABCDE, ITU care

Treat cause
IF paracetamol overdose - N-acetyl cysteine

Treatment
Invasive ventilatory support: Intubation

Monitor: Vital signs, PT, pH, creatinine, urine output, encephalopathy, fluid status, glucose

Infection prophylaxis - ABs: Ceftriaxone 1-2g/24hrs, Antifungals

Protect gastric mucosa against stress ulceration - PPIs: Omeprazole 40mg/d IV/PO, Sulcralfate

Maintain nutrition - Dietician input – NG feeding, Thiamine and folate supplements

IF seizures - Lorazepam (Careful with pharmacy)
Avoid hepatotoxic drugs, normally metabolised by the liver (Paracetamol, methotrexate, azathioprine, oestrogen, salicylates)
Warfarin effects are enhanced
Avoid drugs that constipate (opiates, diuretics) - Increase the risk of encephalopathy, Avoid oral hypoglycaemics, Avoid saline-containing IVIs

Complication treatment
IF renal failure - Hemofiltration, Nutritional support

IF cerebral oedema - 20% IV Mannitol (reduced increased ICP), Hyperventilate

IF ascites - Low protein diet?

IF bleeding/coagulopathy - IV VitK 10mg/d IV for 3 days, FFP, Platelet infusions if required

IF hypoglycaemia (<2 mmol/L or symptomatic), 50% glucose IV 50ml

IF encephalopathy - Nurse at 20oc, 20o head-up tilt, Lactulose (30-50mL/8hrs), Phosphate enemas, Avoid sedatives

Question 10

What is the surgical and conservative management of liver failure?

Answer 10

King’s College Hospital criteria for liver transplantation

IF paracetamol overdose : Arterial ph <7.3 OR, PT > 100s, creatinine >300 AND severe encephalopathy (III/IV)

IF other cause (3/5) - Age <10 or >40, Bilirubin > 300uM,
Caused by non-A, non-E viral hepatitis or drugs, Hyper-acute - >7 days between onset of jaundice to encephalopathy, PT > 100s

Chronic, conservative - Alcohol abstinence, Nutrition optimisation, Low salt diet, Fluid restriction

Question 11

What are the possible complications of liver failure?

Answer 11

• Infection
• Coagulopathy
• Hypoglycaemia
• Electrolyte disturbances
• Acid-base disturbances
• Hepatorenal syndrome = concurrent hepatic and renal failure (Cirrhosis, ascites and renal failure)
• Cerebral oedema
• Increased ICP
• Respiratory failure

Question 12

What is the prognosis for liver failure?

Answer 12

Depends on severity and aetiology

Worse if - Grade III-IV encephalopathy, age > 40, albumin <30g/L, increased INR, drug-induced liver failure, late-onset hepatic failure

Surgical mortality prognostic score = Childs-Pugh score