• Consider liver failure in all patients with both
• abnormal liver enzymes and raised bilirubin and coagulopathy 
• whose conscious level deteriorates

Symptoms and signs

• Jaundice
• Evidence of coagulopathy (e.g. bruising, petechiae)
• Flapping tremor
• Ascites and peripheral oedema
• Malaise, nausea, vomiting
• Altered conscious level (hepatic encephalopathy)

Investigations

• FBC, INR, Fibrinogen
• U&E
• Bone profile and magnesium
• Blood glucose
• LFT (including AST and GGT)
• ABG

Acute hepatitis e.g. ALT >400

• Hepatitis E IgM, Hepatitis A IgM, Hepatitis B surface Ag and Hepatitis B core IgM
• if virology negative, EBV and CMV serology
• Even if there is no evidence of paracetamol overdose, check paracetamol level
• Liver antibodies
• SMA, ANA, AMA, LKM (liver-kidney-microsome) and ANCA

Acute on chronic liver failure

• HCVAb, HBV markers
• Liver antibodies
• SMA, ANA, AMA, LKM (liver-kidney-microsome) and ANCA
• Blood cultures (mandatory)
• including in decompensated alcohol related liver
• Ascitic fluid culture and white cell count (mandatory)
• Urine cultures
• ABG (on air)
• Chest X-ray

Table 1: Grading of encephalopathy

Look for evidence of multiple organ failure

• Patient looks severely ill/exhausted/obtunded
• Hypotension (mean arterial pressure <60 mmHg)
• despite initial fluid administration +/- inotrope dependency
• Oliguria/anuria
• Spontaneous bruising and/or mucosal bleeding
• Cerebral oedema
• evidence: bradycardia, hypertension, dilated pupils or decerebrate posturing
• Impaired gas transfer
• hypoxaemia (PaO₂ <10 kPa) despite 40% oxygen
• Metabolic acidosis
• Hypoglycaemia
• Radiological pulmonary shadowing/oedema

Look for decompensated cirrhosis

Definition

• Patients with known or suspected cirrhosis with an acute deterioration in liver enzymes and synthetic function with:
• jaundice
• increasing ascites
• hepatic encephalopathy
• renal impairment
• GI bleeding

Action

• Decompensated cirrhosis is a medical emergency
• Commence Decompensated Cirrhosis Care Bundle within first 6 hr of admission

Admission

• Admit to Liver ward or critical care
• Inform a senior member of on-call medical team (SpR or above)
• After patient review, contact on-call gastroenterologist for urgent assistance
• where appropriate discuss with regional liver transplant unit

Indications for consideration of transfer to critical care

• Other organ failure in patients with acute liver failure
• e.g. respiratory failure and cardiovascular instability
• Grade 3 or 4 encephalopathy
• Features of cerebral oedema

Fluid management

Hyperglycaemia

• Correct intravascular fluid depletion with 500 mL Hartmann’s over 1 hr, repeating until MAP >65 mmHG and lactate <2 mmol/L
• Use regimen recommended in Control of hyperglycaemia unable to eat and drink guideline

Hypoglycaemia

• Correct intravascular fluid depletion with 500 mL Hartmann’s over 1 hr, repeating until MAP >65 mmHg and lactate <2 mmol/L
• Correct hypoglycaemia with 500 mL glucose 10% IV over 6–8 hr
• Then use regimen recommended in Control of hyperglycaemia unable to eat and drink guideline

Glucose normal

• Correct intravascular fluid depletion with 500 mL Hartmann’s over 1 hr, repeating until MAP >65 mmHg and lactate <2 mmol/L
• Give maintenance crystalloid 3 L/day to maintain serum Na⁺ >130 mmol/L
• give pre-mixed bags of sodium chloride 0.9% with 20 or 40 mmol/L potassium chloride to maintain serum K⁺ >3.5 mmol/L

Hypophosphataemia

• Correct with phosphate polyfusor (Fresenius Kabi) IV
• 500 mL bag gives 81 mmol sodium, 9.5 mmol potassium and 50 mmol phosphate
• moderate hypophosphataemia (0.5-0.7 mmol/L), treat with 0.1-0.2 mmol phosphate/kg (equivalent to 1-2 mL/kg) over 12 hr
• severe hypophosphataemia (<0.5 mmol/L), treat with 0.2-0.5 mmol phosphate/kg (equivalent to 2-5 mL/kg) over 12 hr
• total maximum dose of 50 mmol per infusion
• repeat doses may be required on subsequent days
• reduce dosage in elderly patients and those with reduced renal function

Respiratory failure

• Correct hypoxia - see Oxygen therapy in acutely hypoxaemic patients guideline

Coagulopathy

• If INR >1.4 with significant bleeding or need to perform an invasive procedure, give phytomenadione (Konakion MM) 10 mg IV daily by slow IV infusion in 55 mL glucose 5%
• If bleeding, discuss with on-call haematologist
• Do not give fresh frozen plasma unless clinical evidence of bleeding

Infection

• Treat all infections as serious as these patients exhibit few clinical signs of infection

Penicillin Allergy

• True penicillin allergy is rare
• Ask the patient and record what happened when they were given penicillin
• If any doubt about whether patient is truly allergic to penicillin, seek advice from a microbiologist or consultant in infectious diseases

Infection Control alerts

• Check for IC alert
• if IC alert not available, check previous 12 months of microbiology reports
• If MRSA present, treat as tagged for MRSA. See MRSA management
• If ESBL, MGNB, CARB present, treat as tagged for ESBL. See ESBL/MGNB/CARB management

Table 2: Choice of antimicrobials

¹ Check iPortal for IC alert under patient alerts; if CARB present then discuss with microbiologist for empirical treatment

Duration of anti-microbial treatment

• If not responding after 48 hr or further deterioration in liver or renal function, discuss with consultant microbiologist/ID
• When significantly improved and >48 hr apyrexial, consider stopping

Encephalopathy

• Consider giving Pabrinex® IV - see Alcohol withdrawal guideline
• Assess for precipitant
• If clinical doubt in a confused patient, request CT head to exclude subdural haematoma
• Except in fulminant liver failure, give lactulose 30-50 mL oral or via nasogastric (NG) tube 8-hrly, or phosphate enema rectally daily
• adjust dosage to produce 2-3 soft stools daily. It is not necessary to produce diarrhoea
• Avoid sedatives (benzodiazepines, phenothiazines, opioids)

Varices

• If evidence of upper Gl haemorrhage, refer to gastroenterology team for advice on:
• terlipressin infusion (must be used with caution in acute liver failure) and
• possible endoscopy and variceal banding. See Acute upper gastrointestinal haemorrhage guideline

Ascites

• Do not treat urgently unless it is causing symptoms
• if encephalopathic, avoid or stop diuretics even if symptomatic
• If ascites symptomatic, give spironolactone 100 mg oral daily
• increasing by 100 mg every 2-3 days if necessary (max 400 mg daily)
• aim for weight reduction of 0.5-1 kg/day
• If spironolactone not effective, furosemide 40 mg oral daily (max 40 mg, 0800 and 1200 hr) may be added
• If hyponatraemia Na <120 mmol/L or creatinine increases x 2 or above 200 micromol/L, discontinue both diuretics

Ascitic drainage

• If drainage thought necessary, stop diuretics for 48 hr around period of paracentesis
• Replace fluid volume drained with IV infusions of albumin 
  
  • at outset, albumin 20% 100 mL IV over 1 hr
  • in patients with risk factors for renal dysfunction or previous episodes of AKI, repeat for every 2 L of ascites drained 
  • in other patients, repeat for every 3 L of fluid drained

Spontaneous bacterial peritonitis [non Continous Ambulatory Peritoneal Dialysis (CAPD)]

• If condition deteriorates or there is evidence of sepsis, exclude SBP
  • if delay in treatment, carries a high mortality
  • arrange urgent ascitic tap for MC&S and ascitic fluid WCC
• If SBP confirmed (ascitic PMN >250 x 10⁶/L)
  • give albumin 1.5 g/kg IV over 6 hr and 1 g/kg on day 3 over 6 hr
  • start antimicrobials and antifungals
• Check ascetic fluid WCC/PMN count on day to confirm response to treatment

Table 3: Choice of anti-microbials

¹Check iPortal for IC alert under patient alerts: if ESBL present then treat as tagged for ESBL; if CARB present then discuss with microbiologist for empirical treatment

Duration of anti-microbial treatment

• If not responding after 48 hr or further deterioration in liver or renal function, discuss with consultant microbiologist/ID
• With clinical improvement, switch to oral antimicrobials (total duration 5-10 days)
• When significantly improved and >48 hr apyrexial, consider stopping
• At end of course, in cirrhotic patients only after first confirmed episode of SBP, start prophylactic ciprofloxacin 500 mg oral once daily or co-trimoxazole 960 mg once daily on discharge
• continue until ascites resolved

AKI and/or hyponatraemia (Na <125 mmol/L)

• If patient develops hyponatraemia (<125 mmol/L) or doubling of serum creatinine, stop diuretics
• only if no renal impairment, restrict fluid and salt intake

AKI defined by Rifle criteria

• Increase in serum creatinine ≥26μmol/L within 48 hr or
• ≥50% rise in serum creatinine over the last 7 days or
• Urine output (UO) <0.5 mL/kg/hr for more than 6 hr based on dry weight or
• Clinically dehydrated

Treatment

• Suspend all diuretics and nephrotoxic drugs
• Fluid resuscitate with human albumin solution 4.5% or sodium chloride 0.9%
• 250 mL boluses with regular reassessment: 1-2 L will correct most losses
• Initiate fluid balance chart/daily weights
• Aim for MAP >65 mmHg to achieve UO >0.5 mL/kg/hr based on dry weight
• At 6 hr, if target not achieved or NEWS worsening, consider escalation to higher level of care

Cerebral oedema

• Refer to critical care and with their support
• Disturb as little as possible and nurse at 15-30 degrees head up
• Treat seizures. See Status epilepticus guideline
• Avoid terlipressin
• Aim to maintain serum Na⁺ >140 mmol/L with sodium chloride 1.8% by IV infusion
• For acute episodes, give mannitol 20% (200 g in 1 L) 0.25-2 g/kg by IV infusion (use 15-30 micron in-line filter) through large peripheral or central vein over 30-60 min
  • if urine output and/or serum osmolality fail to rise or vital signs deteriorate, repeat 1-2 times after 4-8 hr
• Maintain pCO₂ 4.5-5.0 kPa and pO₂ >9 kPa

In-day

• Pulse oximetry continuously
• Urine output hourly
• Blood glucose 2-hrly
• BP 4-hrly
• Pulse 4-hrly
• Temperature 4-hrly
• Conscious level 4-hrly

Daily

• If following paracetamol overdose, twice daily
• FBC, INR
• U&E, lactate
• Weight and fluid balance

Alternate days

• LFT, bone profile and magnesium

• Discharge when recovered
• Discuss need for follow-up with gastroenterology team