Acute Liver Failure

Key Differential
Diagnoses

Alcohol withdrawal syndrome
Acute hepatitis (alcohol and all other causes)
All causes liver dysfunction (incl obstruction)

Key Investigations

Paracetamol levels
Viral hepatitis serology (HAV, HBV, HEV, HSV)
FBC, U+E, LFT/GGT, Bone/phosphate
Glucose, INR
ABG/Lactate
BC
ECG, CXR
Liver/abdo US

Key Treatment

± IV VITAMIN K 10 mg, give slowly
± N-ACETYLCYSTEINE  (NAC); 150 mg/kg (in 200 ml 5% Dextrose) over 15 mins; then 50 mg/kg (in 500 ml 5% Dextrose) over 4 hours, then 100 mg/kg (in 1L 5% Dextrose) over 16h
Fluid resuscitation
Consider antibiotic/antifungal treatment

Key Management
Decisions

Liver transplant

Introduction

• ALF is the development of liver failure in a previously healthy liver
• In this situation the  INR (or prothrombin time) is the best marker of synthetic liver function
• Although 'LFTs' are sent off whenever one suspects a liver problem, the word 'function' is a misnomer. They do not reflect function, rather damage. Hepatologists call them 'liver enzymes'
• Severe elevation in liver enzymes may occur with preservation of synthetic function
• Liver failure is complicated to manage. There may be rapid deterioration over hours to multi-organ failure
• Involve hepatologists and ITU, early

Definition

Hepatic encephalopathy within 8-28 days of appearance of jaundice

Types

Pre (haemolysis), hepatic, post

Causes

Precipitants of  ALF (in chronic LF)

Excess protein in the bowel (eg GI bleed), alcohol, infection (especially gram -ve septicaemia), drugs/toxins, trauma (major and minor surgery, paracentesis), electrolyte imbalance (especially hypokalaemia, and hyponatraemia secondary to diuretics)

Risk factors

Alcohol and other enzyme inducing drugs (ie anti-epileptics) as well as  malnutrition may increase risk of paracetamol toxicity
Travel abroad
New sexual partner
Ingestion of paracetamol, any herbal remedies or toxins

Symptoms

Symptoms may be mild and non-specific until late. Nausea and vomiting common. Epigastric pain

Key question

"Have you taken any new tablets, including herbal remedies, in the last 4-6 weeks?"

Signs

May be minimal, often dehydrated
Encephalopathy (altered mood/behaviour/drowsiness/confusion/stupor/ restlessness/coma) warrants urgent attention.  Exclude hypoglycaemia
The presence of ascites suggests acute decompensation of chronic liver disease.  Management of this discussed elsewhere

Blood

FBC (Hb falling rapidly ?bleeding ?haemolysis (occurs in Wilson’s disease); low platelets
± Blood film (if low platelets)
± Reticulocytes (haemolysis?)
Clotting/INR (reversal with FFP negates its usefulness, but give vitamin K which will merely correct deficiency secondary to cholestasis)
U+E (renal failure common)
LFT/GGT
Bone/phosphate (?low), Glucose (low?), Amylase
BC
ABG (if platelets OK)
Paracetamol levels

'Liver enzymes'

• Note that even though albumin and INR are the best markers of synthetic liver function, they are not that good
• And a decrease in albumin, and rise in INR can occur late in the disease process. In other words, there is no creatinine for the liver.
• Although 'LFTs' are sent off whenever one suspects a liver problem, the word 'function' is a misnomer. They do not reflect function, rather damage. This is why hepatologists call them 'liver enzymes'

[Ref]

Other

MSU
ECG
CXR (non-cardiogenic pulmonary oedema; metastases)
Liver/abdo US
± CT head (if inappropriately drowsy for level of liver failure, consider SDH)

Key investigations

LFT, INR, U+E
ABG
Liver/abdo US - including Doppler flow studies of portal vein and hepatic veins

Specialist investigations

Acute Viral Hepatitis screen (HAV, HBcIgM (denotes acute hepatitis B), HCV, HEV, CMV, EBV, HSV);
Liver antibodies (anti-mitochondrial AB, anti-smooth muscle AB; ANA/dsDNA; Immunoglobulins;
Ferritin/Caeruloplasmin
Haptoglobin (low)/LDH (high) (haemolysis)
Urinary drug screen (ecstasy, amphetamines)
CT chest/abdomen

Differential diagnoses

Acute alcoholic hepatitis
Other causes of hepatitis, or liver dysfunction

Treatment
(first line)

Drugs
IV VITAMIN K 10 mg, slowly, for 3 days (if clotting deranged) ± FFP/Platelets
PO LACTULOSE 30 mls tds
± IV GLUCOSE, 20 mls 50%, if BG <4 mmol/L, may require continual dextrose infusion
± CO-AMOXICLAV 1.2 g tds (for ?SBP), if not previously been on prophylaxis, if already on CIPROFLOXACIN (see below) then use TAZOCIN 4.5 g tds
± IV FLUCONAZOLE 50-100 mg od for 7-14d, if encephalopathy present; as prophylaxis against fungal sepsis
± PPI
± N-ACETYLCYSTEINE (paracetamol overdose):
1. 150 mg/kg in 200 ml 5% Dextrose over 15 mins
2. Then 50 mg/kg in 500 ml 5% Dextrose over 4 hours
3. Then 100 mg/kg in 1L 5% Dextrose over 16 hours
4. Continue infusion at 100 mg/kg in 1L Dextrose over 24 hours until PT falling and INR<2. It should be noted that the evidence for all interventions for paracetamol overdose (including NAC) is weak: [Ref]
± IV PHOSPHATE (9-18 mmol/24h), if < 0.4 mmol/L; up to 50 mmol/12h on ITU
± IV MANNITOL 0.25-2g over 30-60 mins (usually 100 mls 20%), if cerebral oedema; repeated 1-2x after 4-8 hrs
Procedures
IV line; urinary catheter; likely to require aggressive fluid replacement (N Saline is appropriate); may require additional 10% dextrose to avoid hypoglycaemia

Key management decision

Consideration for liver transplant

Stop

Hepatotoxic drugs
Sedative drugs
Diuretics, if Na < 125 mmol/L

Procedures
Urinary catheter, CVP line (note platelets/clotting), arterial line (again)
Monitor intracranial pressure
Seizures – treat with IV LORAZEPAM 4mg, then repeat, if necessary (note: national shortage of lorazepam at moment; may have to use another benzodiazepine eg DIAZEPAM 10 mg over 2 mins; then repeat after 10 mins, if necessary)
Haemofiltration/haemodialysis if renal failure develops
Intubation and ventilation if Grade 3 encephalopathy
Liver transplantation

Admit?

Yes

Bed plan

Medical admission ward
± Hepatology
± ITU

Referrals

Medical
Hepatology
± ITU
± Psychiatry
Liver transplant unit

Complications

Cerebral oedema
Multi-organ failure

2° Prevention + Health Promotion 

SBP Prophylaxis - PO CIPROFLOXACIN 750mg once weekly as inpatient; 250 mg bd ongoing as outpatient
Psychiatric follow up (if due to paracetamol OD)

Don't forget

• Check all drugs (ring GP if necessary)
• To examine breasts and check the CXR
• Contact your local hepatologists or liver unit early; ring them back tomorrow too!