Key facts:
Authors: Natalie Acors and Andrew Stein
Top Tip: ALF can be very rapid; seek senior help early
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
Background
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
- Paracetamol
- Viral hepatitis
- Other drugs or toxins (eg ecstasy, halothane, herbs, mushrooms)
- Rare causes include Budd-Chiari syndrome, auto-immune hepatitis, Wilson’s disease, acute fatty liver of pregnancy or Reye’s syndrome
[Ref]
Precipitants of ALF (in compensated chronic liver disease)
- 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 (NB: exclude hypoglycaemia in this setting)
- The presence of ascites suggests acute decompensation of chronic liver disease. Management of this discussed elsewhere
Investigation
LFTs do not reflect function, rather damage. This is why hepatologists call them 'liver enzymes'
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
Note 1: 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
Note 2: 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
Even though the underlying damage to the liver is not treatable, there are things you can do
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):
- 150 mg/kg in 200 ml 5% Dextrose over 15 min
- Then 50 mg/kg in 500 ml 5% Dextrose over 4 hours
- Then 100 mg/kg in 1L 5% Dextrose over 16 hours
- 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
Treatment (second line)
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
Prescribing issues
- Avoid sedative drugs; prescribing in ALF is difficult - ring an expert
Admit?
- Yes
Bed plan
- Medical admission ward
- ± Hepatology
- ± ITU
Referrals
Medical
- Hepatology
- ± ITU
- ± Psychiatry
- ± Liver transplant unit
The Rest
Ring the liver transplant centre, whatever the alcohol history. Denying the patient a transplant is not your decision
Complications
- Cerebral oedema
- Multi-organ failure
Prognosis
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!
Red flags
- INR >1.3 and rising
- Reduced conscious level, or agitation
- Hypoglycaemia
