Acute Liver Failure

Introduction

Severe hepatic failure in which encephalopathy develops usually in under 2 weeks^p in a patient with a previously normal liver.

The syndrome was originally defined further as occurring within 8 weeks of onset of the precipitating illness, in the absence of evidence of preexisting liver disease. D

Etiology

Hyperacute (< 7 days)

Viral (Hepatitis A, B, E)

Paracetamol

Acute (8–28 days)

Cryptogenic (Non-A–E viral Hepatitis)

Drugs

Paracetamol

Halothane

Antituberculous drugs

Ecstasy

Herbal remedies

Pathophysiology

There is multiacinar necrosis involving a substantial part of the liver.

Severe fatty change is seen in pregnancy, Reye’s syndrome or following tetracycline administration intravenously.

Clinical features

Symptoms 

1. Patients may be asymptomatic or present with fatigue.
2. Features of Acute viral hepatitis (fever, nausea and vomiting & Right hypochondrial discomfort)
3. Initial clinical features are often minimal and include
1. reduced alertness
2. poor concentration,
3. progressing to restlessness and aggressive behavior  to drowsiness and coma. 

Signs

1. Jaundice (may not be present at the onset)
2. Small Liver (area of liver dullness reduced).
3. Features of cirrhosis like- hepatosplenomegaly, ascites utherwise Hepatomegaly is unusual.
4. F/O cerebral oedema
1. Unequal or abnormally reacting pupils, fixed pupils, Papilloedema occurs rarely and is a late sign.
3. hypertensive episodes,
4. bradycardia,
5. hyperventilation,
6. profuse sweating,
7. local or general myoclonus,
8. focal fits or
9. decerebrate posturing.
5. Hypotension
6. Spasticity and hyperreflexia but Plantar responses are flexor.

Investigations

1. LFT
1. S bilirubin ↑
2. SGPT, SGOT ↑↑: (after paracetamol overdose, reaching 100–500 times normal) not helpful in determining prognosis.
2. Prothrombin time ↑↑ and factor V ↓.
3. An EEG is sometimes helpful in grading the encephalopathy.
4. Ultrasound will define liver size and may indicate underlying liver pathology. 

Investigations to determine the cause

1. Toxicology screen of blood and urine
2. HBsAg, IgM anti-HBc
3. IgM anti-HAV
4. Anti-HEV, HCV, cytomegalovirus, herpes simplex, Epstein–Barr virus
5. Caeruloplasmin, serum copper, urinary copper, slit-lamp eye examination
6. Autoantibodies: ANA, Anti-smooth muscle antibody, Liver-kidney microsomal antibody, Soluble liver antigen
7. Immunoglobulins
8. Ultrasound of liver and Doppler of hepatic veins

Monitoring of the Patient

 Clinical

Cardiorespiratory

• Pulse
• Blood pressure
• Central venous pressure
• Respiratory rate 

Neurological

• Intracranial pressure monitoring (ICP is measured by pressure transducers that are inserted directly into the brain tissue)
• Conscious level 

Fluid balance

• Hourly output (urine, vomiting, diarrhoea)
• Input: oral, intravenous 

Investigations

1. Arterial blood gases
2. Peripheral blood count (including platelets)
3. Electrolyte
4. Calcium, S. Magnesium
5. Creatinine, Blood urea
6. Glucose (2-hourly in acute phase)
7. Prothrombin time
8. Infection surveillance
1. Cultures: blood, urine, throat, sputum, cannula sites
2. Chest X-ray

Management

There is no specific treatment.

Patients should be managed in a specialized unit (HDU or ICU).

Conservative treatment aims to maintain life in the hope that hepatic regeneration will occur.

The goal of therapy is to support the patient by

1. Maintenance of fluid balance,
2. Support of circulation and respiration,
3. Control of bleeding,
4. Correction of hypoglycemia and
5. Treatment of other complications of the comatose state

Transfer criteria to specialized units

• INR >0
• Presence of hepatic encephalopathy
• Hypotension after resuscitation with fluid
• Metabolic acidosis
• Prothrombin time (seconds) > interval (hours) from overdose (paracetamol cases) 

Overall management

1. Protein intake should be restricted^H.
2. Oral lactulose or neomycin
3. 20% mannitol (1 g/kg bodyweight) should be infused intravenously if cerebral oedema develops; this dose may need to be repeated.
4. 10% dextrose infusion (checked by 2-hourly dipstick testing),
5. Hyponatraemia should be corrected with hypertonic saline.
6. Coagulopathy is managed with intravenous vitamin K, platelets, blood or fresh frozen plasma.
7. Haemorrhage may be a problem and patients are given a proton pump inhibitor (PPI) to prevent gastrointestinal bleeding.
8. Prophylaxis against bacterial and fungal infection is routine. Suspected infection should be treated immediately with suitable antibiotics.
9. Correction electrolyte imbalance with potassium, calcium, phosphate and magnesium supplements.
10. N-acetylcysteine therapy may improve outcome, particularly in patients with paracetamol overdose.
11. Renal and respiratory failure should be treated as necessary.
12. Orthotopic liver transplantation is done with increasing frequency with excellent results.

Complication

• Cerebral oedema develops in 80% case with intracranial hypertension and brain herniation.
• Hypoglycaemia
• Metabolic acidosis
• Bacterial and fungal infections,
• Gastrointestinal bleeding,
• Respiratory arrest,
• Kidney failure (hepatorenal syndrome and acute tubular necrosis)
• Multi-organ failure (hypotension and respiratory failure)
• Pancreatitis

Prognosis

Poor prognostic variables indicating a need for liver transplantation

Non-paracetamol (three of following five)

1. Drug or non-A–E hepatitis
2. Age <10 and >40 years
3. Interval from onset of jaundice to encephalopathy >7 days
4. Serum bilirubin >300 μmol/L
5. Prothrombin time >50 s (or >100 s in isolation)

Paracetamol (acetaminophen)

• Arterial pH <3 (after resuscitation, 7.25 on acetylcysteine) or

• Serum creatinine >300 μmol/L and

• PT >100 s and

• Grade III–IV encephalopathy 

• In mild cases two-thirds of the patients will survive.
• The outcome of severe cases is related to the aetiology.
• In special units, 70% of patients with paracetamol overdosage and grade IV coma survive and
• 30–40% patients with HAV or HBV hepatitis survive.

Further reading

• Davidsone Principles & Practice of Medicine 22^nd edition
• Kumar & Clark's Clinical Medicine 8^th edition
• Harrison's Principles of Internal Medicine 18^th edition