Acute Liver (Hepatic) Failure

Overview

Overview Acute liver failure is a rare but life-threatening critical illness that occurs most often in patients who do not have preexisting liver disease. Acute liver failure is seen most commonly in previously healthy adults in their 30s and presents unique challenges in clinical management. The clinical presentation usually includes hepatic dysfunction, abnormal liver biochemical values, and coagulopathy; encephalopathy may develop, with multiorgan failure and death occurring in up to half the cases

Definition
Acute liver failure (ALF): is a rare syndrome defined by a rapid decline in hepatic function characterised by jaundice, coagulopathy (INR >1.5), and hepatic encephalopathy in patients with no evidence of prior liver disease
Fatty liver disease: Fat accumulation in the liver as globules. Can be non-alcoholic or alcoholic. Common cause of chronic liver disease and eventually liver cirrhosis
Liver Cirrhosis: irreversible damage or scarring to the liver as a result of advanced liver disease (such as hepatitis) that stops the liver functioning, potentially leading to liver failure.

Anatomy and Physiology

Watch Anatomy and Physiology of the Liver

Watch Liver Physiology

Risk Factors

Travelling overseas - hepatitis
Age
Cardiorespiratory failure
Mental illness

Signs and Symptoms

Clinical Presentation of Acute Liver Injury

Jaundice (defining feature)
Pruritis
Symptoms of hepatic encephalopathy (Grading Encephalopathy is Important!)
Abdominal pain
Nausea/vomiting
Malaise

Remember The presence of jaundice and its relation to the onset of hepatic encephalopathy is important in the assessment of prognosis and further characterisation of ALF

Clinical Examination of Acute Liver Failure

Signs of hepatic encephalopathy (Grading is important!)
- Confusion, somnolence, coma
- Hyperreflexia
- Nystagmus
- Asterixis
- Clonus

Asterix: tremor of the hand when the wrist is extended, sometimes said to resemble a bird flapping its wings. Causes include hepatic encephalopathy, uraemic syndrome (renal failure) and pulmonary insufficiency (↑CO2)

Jaundice
Vesicular skin lesions - herpes simplex virus
Kayser-Fleisher rings - Wilson disease
Fever
Right upper quadrant tenderness and hepatomegaly
Ascites
Signs of intravascular volume depletion, such as orthostatic hypotension
Features of preeclampsia, such as hypertension (HELLP syndrome)

GRADING SYSTEM FOR HEPATIC ENCEPHALOPATHY
Grade	Mental status	Asterixis	EEG
I	Euphoria/depression	Yes/no	Usually normal
	Mild confusion
	Slurred speech
	Disordered sleep
II	Lethargy	Yes	Abnormal
	Moderate confusion
III	Marked confusion	Yes	Abnormal
	Incoherent
	Sleeping but arousable
IV	Coma	No	Abnormal

Classification

Acute hepatic failure is defined by a rapid decline in hepatic function characterised by jaundice, coagulopathy (INR >1.5), and hepatic encephalopathy in patients with no evidence of prior liver disease. Therefore:

First exclude underlying chronic liver disease (ex. cirrhosis). The following signs suggest chronic liver disease or cirrhosis is underlying acute presentation:
- Splenomegaly
- Spider angiomata
- Palmar errythema
- Ascites

Watch Video Liver Cirrhosis

King's Classification	Features
Hyperacute liver failure	Encephalopathy within 7 days of onset of jaundice
Acute liver failure	8-28 days from jaundice to encephalopathy
Subacute liver failure	29-72 days from jaundice to encephalopathy

Side note Ammnonia levels don't always correlate with severity of encephalopathy

Hepatic encephalopathy is a neuropsychiatric disorder in patients with liver dysfunction (personality changes, intellectual impairment, reduced consciousness). This is due to diversion of portal blood into the systemic circulation via collateral resulting in increased about of toxins that are not cleared by the liver. Exposure of the brain to excessive concentrations of ammonia and other toxins can cause neurotoxicity.

Differential Diagnosis

Remember Acute liver failure is caused by something. Rule out viral and drug induced causes. Keep in mind the differentials below

Severe acute hepatitis
Cholestasis

Aetiology

Determining the aetiology of acute liver failure requires a combination of history taking, laboratory tests, and imaging studies.

Paracetamol hepatotoxicity (50% - most common in developed countries)
- Equally divided between intentional and unintentional cases
Idiosyncratic drug-induced liver injury (11%)
Viruses - Common in developing countries
- Hepatitis A
- Hepatitis B
- Hepatitis E
Autoimmune hepatitis
Ischaemic hepatitis - patients with underlying cardiac/respiratory failure
Pregnancy related syndrome
Budd-Chiari syndrome
Mushroom ingestion - Amanita phalloides
Wilson's disease
Malignancy

Remember Viral and drug-induced hepatitis are the most common causes of acute liver failure in adults

DRUGS ASSOCIATED WITH LIVER INJURY
Drug Class	Examples
Herbal and dietary supplements	Body building and weight loss supplements, Chinese herbs and many more...
Antimicrobial	Many...
Analgesics	NSAIDs, paracetamol
Antiepileptic drugs	carbamazepine, lamotrigine, phenytoin, valproate
Illicit drugs	MDMA, cocaine
Immunomodulatory drugs	Azathioprine, TNF-α inhibitors, methotrexate, interferon-beta
Antineoplastic drugs	Flutamide, ipilimumab
Antiretroviral drugs	Ritonavir, efavirenz
Cardiovascular drugsdrugs	Amiodarone, methyldopa
Psychotropic drugs	Duloxetine, chlorpromazine

Investigations

Bedside

ECG
Blood glucose - may be dangerous low

Serology

LFT - Often elevated levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP)
Prothrombin time/INR
- INR >1.5 is a defining feature of ALF
EUC - renal failure is often a complication
Serum Ammonia - may be dramatically elevated → risk of intracranial hypertension
FBC
Coagulation studies
ABG
Amylase/Lipase
Paracetamol level
Viral Hepatitis serology (Hep A, B, C, D, E)
ANA - for autoimmune hepatitis
Ceruloplasmin - if Wilson disease suspected

Imaging

Chest X-ray
CT abdomen- for evidence of Budd Chari syndrome and also in cases of severe encephalopathy
Liver ultrasound +/- Fibroscan - if chronic liver disease suspected

Management

Initial resuscitation

ABCD
Determination of aetiology
Assessment of the severity of the disease and the associated prognosis
- Investigations specified above
Treatment of specific cause
- Acute acetaminophen overdose is treated with N-acetylcysteine
- Hepatitis - oral nucleoside or nucleotide analogue
- Suspected mushroom (Amanita phalloides) poisoning
  - IV fluids + gastric lavage + activated charcoal
  - benzylpenicillin
  - acetylcysteine
- Autoimmune hepatitis - glucocorticoids

Remember Regular neurological observations - for patients with rapid progression of encephalopathy/ agitation/ coma and early intubation is recommended to protect airway

Supportive Treatment

Monitoring - Daily laboratory testing
- LFTs
- Coagulation profile
- FBC
- EUC
- ABG
- CMP
- Glucose
Prevention or treatment of complications
- Cardiovascular
  - Hypotension - Vasopressors (noradrenaline)
  - Decrease cardiac output and right ventricular failure - assess with echocardiogram
- Respiratory - 30% 0f cases
  - Pulmonary oedema
  - Infection
- Neurological
  - Encephalopathy - sedate and prophylactic osmotherapy → ↓ammonia →↓intracranial hypertension
  - Intracranial hypertension - hyperventilation to induce hypocapnia →↓intracranial hypertension
    - ?Lactulose
  - Seizures → Lamotrogine
- Metabolic and renal - 50% of cases common in the elderly
  - Hypoglycaemia - dextrose infusion
  - Hyponaturaemia - Hypertonic saline
  - Hypokalaemia - KCl IV
  - Acute renal failure
- Haematological
  - Coagulopathy - Vitamin K, Fresh frozen plasma
Liver transplantation when spontaneous survival is considered unlikely
Possible use of liver support devices

Complications and Prognosis

Complications

Cardiovascular
- Hypotension
- Decrease cardiac output and right ventricular failure
Respiratory - 30% 0f cases
- Pulmonary oedema
- Infection
Neurological
- Encephalopathy
- Intracranial hypertension
Metabolic and renal - 50% of cases common in the elderly
- Hypoglycaemia
- Hyponaturaemia
- Acute renal failure
Haematological
- Coagulopathy

Side note Intracranial hypertension from severe cerebral edema remains a feared complication and is a leading cause of death worldwide among patients with acute liver failure.

Prognosis Only 40 percent of patients with acute liver failure recover spontaneously, leaving many in need of a liver transplantation, and even those who do eventually recover are often gravely ill

Liver Transplant

Liver transplantation The decision to proceed with liver transplantation depends upon the probability of spontaneous hepatic recovery. Results in average 1-yr survival rates of about 80%. Transplantation is thus recommended if prognosis without transplantation is worse

CRITERIA FOR LIVER TRANSPLANTATION IN PATIENTS WITH ALF
Factors	Kings College Criteria	Clichy
Age	Yes	Yes
Cause	Yes	No
Encephalopathy	Yes	Yes
Bilirubin levels	Varies	No
Coagulopathy	Yes	Yes