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Liver failure
Liver failure

Liver failure

In this CCC we will cover acute liver failure. Chronic liver failure occurs as a result of cirrhosis, for which more detail can be found here. Acute-on-chronic liver failure (ACLF) is a syndrome characterised by acute and severe hepatic abnormalities resulting from different types of insults, in patients with underlying chronic liver disease or cirrhosis but, in contrast to decompensated cirrhosis, has a high short-term mortality, mimicking the prognosis of acute liver failure.

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ACUTE LIVER FAILURE

Acute liver failure (ALF) is a rare occurrence that is defined by 3 features:

  1. Jaundice
  2. Coagulopathy
  3. Hepatic encephalopathy

It is a rare disease with <10 cases per million per year. 2/3rds of the cases are female, with the mean age being 38 years old.

Pathophysiology

ALF has many causes, which we will discuss, but most of these lead to massive hepatocyte necrosis which then causes liver failure.

The main causes of ALF include:

  1. Paracetamol overdose - accounts for approximately 46% of all cases.
  2. Pregnancy
  3. Alcohol
  4. Drug-induced liver injury - 11% of cases. Antimicrobials most commonly (after paracetamol).
  1. Acute hepatitis B - 7%. Acute hepatitis A can also cause it (1%) of cases.
  2. Autoimmune hepatitis - 7%
  3. Ischaemic hepatitis - 7%
  4. Unspecified makes up 25% of cases.

🔢 Classification

The classification is based on the onset of jaundice → development of encephalopathy. This interval (and aetiology) have a significant impact on the prognosis of the disease and so it is valuable to classify it.

Nowadays, we can classify liver failure as:

  • Hyperacute - <7 days.
  • Acute - 8-28 days
  • Subacute - 29 days - 12 weeks.

Previously, we could classify it as either:

  1. Fulminant - if occurring within 2 weeks.
  2. Subfulminant - if occurring between 2-12 weeks.

⚠️ Risk factors

  • Chronic alcohol abuse - not only for the devlopment of alcoholic hepatitis and ALD, but also it is a major risk factor for unintentional paracetamol overdose. Their threshold for paracetamol is also lower, which therefore increases their likelihood of having an overdose.
  • Poor nutritional status - also increases risk of paracetamol hepatotoxicity, and increases risk of acute viral hepatitis.
  • Female sex - due to pregnancy and also at increased risk of drug-induced liver injury.
  • Pregnancy - increased risk of hepatitis E during pregnancy associated with an increased viral load. Another big concern is HELLP syndrome (more on HELLP syndrome below).
  • Chronic hepatitis B - especially when chronic hepatitis B is combined with hepatitis D infection.

😷 Presentation

  1. Jaundice - this is the defining feature of ALF.
  2. Coagulopathy - raised PT.
  3. Hepatic encephalopathy
    1. Grade 1 - subtly impaired awareness, sleep alterations, shortened attention span, arousal or anxiety, oriented in time and space.
    2. Grade 2 - lethargy, disorientation, personality changes, inappropriate behaviour, dyspraxia, asterixis.
    3. Grade 3 - somnolence, marked confusion, gross disorientation, bizarre behaviour, hyper-reflexia, nystagmus, clonus, rigidity.
    4. Grade 4 - coma.

Other features include:

  • Abdominal pain
  • Nausea and vomiting
  • Hypoalbuminaemia
  • Renal failure - hepatorenal syndrome.

It is important to be aware of some notable absences which may be suggestive of chronic liver disease, as opposed to ALF:

  • Absence of chronic liver disease
  • Absence of splenomegaly
  • Absence of spider naevi, palmar erythema and ascites

🔍 Investigations

🧪
Investigations for ALF:

There are plenty of studies one could potentially do. It all is dependant on the patients background and history. Remember that prothrombin time and albumin levels are better markers of liver function than LFTs. In the acute setting, prothrombin time is a better indicator.

  • LFTs
    • Hyperbilirubinaemia
    • Elevated AST, ALT, ALP - ALP elevated more than 5x of normal has 90% sensitivity.
  • Prothrombin time/INR - prolonged PT or INR >1.5 is a defining feature.
  • FBC
    • Leukocytosis - may suggest infection.
    • Thrombocytopenia may suggest pre-existing advanced liver disease.
  • Blood type and screen - in case blood transfusion is needed.
  • ABG - metabolic acidosis may be present and an elevated lactate too.
  • Paracetamol level - may be elevated but if not it does not exclude paracetamol hepatotoxicity. Acetylcysteine should be given in all suspected cases.
  • Pregnancy test
  • Viral hepatitis serologies and PCR
  • Autoimmune hepatitis markers

🧰 Management

🏥
ALF management:
  1. ICU management - this is mandatory when hepatic encephalopathy is present. A plethora of complications will be assessed such as sepsis, cerebral oedema, haemodynamic instability, renal failure. Tracheal intubation may be needed if there is advanced encephalopathy. Analgesia should also be given. We should aim to feed the patient enterally early on.
  2. Transplantation assessment
  3. Neurological status and advanced encephalopathy monitoring
  4. Blood glucose, electrolytes and cultures monitoring

Depending on the aetiology we need to provide additional management:

  • Paracetamol overdose - acetylcysteine
  • Herpes simplex hepatitis - aciclovir
  • HELLP syndrome - foetal delivery will improve outcome of the mother.
  • Budd-Chiari syndrome - anti coagulation and TIPS.
  • Acute hepatitis B - tenofovir disproxil or entecavir.