The liver is an essential organ with a wide variety of functions. It’s regenerative role is impressive but it is still susceptible to acute insults that may lead to failure. There is some overlap with an acute deterioration of chronic disease, although there are differences between these and that is considered in conjunction with chronic liver disease.
The profile of acute liver failure is generally described based on the speed of onset of encephalopathy from the time of onset of jaundice (O’Grady system):
Hyperacute (<1 week)
Acute (1-4 weeks)
Subacute (4-12 weeks)
This can be divided into causative agent
Recreational - alcohol, ecstasy, methamphetamines
Drug reactions - antibiotics, anticonvulsants, anti-TB, halothane
There can be a wide-spectrum of presentations of acuity. An A to E assessment may be needed in some cases, with liver failure presenting as a severe multisystem disease, much like septic shock. Much of the time the presentation will be much less acute, allowing a detailed history and examination.
Key factors in the history include:
Relevant past medical history
Recreational, including alcohol and IVDU
Family history of related conditions
Key features include:
Mental state changes - see encephalopathy assessment
Jaundice - including scleral examination
This is a key feature of liver failure, and the clinical features can be considered as involving:
Level of alertness/consciousness
Personality and behaviour
Encephalopathy grading (West Haven Criteria):
Change in behaviour, minimal change in conscious level:
change in sleep-wake cycle
Slowed performance of tasks e.g. arithmetic
Gross deficits of mental tasks, some conscious level changes:
Notable impact on conscious level, severe impact on cognitive tasks
sleeping most of the time but arousable to vocal stimuli
Comatose, unrousable to pain, decorticate or decerebrate posturing
Grade 0 describes subclinical hepatic encephalopathy which may involve some deficits detectable on detailed psychometric testing e.g. memory and coordination changes.
The pathophysiology of ALF can lead to CVS changes due to the impact on vasoactive mediators. This can lead to a high output shock with a vasodilation picture.
Impaired synthesis of clotting factors is a key feature of ALF. However, this affects both pro and anti-coagulant factors, so the rate of spontaneous bleeding is described as low.
ALF is an immunocompromised state. Extra care is needed in infection control measures and increased vigilance for infective causes of deterioration.
Markers of injury
Alk phos (may be raised less or normal)
Markers of impaired function
Other viral - CMV, HSV
Smooth muscle antibody
Eosiniphillia may be present in drug reactions
CT +/- contrast
US with portal vein doppler
Head imaging may be used in cases of altered neurological state to assess for alternative diagnoses as well as having the potential to demonstrate cerebral oedema. EEG can demonstrate encephalopathy.
A liver biopsy may be indicated in some cases where the aetiology is unclear. This is rarely performed in ALF due to the high risk of bleeding, although the transjugular route may reduce this risk. The results of biopsy may also not be helpful due to a tendency for patchy and non-specific changes.
Management of these patients can be challenging and involvement of specialist centres may be needed. The key components of care can be considered as:
Supportive care is an essential part of the management of all patients. Much of this will overlap with general supportive care principles. Key components specific to ALF include:
Reducing ammonia production
Managing raised ICP
Reducing ammonia production is a key part in reducing the encephalopathy. The components may include:
Lactulose is a non-absorbable carbohydrate which is metabolised by gut bacteria, producing acidic products (lactate and acetate). The lower luminal pH results in more shift to NH4+ form rather than NH3, which due to its ionised state is less absorbable. There may also be effects of speeding gut transit and changes to the gut flora.
Raised ICP is a potential complication of ALF. Supportive strategies are mostly the same as for ICP generally. Efforts are also employed to reduce production of ammonia as above. Renal replacement therapy may also be employed to reduce ammonia levels, and thereby cerebral oedema. ICP monitoring is challenging due to the increased risk of bleeding in these patients.
Routine correction of coagulopathy is not recommended, partly due to the mixed clotting abnormalities described, and partly because of the potential impact on transplant assessment (the INR is a key feature). It is generally only performed to provide cover for high risk interventions. Ensuring vitamin K deficiency is not present is important, but more of a problem in patients with chronic liver disease.
The concept of reducing protein intake has been described to reduce hepatic encephalopathy as part of reducing ammonia production. However, this is not well supported, and the consequences of impaired nutrition would seem to outweigh this. This is more relevant for patients with chronic disease, but still an important consideration.
There are some potential specific treatment options that may be possible in some disease processes e.g. paracetamol overdose with N-acetylcysteine. Removing the precipitant is a key feature of managing drug induced disease.
This may be the required treatment for some patients. This is not a universally available option, nor a small undertaking. A useful question is - “Is the chance of them dying in the next year from this liver failure, higher than the chance of them dying from a liver transplant”.
This is a key part of the problem of liver failure, both acutely and chronically. A key differentiation is between that with normal ICP and that with raised ICP. As a simple summary, acute liver failure is more likely to result in raised ICP, as there is less time for compensatory changes to occur.
A key part of the pathophysiology is the accumulation of ammonia (NH3) This is produced in the gut primarily through bacterial metabolic action. Normally it is well metabolised by the liver and converted to urea through the urea cycle. In liver failure, this process does not occur to the same degree, and there can be shunting around the liver e.g. when there is portal hypertension. In the brain this causes a metabolic shift in the brain with increased glutamate production and reduced ATP production. There is also increase production of glutamine which has an effect on cellular oncotic pressure, leading to oedema, as well as oxidative stress.
However, plasma ammonia levels don’t correlate perfectly with encephalopathy, and other factors appear to be contributory, including: