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Acute liver failure results from the loss of normal function of hepatic tissue occurring over a short period of time. It results from the loss of the metabolic, secretory, and regulatory effects of the liver cells. This leads to the rapid accumulation of toxic substances, which then manifests in the patient as an altered [[sensorium]], [[cerebral edema]], [[hemodynamic]] abnormalities, and even [[multiorgan failure]]. | |||
Cytotoxic and vasogenic cerebral edema have been implicated in acute liver failure (ALF) with a preponderance of experimental data favouring cytotoxic mechanisms. Astrocyte swelling is a consistent neuropathological finding in human ALF and ammonia plays a definitive role. The mechanism(s) by which ammonia induces astrocyte swelling remains unclear but glutamine plays a central role inducing oxidative stress, energy failure and ultimately astrocyte swelling. Although complete breakdown of the blood-brain barrier is not evident in human ALF, increased permeation to water and ammonia has been demonstrated. | Cytotoxic and vasogenic cerebral edema have been implicated in acute liver failure (ALF) with a preponderance of experimental data favouring cytotoxic mechanisms. Astrocyte swelling is a consistent neuropathological finding in human ALF and ammonia plays a definitive role. The mechanism(s) by which ammonia induces astrocyte swelling remains unclear but glutamine plays a central role inducing oxidative stress, energy failure and ultimately astrocyte swelling. Although complete breakdown of the blood-brain barrier is not evident in human ALF, increased permeation to water and ammonia has been demonstrated. | ||
Revision as of 15:04, 2 November 2017
Acute liver failure results from the loss of normal function of hepatic tissue occurring over a short period of time. It results from the loss of the metabolic, secretory, and regulatory effects of the liver cells. This leads to the rapid accumulation of toxic substances, which then manifests in the patient as an altered sensorium, cerebral edema, hemodynamic abnormalities, and even multiorgan failure. Cytotoxic and vasogenic cerebral edema have been implicated in acute liver failure (ALF) with a preponderance of experimental data favouring cytotoxic mechanisms. Astrocyte swelling is a consistent neuropathological finding in human ALF and ammonia plays a definitive role. The mechanism(s) by which ammonia induces astrocyte swelling remains unclear but glutamine plays a central role inducing oxidative stress, energy failure and ultimately astrocyte swelling. Although complete breakdown of the blood-brain barrier is not evident in human ALF, increased permeation to water and ammonia has been demonstrated.
Cerebral edema in acute liver failure can be vasogenic as well as cytotoxic. The increased ammonia concentration in liver failure in combination with the glutamine produced by the astrocytes causes excess levels of glutamine synthesis with the help of glutamine synthetase. The excess glutamine is cytotoxic and can disturb the osmotic gradient and cause brain swelling. In acute liver failure, the increasesd levels of nitric oxide in the circulation can also disrupt the cerebral autoregulation.
Cerebral edema occurs due to damage to the blood brain barrier and can cause altered sensorium and increased intracranial pressure. Acute liver failure causes increased ammonia concentrations due to the failure of the detoxification system that occurs through the liver. The increased levels of ammonia in combination with the glutamate produced by the astrocytes of brain, cause excess levels of glutamine produced through the enzyme glutamine synthetase. The accumulation of glutamine in high concentrations in the brain is what causes cerebral edema. In acute liver failure, there are also increased levels of nitric oxide in the circulation. Nitric oxide is a potent vasodilator and causes a disruption of the cerebral blood flow. This in turn disrupts cerebral auto-regulation. Multiorgan failure occurs due to severe hypotension which is caused by the decreased systemic vascular resistance.
Classification
Acute liver failure may be classified on the basis of the duration of the symptoms between the onset of jaundice to the onset of encephalopathy. The different classification systems based on the number of weeks from the appearance of jaundice to the encephalopathy are:
| Classification system | Duration |
|---|---|
| O’Grady System |
|
| Bernuau System |
|
| Japanese System |
|
The 1993 classification defines three subcategories based on the severity and duration of the acute liver failure. [1] The importance of this method of classification is that the pace of the disease evolution strongly influences prognosis. The underlying etiology causing the development of acute liver failure is the other significant determinant in regards to prognosis.[2] This classification system is based upon the duration between onset of jaundice to onset of encephalopathy.
| Classification | Time |
|---|---|
| Hyperacute | 1 week |
| Acute | 1 week - 1 month |
| Subacute | 1 week - 3 months |
Acute liver failure can also be classified into fulminant or subfulminant. Both of these forms have a poor prognosis. It is based upon the duration between onset of hepatic illness, to the development of encephalopathy.[3]
| Classification | Time |
|---|---|
| Fulminant | within 2 months |
| Subfulminant | within 2 months to 6 months |
O’Grady System
The classification of encephalopathy according to the O’Grady system is as follows.[4]
Hyperacute
Hyperacute encephalopathy is an encephalopathy that occurs within 7 days of onset of jaundice.
Acute
Acute encephalopathy is an encephalopathy that occurs within an interval of 8 to 28 days from onset of jaundice.
Subacute
Subacute encephalopathy is an encephalopathy that occurs within 5 to 12 weeks of onset of jaundice.
Bernuau System
The classification of encephalopathy according to the Bernuau system is as follows.[5]
Fulminant
Fulminant encephalopathy is an encephalopathy that occurs within 2 weeks of onset of jaundice.
Subfulminant
Subfulminant encephalopathy is an encephalopathy that occurs within an interval of 2 to 12 weeks from onset of jaundice.
Japanese System
The classification of encephalopathy according to the Bernuau system is as follows.[6]
Fulminant
Fulminant encephalopathy is an encephalopathy that occurs within 8 weeks of onset of jaundice.
Late-Onset
Late onset encephalopathy is an encephalopathy that occurs within an interval of 8 to 24 weeks from onset of jaundice.
Acute
Acute encephalopathy is an encephalopathy that occurs within 10 days of onset of jaundice
Subacute
Subacute encephalopathy is an encephalopathy that occurs within an interval of 11 to 56 days from onset of jaundice
- ↑ O'Grady JG, Schalm SW, Williams R. Acute liver failure: redefining the syndromes. Lancet 1993;342:273-5. PMID 8101303.
- ↑ O'Grady JG (2005). "Acute liver failure". Postgraduate medical journal. 81 (953): 148–54. doi:10.1136/pgmj.2004.026005. PMID 15749789.
- ↑ Williams R (1996). "Classification, etiology, and considerations of outcome in acute liver failure". Seminars in Liver Disease. 16 (4): 343–8. doi:10.1055/s-2007-1007247. PMID 9027947. Retrieved 2012-10-26. Unknown parameter
|month=ignored (help) - ↑ O'Grady, JG.; Schalm, SW.; Williams, R. (1993). "Acute liver failure: redefining the syndromes". Lancet. 342 (8866): 273–5. PMID 8101303. Unknown parameter
|month=ignored (help) - ↑ Bernuau, J.; Rueff, B.; Benhamou, JP. (1986). "Fulminant and subfulminant liver failure: definitions and causes". Semin Liver Dis. 6 (2): 97–106. doi:10.1055/s-2008-1040593. PMID 3529410. Unknown parameter
|month=ignored (help) - ↑ Mochida, S.; Nakayama, N.; Matsui, A.; Nagoshi, S.; Fujiwara, K. (2008). "Re-evaluation of the Guideline published by the Acute Liver Failure Study Group of Japan in 1996 to determine the indications of liver transplantation in patients with fulminant hepatitis". Hepatol Res. 38 (10): 970–9. doi:10.1111/j.1872-034X.2008.00368.x. PMID 18462374. Unknown parameter
|month=ignored (help)