Acute liver failure natural history, complications and prognosis: Difference between revisions
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{{Acute liver failure}} | {{Acute liver failure}} | ||
{{CMG}} {{AE}} | {{CMG}} {{AE}} | ||
==Overview== | ==Overview== | ||
Acute liver failure is a serious condition which can rapidly progress to death if left untreated. Complications of the illness include [[cerebral edema]], [[brain herniation]], [[multi-organ failure]], [[systemic inflammatory response syndrome]], [[metabolic derangements]], [[coagulopathy]], [[hemodynamic instability]], [[coma]], and [[death]].Several prognostic scoring systems have been devised to predict mortality and to identify who will require early liver transplant. Mortality due to acute liver failure used to be as high as 80%, however this statistic has decreased with the advent of liver transplantation, and better intensive care. There are several prognostic indicator scores used for the prediction of mortality, and to assess the suitability of the patient for transplantation. These include [[King's College Criteria|kings college hospital criteria]], [[Model for End-Stage Liver Disease|MELD score]], [[APACHE II]] and Clichy criteria. | Acute liver failure is a serious condition which can rapidly progress to death if left untreated. Complications of the illness include [[cerebral edema]], [[brain herniation]], [[multi-organ failure]], [[systemic inflammatory response syndrome]], [[metabolic derangements]], [[coagulopathy]], [[hemodynamic instability]], [[coma]], and [[death]].Several prognostic scoring systems have been devised to predict mortality and to identify who will require early liver transplant. Mortality due to acute liver failure used to be as high as 80%, however this statistic has decreased with the advent of liver transplantation, and better intensive care. There are several prognostic indicator scores used for the prediction of mortality, and to assess the suitability of the patient for transplantation. These include [[King's College Criteria|kings college hospital criteria]], [[Model for End-Stage Liver Disease|MELD score]], [[APACHE II]] and Clichy criteria. | ||
==Natural History== | ==Natural History== | ||
Acute liver failure is a sudden and severe loss of liver function with evidence of encephalopathy and coagulopathy with elevated prothrombin time (PT) and (INR) in a person without preexisting liver disease. The commonly used time duration for an acute liver disease is < 26 weeks. | Acute liver failure is a sudden and severe loss of liver function with evidence of encephalopathy and coagulopathy with elevated prothrombin time (PT) and (INR) in a person without preexisting liver disease. The commonly used time duration for an acute liver disease is < 26 weeks. | ||
* Acute liver failure can be hyperacute, acute or subacute depending upon how long the patient has signs and symptoms of liver failure. | * Acute liver failure can be hyperacute, acute or subacute depending upon how long the patient has signs and symptoms of liver failure. | ||
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* The timely recognition and treatment of some of the causes of acute liver failure can reverse the condition and may improve the patient's prognosis. The timely evaluation can also help in identifying patients who may require liver transplantation. | * The timely recognition and treatment of some of the causes of acute liver failure can reverse the condition and may improve the patient's prognosis. The timely evaluation can also help in identifying patients who may require liver transplantation. | ||
* In acetaminophen toxicity patients, the time duration between acetaminophen ingestion and treatment with acetylcysteine greatly influence the outcome. | * In acetaminophen toxicity patients, the time duration between acetaminophen ingestion and treatment with acetylcysteine greatly influence the outcome. | ||
==Complications== | ==Complications== | ||
Complications that can develop as a result of acute liver failure are: | |||
===Cerebral Edema and Encephalopathy=== | ===Cerebral Edema and Encephalopathy=== | ||
Complications of acute liver failure can include [[cerebral edema]] | * Complications of acute liver failure can include [[cerebral edema]] and [[hepatic encephalopathy]]. | ||
* The detection of encephalopathy is central to the diagnosis of acute liver failure. It may vary from subtle deficits in higher brain function (e.g. mood, concentration in grade I) to deep coma (grade IV). | |||
* The patients presenting as acute and hyperacute liver failure are at greater risk of developing cerebral edema and grade IV encephalopathy. | |||
* Cerebral edema in acute liver failure can be due to vasogenic and cytotoxic effects. The increased ammonia concentration in liver failure in combination with the glutamine produced by the astrocytes causes excess levels of glutamine with the help of enzyme glutamine synthetase. The excess glutamine is cytotoxic and can disturb the osmotic gradient which can result in brain swelling. In acute liver failure, the increased levels of nitric oxide in the circulation can also disrupt the cerebral autoregulation.<ref>{{cite journal |author=Hazell AS, Butterworth RF |title=Hepatic encephalopathy: An update of pathophysiologic mechanisms |journal=Proc. Soc. Exp. Biol. Med. |volume=222 |issue=2 |pages=99-112 |year=1999 |pmid=10564534 |doi=}}</ref><ref>{{cite journal |author=Larsen FS, Wendon J |title=Brain edema in liver failure: basic physiologic principles and management |journal=Liver Transpl. |volume=8 |issue=11 |pages=983-9 |year=2002 |pmid=12424710 |doi=10.1053/jlts.2002.35779}}</ref>.<ref>{{cite journal |author=Armstrong IR, Pollok A, Lee A |title=Complications of intracranial pressure monitoring in fulminant hepatic failure |journal=Lancet |volume=341 |issue=8846 |pages=690-1 |year=1993 |pmid=8095592 |doi=}}</ref> The aim is to maintain intracranial pressures below 25 mmHg, cerebral perfusion pressures above 50 mm Hg. | |||
===Coagulopathy=== | ===Coagulopathy=== | ||
[[Coagulopathy]] is | * [[Coagulopathy]] is also seen in acute liver failure. The liver has a central role in the synthesis of coagulation factors and some inhibitors of [[coagulation]] and [[fibrinolysis]]. | ||
* The hepatocyte [[necrosis]] leads to impaired [[synthesis]] of [[Coagulation|coagulation factors]] and their inhibitors. The former produces a prolongation in [[Prothrombin time]] which is widely used to monitor the severity of [[hepatic]] injury. | |||
===Renal Failure=== | ===Renal Failure=== | ||
[[Renal failure]] is common, present in more than 50% of | [[Renal failure]] is common, present in more than 50% of acute liver failure patients, either due to original insult such as paracetamol resulting in [[acute tubular necrosis]] or from [[hyperdynamic circulation]] leading to [[hepatorenal syndrome]] or functional renal failure. | ||
* Once the renal failure develops, it is progressive and poor prognosis without liver transplantation. | |||
===Inflammation and Infection=== | ===Inflammation and Infection=== | ||
About 60% of all | * About 60% of all acute liver failure patients fulfil the criteria for [[Systemic inflammatory response syndrome|systemic inflammatory syndrome]] irrespective of presence or absence of infection.<ref>{{cite journal |author=Schmidt LE, Larsen FS |title=Prognostic implications of [[Lactate|hyperlactatemia]], multiple organ failure, and systemic inflammatory response syndrome in patients with acetaminophen-induced acute liver failure |journal=Crit. Care Med. |volume=34 |issue=2 |pages=337-43 |year=2006 |pmid=16424712 |doi=}}</ref>. This often contributes towards [[Multiple organ dysfunction syndrome|multi organ failure]]. | ||
*The impaired host defence mechanisms due to impaired [[Opsonin|opsonisation]], [[chemotaxis]] and intracellular killing substantially increases the risk of sepsis. The sepsis is mostly due [[Gram-positive bacteria|gram positive]] (80%)and fungal (30%) sepsis.<ref name="gimson">{{cite journal |author=Gimson AE |title=Fulminant and late onset hepatic failure |journal=British journal of anaesthesia |volume=77 |issue=1 |pages=90-8 |year=1996 |pmid=8703634 |doi=}}</ref>. | |||
===Metabolic Derangements=== | |||
* The metabolic derrangements seen with acute liver failure include hyponatremia which is due to water retention and shift in [[intracellular]] sodium transport from inhibition of [[Na+/K+-ATPase|Na/K ATPase]]. | |||
* [[Hypoglycaemia]] due to depleted hepatic [[glycogen]] stores. | |||
* [[Hypokalaemia]], [[hypophosphataemia]] and [[metabolic alkalosis]] are often present independent of renal function. | |||
* [[Lactic acidosis]] is seen predominantly in paracetamol overdose. | |||
===Hemodynamic and Cardio-respiratory Compromise=== | |||
* [[Hyperdynamic circulation]] with peripheral [[vasodilator|vasodilatation]] from low [[systemic vascular resistance]] leads to [[hypotension]]. There is a compensatory increase in [[cardiac output]]. | |||
* [[Adrenal insufficiency]] has been documented in 60% of acute liver failure and is likely to contribute in haemodynamic compromise<ref>{{cite journal |author=Harry R, Auzinger G, Wendon J |title=The clinical importance of adrenal insufficiency in acute hepatic dysfunction |journal=Hepatology |volume=36 |issue=2 |pages=395-402 |year=2002 |pmid=12143048 |doi=10.1053/jhep.2002.34514}}</ref>. There is also abnormal [[oxygen]] transport and utilization. Although delivery of oxygen to the tissues is adequate, there is a decrease in tissue oxygen uptake, resulting in [[tissue]] [[hypoxia]] and lactic acidosis<ref>{{cite journal |author=Bihari D, Gimson AE, Waterson M, Williams R |title=Tissue hypoxia during fulminant hepatic failure |journal=Crit. Care Med. |volume=13 |issue=12 |pages=1034-9 |year=1985 |pmid=3933911 |doi=}}</ref>. | |||
* [[Pulmonary]] complication is also seen in acute liver failure.<ref>{{cite journal |author=Trewby PN, Warren R, Contini S, ''et al'' |title=Incidence and pathophysiology of pulmonary edema in fulminant hepatic failure |journal=Gastroenterology |volume=74 |issue=5 Pt 1 |pages=859-65 |year=1978 |pmid=346431 |doi=}}</ref>. Severe lung injury and [[hypoxemia]] result in high mortality. Most cases of severe lung injury is due to [[ARDS]] with or without[[ sepsis]]. Pulmonary [[haemorrhage]], [[pleural effusion]]s, [[atelectasis]], and intrapulmonary shunts also contribute to respiratory difficulty. | |||
==Prognosis== | ==Prognosis== | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief:
Overview
Acute liver failure is a serious condition which can rapidly progress to death if left untreated. Complications of the illness include cerebral edema, brain herniation, multi-organ failure, systemic inflammatory response syndrome, metabolic derangements, coagulopathy, hemodynamic instability, coma, and death.Several prognostic scoring systems have been devised to predict mortality and to identify who will require early liver transplant. Mortality due to acute liver failure used to be as high as 80%, however this statistic has decreased with the advent of liver transplantation, and better intensive care. There are several prognostic indicator scores used for the prediction of mortality, and to assess the suitability of the patient for transplantation. These include kings college hospital criteria, MELD score, APACHE II and Clichy criteria.
Natural History
Acute liver failure is a sudden and severe loss of liver function with evidence of encephalopathy and coagulopathy with elevated prothrombin time (PT) and (INR) in a person without preexisting liver disease. The commonly used time duration for an acute liver disease is < 26 weeks.
- Acute liver failure can be hyperacute, acute or subacute depending upon how long the patient has signs and symptoms of liver failure.
- The natural history of acute liver failure depends on the etiology but generally, cerebral edema mainly presents in hyperacute or acute liver failure, whereas renal shutdown and portal hypertension are the main concerns in the subacute liver failure.
- If left untreated, patients with acute liver failure may initially having nonspecific symptoms such as anorexia, fatigue, nausea or vomiting, diffuse or right upper quadrant abdominal pain or jaundice and can eventually progress to develop confusion and the comatose state and death. A systemic inflammatory response syndrome may also develop. Acute renal failure occurs in up to 50% of cases. The condition can also worsen to the point of causing hemodynamic and cardiovascular compromise.
- The timely recognition and treatment of some of the causes of acute liver failure can reverse the condition and may improve the patient's prognosis. The timely evaluation can also help in identifying patients who may require liver transplantation.
- In acetaminophen toxicity patients, the time duration between acetaminophen ingestion and treatment with acetylcysteine greatly influence the outcome.
Complications
Complications that can develop as a result of acute liver failure are:
Cerebral Edema and Encephalopathy
- Complications of acute liver failure can include cerebral edema and hepatic encephalopathy.
- The detection of encephalopathy is central to the diagnosis of acute liver failure. It may vary from subtle deficits in higher brain function (e.g. mood, concentration in grade I) to deep coma (grade IV).
- The patients presenting as acute and hyperacute liver failure are at greater risk of developing cerebral edema and grade IV encephalopathy.
- Cerebral edema in acute liver failure can be due to vasogenic and cytotoxic effects. The increased ammonia concentration in liver failure in combination with the glutamine produced by the astrocytes causes excess levels of glutamine with the help of enzyme glutamine synthetase. The excess glutamine is cytotoxic and can disturb the osmotic gradient which can result in brain swelling. In acute liver failure, the increased levels of nitric oxide in the circulation can also disrupt the cerebral autoregulation.[1][2].[3] The aim is to maintain intracranial pressures below 25 mmHg, cerebral perfusion pressures above 50 mm Hg.
Coagulopathy
- Coagulopathy is also seen in acute liver failure. The liver has a central role in the synthesis of coagulation factors and some inhibitors of coagulation and fibrinolysis.
- The hepatocyte necrosis leads to impaired synthesis of coagulation factors and their inhibitors. The former produces a prolongation in Prothrombin time which is widely used to monitor the severity of hepatic injury.
Renal Failure
Renal failure is common, present in more than 50% of acute liver failure patients, either due to original insult such as paracetamol resulting in acute tubular necrosis or from hyperdynamic circulation leading to hepatorenal syndrome or functional renal failure.
- Once the renal failure develops, it is progressive and poor prognosis without liver transplantation.
Inflammation and Infection
- About 60% of all acute liver failure patients fulfil the criteria for systemic inflammatory syndrome irrespective of presence or absence of infection.[4]. This often contributes towards multi organ failure.
- The impaired host defence mechanisms due to impaired opsonisation, chemotaxis and intracellular killing substantially increases the risk of sepsis. The sepsis is mostly due gram positive (80%)and fungal (30%) sepsis.[5].
Metabolic Derangements
- The metabolic derrangements seen with acute liver failure include hyponatremia which is due to water retention and shift in intracellular sodium transport from inhibition of Na/K ATPase.
- Hypoglycaemia due to depleted hepatic glycogen stores.
- Hypokalaemia, hypophosphataemia and metabolic alkalosis are often present independent of renal function.
- Lactic acidosis is seen predominantly in paracetamol overdose.
Hemodynamic and Cardio-respiratory Compromise
- Hyperdynamic circulation with peripheral vasodilatation from low systemic vascular resistance leads to hypotension. There is a compensatory increase in cardiac output.
- Adrenal insufficiency has been documented in 60% of acute liver failure and is likely to contribute in haemodynamic compromise[6]. There is also abnormal oxygen transport and utilization. Although delivery of oxygen to the tissues is adequate, there is a decrease in tissue oxygen uptake, resulting in tissue hypoxia and lactic acidosis[7].
- Pulmonary complication is also seen in acute liver failure.[8]. Severe lung injury and hypoxemia result in high mortality. Most cases of severe lung injury is due to ARDS with or withoutsepsis. Pulmonary haemorrhage, pleural effusions, atelectasis, and intrapulmonary shunts also contribute to respiratory difficulty.
Prognosis
Historically mortality has been unacceptably high, being in excess of 80%[9]. In recent years the advent of liver transplantation and multidisciplinary intensive care support have improved survival significantly. At present overall short term survival with transplant is more than 65%[10].
Several prognostic scoring systems have been devised to predict mortality and to identify who will require early liver transplant. These include kings college hospital criteria, MELD score, APACHE II and Clichy criteria.
References
- ↑ Hazell AS, Butterworth RF (1999). "Hepatic encephalopathy: An update of pathophysiologic mechanisms". Proc. Soc. Exp. Biol. Med. 222 (2): 99–112. PMID 10564534.
- ↑ Larsen FS, Wendon J (2002). "Brain edema in liver failure: basic physiologic principles and management". Liver Transpl. 8 (11): 983–9. doi:10.1053/jlts.2002.35779. PMID 12424710.
- ↑ Armstrong IR, Pollok A, Lee A (1993). "Complications of intracranial pressure monitoring in fulminant hepatic failure". Lancet. 341 (8846): 690–1. PMID 8095592.
- ↑ Schmidt LE, Larsen FS (2006). "hyperlactatemia". Crit. Care Med. 34 (2): 337–43. PMID 16424712.
- ↑ Gimson AE (1996). "Fulminant and late onset hepatic failure". British journal of anaesthesia. 77 (1): 90–8. PMID 8703634.
- ↑ Harry R, Auzinger G, Wendon J (2002). "The clinical importance of adrenal insufficiency in acute hepatic dysfunction". Hepatology. 36 (2): 395–402. doi:10.1053/jhep.2002.34514. PMID 12143048.
- ↑ Bihari D, Gimson AE, Waterson M, Williams R (1985). "Tissue hypoxia during fulminant hepatic failure". Crit. Care Med. 13 (12): 1034–9. PMID 3933911.
- ↑ Trewby PN, Warren R, Contini S; et al. (1978). "Incidence and pathophysiology of pulmonary edema in fulminant hepatic failure". Gastroenterology. 74 (5 Pt 1): 859–65. PMID 346431.
- ↑ Rakela J, Lange SM, Ludwig J, Baldus WP (1985). "Fulminant hepatitis: Mayo Clinic experience with 34 cases". Mayo Clin. Proc. 60 (5): 289–92. PMID 3921780.
- ↑ Ostapowicz G, Fontana RJ, Schiødt FV; et al. (2002). "Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States". Ann. Intern. Med. 137 (12): 947–54. PMID 12484709.