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.<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]] 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]] 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 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.
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 have 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.
* 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.
The evaluation of a patient diagnosed with acute liver failure should begin immediately to identify the cause of the acute liver failure. This is crucial because in some cases, early diagnosis and treatment may improve the patient's prognosis. In addition, timely evaluation is required to identify patients who may require urgent liver transplantation
Many of the initial symptoms in patients with acute liver failure are nonspecific [14]. They include:
●Fatigue/malaise
●Lethargy
●Anorexia
●Nausea and/or vomiting
●Right upper quadrant pain
●Pruritus
●Jaundice
●Abdominal distension from ascites
As the liver failure progresses, patients who were initially anicteric may develop jaundice, and those with subtle mental status changes (eg, lethargy, difficulty sleeping) may become confused or eventually comatose.
Acute liver failure refers to the development of severe acute liver injury with encephalopathy and impaired synthetic function (INR of ≥1.5) in a patient without cirrhosis or preexisting liver disease [2,3]. While the time course that differentiates acute liver failure from chronic liver failure varies between reports, a commonly used cutoff is an illness duration of <26 weeks.
Acute liver failure may also be diagnosed in patients with previously undiagnosed Wilson disease, vertically acquired hepatitis B virus, or autoimmune hepatitis, in whom underlying cirrhosis may be present, provided the disease has been recognized for <26 weeks. On the other hand, patients with acute severe alcoholic hepatitis, even if recognized for <26 weeks, are considered to have acute-on-chronic liver failure since most have a long history of heavy drinking. The approach to such patients is discussed elsewhere. (See "Clinical manifestations and diagnosis of alcoholic fatty liver disease and alcoholic cirrhosis" and "Prognosis and management of alcoholic fatty liver disease and alcoholic cirrhosis".)
Acute liver failure can be subcategorized based upon how long the patient has been ill and various cutoffs have been used. We classify acute liver failure as hyperacute (<7 days), acute (7 to 21 days), or subacute (>21 days and <26 weeks). In patients with hyperacute or acute liver failure, cerebral edema is common, whereas it is rare in subacute liver failure [4]. On the other hand, renal failure and portal hypertension are more frequently observed in patients with subacute liver failure. These subcategories have been associated with prognosis, but the associations reflect the underlying causes, which are the true determinants of prognosis. As an example, patients with hyperacute liver failure tend to have a better prognosis than those with subacute liver failure. The better prognosis is related to the fact that these patients often have acetaminophen toxicity or ischemic hepatopathy, diagnoses associated with a better prognosis than many of the disorders that may result in subacute liver failure, such as Wilson disease [2].
By definition, patients with acute liver failure have severe acute liver injury (demonstrated by liver test abnormalities) with signs of hepatic encephalopathy and a prolonged prothrombin time (INR ≥1.5). Other clinical manifestations may include jaundice, hepatomegaly, and right upper quadrant tenderness.
Symptoms — Many of the initial symptoms in patients with acute liver failure are nonspecific [14]. They include:
●Fatigue/malaise
●Lethargy
●Anorexia
●Nausea and/or vomiting
●Right upper quadrant pain
●Pruritus
●Jaundice
●Abdominal distension from ascites
As the liver failure progresses, patients who were initially anicteric may develop jaundice, and those with subtle mental status changes (eg, lethargy, difficulty sleeping) may become confused or eventually comatose.
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 [[Hyperammonemia|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]].
Electrocardiogram (ECG) may show J wave, sinus bradycardia and prolongation of all ECG intervals.
Serum electrolytes (including potassium and calcium)
BUN and creatinine
Serum hemoglobin, white blood cell, and platelet counts ( Raised HCT due to volume contraction)
Coagulation profile (clotting factors impairment)
Serum lactate ( lactic acidosis)
Creatine kinase (Rhabdomylosis)
Arterial blood gas
CXR
* Mild hypothermia: core temperature 32 to 35°C ; patient presents with confusion, tachycardia, and increased shivering.
Moderate hypothermia: 28 to 32°C patient presents with lethargy, bradycardia and arrhythmia and decreased shivering.
Severe hypothermia: below 28°C patient presents with coma, hypotension, arrhythmia, pulmonary edema, and rigidity.
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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
Hyperacute (0 - 1 week)
Acute ( From 2nd week - 4 weeks)
Subacute ( From 4th week - 12 weeks)
Bernuau System
Fulminant ( 0 - 2 weeks)
Subfulminant ( 2 weeks - 12 weeks)
Japanese System
Fulminant (0 - 8 weeks)
Acute ( 0 - 1.5 weeks)
Subacute ( 1.5 weeks - 8 weeks)
Late-Onset ( 8 weeks - 12 weeks)
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.
↑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. PMID18462374. Unknown parameter |month= ignored (help)