Liver failure
Encyclopedia
Acute liver failure is the appearance of severe complications rapidly after the first signs of liver disease (such as jaundice
), and indicates that the liver has sustained severe damage (loss of function of 80-90% of liver cells). The complications are hepatic encephalopathy
and impaired protein synthesis (as measured by the levels of serum albumin
and the prothrombin time
in the blood). The 1993 classification defines hyperacute as within 1 week, acute as 8–28 days and subacute as 4–12 weeks. It reflects the fact that the pace of disease evolution strongly influences prognosis. Underlying etiology
is the other significant determinant of outcome.
, idiosyncratic reaction to medication (e.g. tetracycline, troglitazone
), excessive alcohol intake
(severe alcoholic hepatitis
), viral hepatitis (hepatitis A
or B - it is extremely uncommon in hepatitis C
), acute fatty liver of pregnancy
, and idiopathic (without an obvious cause). Reye syndrome is acute liver failure in a child with a viral infection (e.g. chickenpox
); it appears that aspirin
use may play a significant role. Wilson's disease
(hereditary copper accumulation) may infrequently present with acute liver failure.
and progressing towards portal tracts. The degree of parenchymal inflammation is variable and is proportional to duration of disease
.
Zone 1 (periportal) occurs in phosphorus poisoning or eclampsia.
Zone 2 (midzonal), although rare, is seen in yellow fever.
Zone 3 (centrilobular) occurs with ischemic injury, toxic effects, carbon tetrachloride exposure, or chloroform ingestion. Drugs such as acetaminophen may be metabolized in zone 1 to toxic compounds that cause necrosis on zone 3.
, coma
, brain herniation
and eventually death. Detection of encephalopathy is central to the diagnosis of ALF. It may vary from subtle deficit in higher brain function (e.g. mood, concentration in grade I) to deep coma (grade IV). Patients presenting as acute and hyperacute liver failure are at greater risk of developing cerebral oedema and grade IV encephalopathy. The pathogenesis
remains unclear but is likely to be a consequence of several phenomena. There is a build up of toxic substances like ammonia
, mercaptan, endogenous benzodiazepines and serotonin
/tryptophan
in the brain. This affects neurotransmitter
level and neuroreceptor activation. Autoregulation of cerebral blood flow is impaired and is associated with anaerobic glycolysis
and oxidative stress
. Neuronal cell astrocyte
s are susceptible to these changes and they swell up, resulting in increased intracranial pressure. Inflammatory mediators also play important role.
Unfortunately, signs of elevated intracranial pressure
such as papilloedema and loss of pupillary reflexes are not reliable and occur late in the disease process. CT
imaging of the brain is also unhelpful in detecting early cerebral oedema but is often performed to rule out intra-cerebral bleeding
. Invasive intracranial pressure monitoring via subdural
route is often recommended, however the risk of complications must be weighed against the possible
benefit (1% fatal haemorrhage). The aim is to maintain intracranial pressures below 25 mmHg, cerebral perfusion pressures above 50 mm Hg.
is another cardinal feature of ALF. The Liver has the central role in synthesis of almost all coagulation factors and some inhibitors of coagulation
and fibrinolysis
. Hepatocellular necrosis
leads to impaired synthesis
of many coagulation factors and their inhibitors. The former produces a prolongation in Prothrombin time
which is widely used to monitor severity of hepatic injury.There is significant platelet dysfunction (with both quantitative and qualitative platelet defects). Progressive thrombocytopenia
with loss of larger and more active platelet
is almost universal. Thrombocytopenia with or without DIC
increases risk of intracerebral bleeding.
is common, present in more than 50% of ALF 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. Because of impaired production of urea, blood urea does not represent degree of renal impairment.
irrespective of presence or absence of infection. This often contributes towards multi organ failure
. Impaired host defence mechanism, due to impaired opsonisation, chemotaxis
and intracellular killing, substantially increases risk of sepsis. Bacterial sepsis mostly due to gram positive organisms and fungal sepsis are observed in up to 80% and 30% patients, respectively.
sodium transport from inhibition of Na/K ATPase. Hypoglycaemia (due to depleted hepatic glycogen
store and hyperinsulinaemia
), hypokalaemia, hypophosphataemia and Metabolic alkalosis
are often present, independent of renal function. Lactic acidosis
occurs predominantly in paracetamol (also known as acetaminophen) overdose.
, 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 ALF cases, and is likely to contribute in haemodynamic compromise. 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.
Pulmonary complications occur in up to 50% of patients. Severe lung injury and hypoxemia
result in high mortality. Most cases of severe lung injury are due to ARDS, with or without sepsis
. Pulmonary haemorrhage, pleural effusion
s, atelectasis
, and intrapulmonary shunts also contribute to respiratory difficulty.
and there is any evidence of altered sensorium
, the diagnosis of ALF should be strongly suspected, and hospital admission is mandatory. Initial laboratory examination must be extensive in order to evaluate both the aetiology and severity.
Initial laboratory analysis
History taking should include careful review of possible exposures to viral infection and drugs or other toxins. From history and clinical examination, possibility of underlying chronic disease should be ruled out as it may require different management.
A liver biopsy
done via the transjugular route because of coagulopathy
is not usually necessary, other than in occasional malignancies. As the evaluation continues, several important decisions have to be made; such as whether to admit the patient to an ICU, or whether to transfer the patient to a transplant facility. Consultation with the transplant centre as early as possible is critical due to possibility of rapid progression of ALF.
Treatment involves admission to hospital. Often, intensive care unit
admission or very close observation is required. Supportive treatment is with adequate nutrition
, optimalisation of the fluid balance
, mechanical ventilation
and intracranial pressure
monitoring (in severe encephalopathy), and treatment aimed at removing the underlying cause (such as acetylcysteine for paracetamol poisoning). Other supportive measures may include the drainage of ascites
.
While many people who develop acute liver failure recover with supportive treatment, liver transplantation is often required in people who continue to deteriorate or have adverse prognostic
factors.
"Liver dialysis
" (various measures to replace normal liver function) is evolving as a treatment modality, and is gradually being introduced in the care of patients with liver failure.
Several prognostic scoring systems have been devised to predict mortality and to identify who will require early liver transplant. These include King's College Hospital criteria, MELD score
, APACHE II
, and Clichy criteria.
within 8 weeks of the appearance of the first symptoms and in the absence of pre-existing liver disease". Later, it was suggested that the term fulminant should be confined to patients who develop jaundice to encephalopathy within 2 weeks. Terms subfulminant hepatic failure and late onset hepatic failure were coined for onset between 2 weeks to 3 months and for 8 weeks to 24 weeks, respectively. The umbrella term of acute liver failure was proposed by King's College group, which has been adopted in this article. Paradoxically, in this classification, the best prognosis is in the hyperacute group.
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
), and indicates that the liver has sustained severe damage (loss of function of 80-90% of liver cells). The complications are hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy is the occurrence of confusion, altered level of consciousness and coma as a result of liver failure. In the advanced stages it is called hepatic coma or coma hepaticum...
and impaired protein synthesis (as measured by the levels of serum albumin
Serum albumin
Serum albumin, often referred to simply as albumin is a protein that in humans is encoded by the ALB gene.Serum albumin is the most abundant plasma protein in mammals. Albumin is essential for maintaining the osmotic pressure needed for proper distribution of body fluids between intravascular...
and the prothrombin time
Prothrombin time
The prothrombin time and its derived measures of prothrombin ratio and international normalized ratio are measures of the extrinsic pathway of coagulation. This test is also called "ProTime INR" and "INR PT". They are used to determine the clotting tendency of blood, in the measure of warfarin...
in the blood). The 1993 classification defines hyperacute as within 1 week, acute as 8–28 days and subacute as 4–12 weeks. It reflects the fact that the pace of disease evolution strongly influences prognosis. Underlying etiology
Etiology
Etiology is the study of causation, or origination. The word is derived from the Greek , aitiologia, "giving a reason for" ....
is the other significant determinant of outcome.
Causes
Common causes for acute liver failure are paracetamol (acetaminophen) overdoseParacetamol toxicity
Paracetamol toxicity is caused by excessive use or overdose of the analgesic drug paracetamol . Mainly causing liver injury, paracetamol toxicity is one of the most common causes of poisoning worldwide...
, idiosyncratic reaction to medication (e.g. tetracycline, troglitazone
Troglitazone
Troglitazone is an anti-diabetic and antiinflammatory drug, and a member of the drug class of the thiazolidinediones. It was developed by Daiichi Sankyo Co.. In the United States, it was introduced and manufactured by Parke-Davis in the late 1990s, but turned out to be associated with an...
), excessive alcohol intake
Alcoholic beverage
An alcoholic beverage is a drink containing ethanol, commonly known as alcohol. Alcoholic beverages are divided into three general classes: beers, wines, and spirits. They are legally consumed in most countries, and over 100 countries have laws regulating their production, sale, and consumption...
(severe alcoholic hepatitis
Alcoholic hepatitis
Alcoholic hepatitis is hepatitis due to excessive intake of alcohol. While distinct from cirrhosis, it is regarded as the earliest stage of alcoholic liver disease. Symptoms are jaundice, ascites , fatigue and hepatic encephalopathy...
), viral hepatitis (hepatitis A
Hepatitis A
Hepatitis A is an acute infectious disease of the liver caused by the hepatitis A virus , an RNA virus, usually spread the fecal-oral route; transmitted person-to-person by ingestion of contaminated food or water or through direct contact with an infectious person...
or B - it is extremely uncommon in hepatitis C
Hepatitis C
Hepatitis C is an infectious disease primarily affecting the liver, caused by the hepatitis C virus . The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years...
), acute fatty liver of pregnancy
Acute fatty liver of pregnancy
Acute fatty liver of pregnancy is a rare life-threatening complication of pregnancy that occurs in the third trimester or the immediate period after delivery. It is thought to be caused by a disordered metabolism of fatty acids by mitochondria in the mother, caused by deficiency in the LCHAD enzyme...
, and idiopathic (without an obvious cause). Reye syndrome is acute liver failure in a child with a viral infection (e.g. chickenpox
Chickenpox
Chickenpox or chicken pox is a highly contagious illness caused by primary infection with varicella zoster virus . It usually starts with vesicular skin rash mainly on the body and head rather than at the periphery and becomes itchy, raw pockmarks, which mostly heal without scarring...
); it appears that aspirin
Aspirin
Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...
use may play a significant role. Wilson's disease
Wilson's disease
Wilson's disease or hepatolenticular degeneration is an autosomal recessive genetic disorder in which copper accumulates in tissues; this manifests as neurological or psychiatric symptoms and liver disease...
(hereditary copper accumulation) may infrequently present with acute liver failure.
Pathology
In the majority of acute liver failure (ALF) there is widespread hepatocellular necrosis beginning in the centrizonal distributionHepatic lobule
A hepatic lobule is a small division of the liver defined at the histological scale. It should not be confused with the anatomic lobes of the liver , or any of the functional lobe classification systems....
and progressing towards portal tracts. The degree of parenchymal inflammation is variable and is proportional to duration of disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
.
Zone 1 (periportal) occurs in phosphorus poisoning or eclampsia.
Zone 2 (midzonal), although rare, is seen in yellow fever.
Zone 3 (centrilobular) occurs with ischemic injury, toxic effects, carbon tetrachloride exposure, or chloroform ingestion. Drugs such as acetaminophen may be metabolized in zone 1 to toxic compounds that cause necrosis on zone 3.
Cerebral edema and encephalopathy
In ALF, cerebral oedema leads to hepatic encephalopathyHepatic encephalopathy
Hepatic encephalopathy is the occurrence of confusion, altered level of consciousness and coma as a result of liver failure. In the advanced stages it is called hepatic coma or coma hepaticum...
, coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
, brain herniation
Brain herniation
Brain herniation, also known as cistern obliteration, is a deadly side effect of very high intracranial pressure that occurs when the brain shifts across structures within the skull...
and eventually death. Detection of encephalopathy is central to the diagnosis of ALF. It may vary from subtle deficit in higher brain function (e.g. mood, concentration in grade I) to deep coma (grade IV). Patients presenting as acute and hyperacute liver failure are at greater risk of developing cerebral oedema and grade IV encephalopathy. The pathogenesis
Pathogenesis
The pathogenesis of a disease is the mechanism by which the disease is caused. The term can also be used to describe the origin and development of the disease and whether it is acute, chronic or recurrent...
remains unclear but is likely to be a consequence of several phenomena. There is a build up of toxic substances like ammonia
Ammonia
Ammonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...
, mercaptan, endogenous benzodiazepines and serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
/tryptophan
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...
in the brain. This affects neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
level and neuroreceptor activation. Autoregulation of cerebral blood flow is impaired and is associated with anaerobic glycolysis
Anaerobic glycolysis
Anaerobic glycolysis is the transformation of glucose to pyruvate when limited amounts of oxygen are available. Anaerobic glycolysis is only an effective means of energy production during short, intense exercise, providing energy for a period ranging from 10 seconds to 2 minutes...
and oxidative stress
Oxidative stress
Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
. Neuronal cell astrocyte
Astrocyte
Astrocytes , also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord...
s are susceptible to these changes and they swell up, resulting in increased intracranial pressure. Inflammatory mediators also play important role.
Unfortunately, signs of elevated intracranial pressure
Intracranial pressure
Intracranial pressure is the pressure inside the skull and thus in the brain tissue and cerebrospinal fluid . The body has various mechanisms by which it keeps the ICP stable, with CSF pressures varying by about 1 mmHg in normal adults through shifts in production and absorption of CSF...
such as papilloedema and loss of pupillary reflexes are not reliable and occur late in the disease process. CT
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
imaging of the brain is also unhelpful in detecting early cerebral oedema but is often performed to rule out intra-cerebral bleeding
Intracranial hemorrhage
An intracranial hemorrhage is a hemorrhage, or bleeding, within the skull.-Causes:Intracranial bleeding occurs when a blood vessel within the skull is ruptured or leaks. It can result from physical trauma or nontraumatic causes such as a ruptured aneurysm...
. Invasive intracranial pressure monitoring via subdural
Dura mater
The dura mater , or dura, is the outermost of the three layers of the meninges surrounding the brain and spinal cord. It is derived from Mesoderm. The other two meningeal layers are the pia mater and the arachnoid mater. The dura surrounds the brain and the spinal cord and is responsible for...
route is often recommended, however the risk of complications must be weighed against the possible
benefit (1% fatal haemorrhage). The aim is to maintain intracranial pressures below 25 mmHg, cerebral perfusion pressures above 50 mm Hg.
Coagulopathy
CoagulopathyCoagulopathy
Coagulopathy is a condition in which the blood’s ability to clot is impaired. This condition can cause prolonged or excessive bleeding, which may occur spontaneously or following an injury or medical and dental procedures.The normal clotting process depends on the interplay of various proteins in...
is another cardinal feature of ALF. The Liver has the central role in synthesis of almost all coagulation factors and some inhibitors of coagulation
Coagulation
Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...
and fibrinolysis
Fibrinolysis
Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. This process has two types: primary fibrinolysis and secondary fibrinolysis...
. Hepatocellular necrosis
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
leads to impaired synthesis
Biosynthesis
Biosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...
of many coagulation factors and their inhibitors. The former produces a prolongation in Prothrombin time
Prothrombin time
The prothrombin time and its derived measures of prothrombin ratio and international normalized ratio are measures of the extrinsic pathway of coagulation. This test is also called "ProTime INR" and "INR PT". They are used to determine the clotting tendency of blood, in the measure of warfarin...
which is widely used to monitor severity of hepatic injury.There is significant platelet dysfunction (with both quantitative and qualitative platelet defects). Progressive thrombocytopenia
Thrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
with loss of larger and more active platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
is almost universal. Thrombocytopenia with or without DIC
Disseminated intravascular coagulation
Disseminated intravascular coagulation , also known as disseminated intravascular coagulopathy or consumptive coagulopathy, is a pathological activation of coagulation mechanisms that happens in response to a variety of diseases. DIC leads to the formation of small blood clots inside the blood...
increases risk of intracerebral bleeding.
Renal failure
Renal failureRenal failure
Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
is common, present in more than 50% of ALF patients, either due to original insult such as paracetamol resulting in acute tubular necrosis
Acute tubular necrosis
Acute tubular necrosis or is a medical condition involving the death of tubular cells that form the tubule that transports urine to the ureters while reabsorbing 99% of the water . Tubular cells continually replace themselves and if the cause of ATN is removed then recovery is likely...
or from hyperdynamic circulation
Hyperdynamic circulation
Hyperdynamic circulation is abnormally increased circulatory volume. Systemic vasodilation and the associated decrease in peripheral vascular resistance results in decreased pulmonary capillary wedge pressure and decreased blood pressure, often presenting with a collapsing pulse...
leading to hepatorenal syndrome
Hepatorenal syndrome
Hepatorenal syndrome is a life-threatening medical condition that consists of rapid deterioration in kidney function in individuals with cirrhosis or fulminant liver failure...
or functional renal failure. Because of impaired production of urea, blood urea does not represent degree of renal impairment.
Inflammation and infection
About 60% of all ALF patients fulfil the criteria for systemic inflammatory syndromeSystemic inflammatory response syndrome
Systemic inflammatory response syndrome is an inflammatory state affecting the whole body, frequently a response of the immune system to infection, but not necessarily so...
irrespective of presence or absence of infection. This often contributes towards multi organ failure
Multiple organ dysfunction syndrome
Multiple organ dysfunction syndrome ', previously known as multiple organ failure or multisystem organ failure , is altered organ function in an acutely ill patient requiring medical intervention to achieve homeostasis...
. Impaired host defence mechanism, due to impaired opsonisation, chemotaxis
Chemotaxis
Chemotaxis is the phenomenon in which somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. This is important for bacteria to find food by swimming towards the highest concentration of food molecules,...
and intracellular killing, substantially increases risk of sepsis. Bacterial sepsis mostly due to gram positive organisms and fungal sepsis are observed in up to 80% and 30% patients, respectively.
Metabolic derangements
Hyponatraemia is an almost universal finding due to water retention and a shift in intracellularIntracellular
Not to be confused with intercellular, meaning "between cells".In cell biology, molecular biology and related fields, the word intracellular means "inside the cell".It is used in contrast to extracellular...
sodium transport from inhibition of Na/K ATPase. Hypoglycaemia (due to depleted hepatic glycogen
Glycogen
Glycogen is a molecule that serves as the secondary long-term energy storage in animal and fungal cells, with the primary energy stores being held in adipose tissue...
store and hyperinsulinaemia
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
), hypokalaemia, hypophosphataemia and Metabolic alkalosis
Metabolic alkalosis
Metabolic alkalosis is a metabolic condition in which the pH of tissue is elevated beyond the normal range . This is the result of decreased hydrogen ion concentration, leading to increased bicarbonate, or alternatively a direct result of increased bicarbonate concentrations.-Terminology:*Alkalosis...
are often present, independent of renal function. Lactic acidosis
Lactic acidosis
Lactic acidosis is a physiological condition characterized by low pH in body tissues and blood accompanied by the buildup of lactate especially D-lactate, and is considered a distinct form of metabolic acidosis. The condition typically occurs when cells receive too little oxygen , for example...
occurs predominantly in paracetamol (also known as acetaminophen) overdose.
Haemodynamic and cardio-respiratory compromise
Hyperdynamic circulationHyperdynamic circulation
Hyperdynamic circulation is abnormally increased circulatory volume. Systemic vasodilation and the associated decrease in peripheral vascular resistance results in decreased pulmonary capillary wedge pressure and decreased blood pressure, often presenting with a collapsing pulse...
, with peripheral vasodilatation from low systemic vascular resistance, leads to hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
. There is a compensatory increase in cardiac output
Cardiac output
Cardiac output is the volume of blood being pumped by the heart, in particular by a left or right ventricle in the time interval of one minute. CO may be measured in many ways, for example dm3/min...
. Adrenal insufficiency
Adrenal insufficiency
Adrenal insufficiency is a condition in which the adrenal glands, located above the kidneys, do not produce adequate amounts of steroid hormones , primarily cortisol, but may also include impaired aldosterone production which regulates sodium, potassium and water retention...
has been documented in 60% of ALF cases, and is likely to contribute in haemodynamic compromise. There is also abnormal oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
transport and utilization. Although delivery of oxygen to the tissues is adequate, there is a decrease in tissue oxygen uptake, resulting in tissue
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
hypoxia
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
and lactic acidosis.
Pulmonary complications occur in up to 50% of patients. Severe lung injury and hypoxemia
Hypoxemia
Hypoxemia is generally defined as decreased partial pressure of oxygen in blood, sometimes specifically as less than or causing hemoglobin oxygen saturation of less than 90%.-Distinction from anemia and hypoxia:...
result in high mortality. Most cases of severe lung injury are due to ARDS, with or without sepsis
Sepsis
Sepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...
. Pulmonary haemorrhage, pleural effusion
Pleural effusion
Pleural effusion is excess fluid that accumulates between the two pleural layers, the fluid-filled space that surrounds the lungs. Excessive amounts of such fluid can impair breathing by limiting the expansion of the lungs during ventilation.-Pathophysiology:...
s, atelectasis
Atelectasis
Atelectasis is defined as the collapse or closure of alveoli resulting in reduced or absent gas exchange. It may affect part or all of one lung. It is a condition where the alveoli are deflated, as distinct from pulmonary consolidation.It is a very common finding in chest x-rays and other...
, and intrapulmonary shunts also contribute to respiratory difficulty.
ALF in late pregnancy
In late pregnancy liver function decreases significantly, which can be easily monitored by blood tests. Early clinical manifestations of ALF in late pregnancy include: hypodynamia, decrease in appetite, dark amber urine, deep jaundice, nausea, vomiting, and abdominal distention. Among patients whose deaths were attributed to ALF in late pregnancy, the majority had experienced vaginal deliveries.Evaluation
All patients with clinical or laboratory evidence of moderate to severe acute hepatitis should have immediate measurement of prothrombin time and careful evaluation of mental status. If the prothrombin time is prolonged by ≈ 4–6 seconds or more (INR ≥1.5),and there is any evidence of altered sensorium
Sensorium
The term sensorium refers to the sum of an organism's perception, the "seat of sensation" where it experiences and interprets the environments within which it lives. The term originally enters English from the Late Latin in the mid-17th century, from the stem sens-...
, the diagnosis of ALF should be strongly suspected, and hospital admission is mandatory. Initial laboratory examination must be extensive in order to evaluate both the aetiology and severity.
Initial laboratory analysis
- Prothrombin timeProthrombin timeThe prothrombin time and its derived measures of prothrombin ratio and international normalized ratio are measures of the extrinsic pathway of coagulation. This test is also called "ProTime INR" and "INR PT". They are used to determine the clotting tendency of blood, in the measure of warfarin...
/INR - Complete blood countComplete blood countA complete blood count , also known as full blood count or full blood exam or blood panel, is a test panel requested by a doctor or other medical professional that gives information about the cells in a patient's blood...
- Chemistries
- Liver function test: ASTAspartate transaminaseAspartate transaminase , also called aspartate aminotransferase or serum glutamic oxaloacetic transaminase , is a pyridoxal phosphate -dependent transaminase enzyme . AST catalyzes the reversible transfer of an α-amino group between aspartate and glutamate and, as such, is an important enzyme in...
, ALTAlanine transaminaseAlanine transaminase or ALT is a transaminase enzyme . It is also called serum glutamic pyruvic transaminase or alanine aminotransferase ....
, alkaline phosphataseAlkaline phosphataseAlkaline phosphatase is a hydrolase enzyme responsible for removing phosphate groups from many types of molecules, including nucleotides, proteins, and alkaloids. The process of removing the phosphate group is called dephosphorylation...
, GGT, total bilirubinBilirubinBilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...
, albuminAlbuminAlbumin refers generally to any protein that is water soluble, which is moderately soluble in concentrated salt solutions, and experiences heat denaturation. They are commonly found in blood plasma, and are unique to other blood proteins in that they are not glycosylated... - CreatinineCreatinineCreatinine is a break-down product of creatine phosphate in muscle, and is usually produced at a fairly constant rate by the body...
, urea/blood urea nitrogenBlood urea nitrogenThe blood urea nitrogen test is a measure of the amount of nitrogen in the blood in the form of urea, and a measurement of renal function. Urea is a by- product from metabolism of proteins by the liver and is removed from the blood by the kidneys.-Physiology:The liver produces urea in the urea...
, sodium, potassium, chloride, bicarbonate, calcium, magnesium, phosphate - glucoseBlood sugarThe blood sugar concentration or blood glucose level is the amount of glucose present in the blood of a human or animal. Normally in mammals, the body maintains the blood glucose level at a reference range between about 3.6 and 5.8 mM , or 64.8 and 104.4 mg/dL...
- AmylaseAmylaseAmylase is an enzyme that catalyses the breakdown of starch into sugars. Amylase is present in human saliva, where it begins the chemical process of digestion. Food that contains much starch but little sugar, such as rice and potato, taste slightly sweet as they are chewed because amylase turns...
and lipaseLipaseA lipase is an enzyme that catalyzes the formation or cleavage of fats . Lipases are a subclass of the esterases.Lipases perform essential roles in the digestion, transport and processing of dietary lipids in most, if not all, living organisms...
- Liver function test: AST
- Arterial blood gasArterial blood gasAn arterial blood gas is a blood test that is performed using blood from an artery. It involves puncturing an artery with a thin needle and syringe and drawing a small volume of blood. The most common puncture site is the radial artery at the wrist, but sometimes the femoral artery in the groin or...
, lactateLactic acidLactic acid, also known as milk acid, is a chemical compound that plays a role in various biochemical processes and was first isolated in 1780 by the Swedish chemist Carl Wilhelm Scheele. Lactic acid is a carboxylic acid with the chemical formula C3H6O3... - Blood type and screen
- ParacetamolParacetamolParacetamol INN , or acetaminophen USAN , is a widely used over-the-counter analgesic and antipyretic . It is commonly used for the relief of headaches and other minor aches and pains and is a major ingredient in numerous cold and flu remedies...
(Acetaminophen) level, Toxicology screen - Viral hepatitisViral hepatitisViral hepatitis is liver inflammation due to a viral infection. It may present in acute or chronic forms. The most common causes of viral hepatitis are the five unrelated hepatotropic viruses Hepatitis A, Hepatitis B, Hepatitis C, Hepatitis D, and Hepatitis E...
serologies: anti-HAV IgM, HBSAg, anti-HBc IgM, anti-HEV - Autoimmune markers: ANAAnti-nuclear antibodyAnti-nuclear antibodies are autoantibodies directed against contents of the cell nucleus....
, ASMAAnti-smooth muscle antibodyAnti-smooth muscle antibodies are antibodies formed against smooth muscle. These antibodies are typically associated with autoimmune hepatitis.These antibodies can be directed against actin, troponin, and tropomyosin....
, LKMA, ImmunoglobulinAntibodyAn antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
levels - CeruloplasminCeruloplasminCeruloplasmin is a ferroxidase enzyme that in humans is encoded by the CP gene.Ceruloplasmin is the major copper-carrying protein in the blood, and in addition plays a role in iron metabolism. It was first described in 1948...
Level ( when Wilson's disease suspected) - Pregnancy testPregnancy testA pregnancy test attempts to determine whether or not a woman is pregnant.These markers are found in urine and blood, and pregnancy tests require sampling one of these substances. The first of these markers to be discovered, human chorionic gonadotropin , was discovered in 1930 to be produced by...
(females) - AmmoniaAmmoniaAmmonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...
(arterial if possible) - HIVHIVHuman immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
status (has implication for transplantationOrgan transplantOrgan transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...
)
History taking should include careful review of possible exposures to viral infection and drugs or other toxins. From history and clinical examination, possibility of underlying chronic disease should be ruled out as it may require different management.
A liver biopsy
Liver biopsy
Liver biopsy is the biopsy from the liver. It is a medical test that is done to aid diagnosis of liver disease, to assess the severity of known liver disease, and to monitor the progress of treatment.-History:...
done via the transjugular route because of coagulopathy
Coagulopathy
Coagulopathy is a condition in which the blood’s ability to clot is impaired. This condition can cause prolonged or excessive bleeding, which may occur spontaneously or following an injury or medical and dental procedures.The normal clotting process depends on the interplay of various proteins in...
is not usually necessary, other than in occasional malignancies. As the evaluation continues, several important decisions have to be made; such as whether to admit the patient to an ICU, or whether to transfer the patient to a transplant facility. Consultation with the transplant centre as early as possible is critical due to possibility of rapid progression of ALF.
Treatment
| King's College Hospital criteria for liver transplantation in acute liver failure |
| Patients with paracetamol Paracetamol Paracetamol INN , or acetaminophen USAN , is a widely used over-the-counter analgesic and antipyretic . It is commonly used for the relief of headaches and other minor aches and pains and is a major ingredient in numerous cold and flu remedies... toxicity pH <7.3 or Prothrombin time Prothrombin time The prothrombin time and its derived measures of prothrombin ratio and international normalized ratio are measures of the extrinsic pathway of coagulation. This test is also called "ProTime INR" and "INR PT". They are used to determine the clotting tendency of blood, in the measure of warfarin... >100 seconds and serum creatinine level >3.4 mg/dL (>300 μmol/l) if in grade III or IV encephalopathy Hepatic encephalopathy Hepatic encephalopathy is the occurrence of confusion, altered level of consciousness and coma as a result of liver failure. In the advanced stages it is called hepatic coma or coma hepaticum... |
| Other patients Prothrombin time >100 seconds or Three of the following variables:
|
Treatment involves admission to hospital. Often, intensive care unit
Intensive Care Unit
thumb|220px|ICU roomAn intensive-care unit , critical-care unit , intensive-therapy unit/intensive-treatment unit is a specialized department in a hospital that provides intensive-care medicine...
admission or very close observation is required. Supportive treatment is with adequate nutrition
Nutrition
Nutrition is the provision, to cells and organisms, of the materials necessary to support life. Many common health problems can be prevented or alleviated with a healthy diet....
, optimalisation of the fluid balance
Fluid balance
Fluid balance is the concept of human homeostasis that the amount of fluid lost from the body is equal to the amount of fluid taken in. Euvolemia is the state of normal body fluid volume. Water is necessary for all life on Earth...
, mechanical ventilation
Mechanical ventilation
In medicine, mechanical ventilation is a method to mechanically assist or replace spontaneous breathing. This may involve a machine called a ventilator or the breathing may be assisted by a physician, respiratory therapist or other suitable person compressing a bag or set of bellows...
and intracranial pressure
Intracranial pressure
Intracranial pressure is the pressure inside the skull and thus in the brain tissue and cerebrospinal fluid . The body has various mechanisms by which it keeps the ICP stable, with CSF pressures varying by about 1 mmHg in normal adults through shifts in production and absorption of CSF...
monitoring (in severe encephalopathy), and treatment aimed at removing the underlying cause (such as acetylcysteine for paracetamol poisoning). Other supportive measures may include the drainage of ascites
Ascites
Ascites is a gastroenterological term for an accumulation of fluid in the peritoneal cavity.The medical condition is also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more archaically as abdominal dropsy. Although most commonly due to cirrhosis and severe liver...
.
While many people who develop acute liver failure recover with supportive treatment, liver transplantation is often required in people who continue to deteriorate or have adverse prognostic
Prognosis
Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...
factors.
"Liver dialysis
Liver dialysis
Liver dialysis is a detoxification treatment for liver failure and has shown promise for patients with hepatorenal syndrome. It is similar to hemodialysis and based on the same principles...
" (various measures to replace normal liver function) is evolving as a treatment modality, and is gradually being introduced in the care of patients with liver failure.
Acetylcysteine
Intravenous N-acetylcysteine has been found to be beneficial in both acetaminophen toxicity and non-acetaminophen-related acute liver failure.Prognosis
Historically mortality has been unacceptably high, being in excess of 80%. 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%.Several prognostic scoring systems have been devised to predict mortality and to identify who will require early liver transplant. These include King's College Hospital criteria, MELD score
Model for End-Stage Liver Disease
The Model for End-Stage Liver Disease, or MELD, is a scoring system for assessing the severity of chronic liver disease. It was initially developed to predict death within three months of surgery in patients who had undergone a transjugular intrahepatic portosystemic shunt procedure, and was...
, APACHE II
APACHE II
APACHE II is a severity-of-disease classification system , one of several ICU scoring systems...
, and Clichy criteria.
Terminology
To date, no universally accepted nomenclature has been adopted. Trey and Davidson introduced the term fulminant hepatic failure in 1970, which they described as a "...potentially reversible condition, the consequence of severe liver injury, with an onset of encephalopathyHepatic encephalopathy
Hepatic encephalopathy is the occurrence of confusion, altered level of consciousness and coma as a result of liver failure. In the advanced stages it is called hepatic coma or coma hepaticum...
within 8 weeks of the appearance of the first symptoms and in the absence of pre-existing liver disease". Later, it was suggested that the term fulminant should be confined to patients who develop jaundice to encephalopathy within 2 weeks. Terms subfulminant hepatic failure and late onset hepatic failure were coined for onset between 2 weeks to 3 months and for 8 weeks to 24 weeks, respectively. The umbrella term of acute liver failure was proposed by King's College group, which has been adopted in this article. Paradoxically, in this classification, the best prognosis is in the hyperacute group.