The King's College Criteria or the King's College Hospital criteria were devised in 1989 to determine if there were any early indices of poor prognosis in patients with

acute liver failure Acute liver failure is the appearance of severe complications rapidly after the first signs (such as jaundice) of liver disease, and indicates that the liver has sustained severe damage (loss of function of 80–90% of liver cells). The complicati ...

. Acute liver failure is defined as the onset of

encephalopathy Encephalopathy (; from grc, ἐνκέφαλος "brain" + πάθος "suffering") means any disorder or disease of the brain, especially chronic degenerative conditions. In modern usage, encephalopathy does not refer to a single disease, but r ...

(altered mental status) or

coagulopathy Coagulopathy (also called a bleeding disorder) is a condition in which the blood's ability to coagulate (form clots) is impaired. This condition can cause a tendency toward prolonged or excessive bleeding (bleeding diathesis), which may occur spo ...

(altered bleeding tendencies) within 26 weeks of a patient diagnosed with liver disease. Patients with

hepatitis B Hepatitis B is an infectious disease caused by the ''Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. Fo ...

acquired at birth,

Wilson's disease Wilson's disease is a genetic disorder in which excess copper builds up in the body. Symptoms are typically related to the brain and liver. Liver-related symptoms include vomiting, weakness, fluid build up in the abdomen, swelling of the legs, ...

and

autoimmune hepatitis Autoimmune hepatitis, formerly known as lupoid hepatitis, plasma cell hepatitis, or autoimmune chronic active hepatitis, is a chronic, autoimmune disease of the liver that occurs when the body's immune system attacks liver cells, causing the liv ...

are included if their disease was identified within the past 26 weeks. These patients are very ill, and have a very high risk of dying of their illness without adequate treatment which may include

liver transplantation Liver transplantation or hepatic transplantation is the replacement of a diseased liver with the healthy liver from another person (allograft). Liver transplantation is a treatment option for end-stage liver disease and acute liver failure, al ...

. It is important that physicians find ways of identifying patients with acute liver failure early in their course who will do poorly, and may require liver transplantation. The King's College Criteria have consistently shown excellent operating characteristics for determining prognosis in these patients. As

becomes a more accessible option for patients with acute liver failure, the King's College Criteria serve a role in determining which patients may require transplantation.

Criteria

The King's College criteria were described in a seminal publication in 1989 by J.G. O'Grady and colleagues from King's College School of Medicine. 588 patients with acute liver failure who presented to King's College Hospital from 1973 to 1985 were assessed retrospectively to determine if there were particular clinical features or tests that correlated poorly with prognosis. The criteria were stratified into acetaminophen and non-acetaminophen causes of acute liver failure, due to the different operating characteristics of parameters correlating with prognosis in the two causes.

Paracetamol induced acute liver failure

Acetaminophen Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol. At a standard dose, paracetamol only slightly decreases body temperature; it is inferior ...

(or

paracetamol Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol. At a standard dose, paracetamol only slightly decreases body temperature; it is inferior ...

) is an

analgesic An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...

medication that can affect the liver when administered in high doses. Acetaminophen is predominantly conjugated into

glucuronate Glucuronic acid (from Greek γλεῦκος "''wine, must''" and οὖρον "''urine''") is a uronic acid that was first isolated from urine (hence the name). It is found in many gums such as gum arabic (c. 18%), xanthan, and kombucha tea and ...

and

sulfate The sulfate or sulphate ion is a polyatomic anion with the empirical formula . Salts, acid derivatives, and peroxides of sulfate are widely used in industry. Sulfates occur widely in everyday life. Sulfates are salts of sulfuric acid and many ar ...

moieties by

Phase II metabolism Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism (from the Greek xenos "stranger" and biotic "related to living beings") is the set of ...

. A small percentage is metabolized by the

cytochrome P450 Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...

pathway to a toxic metabolite, NAPQI. NAPQI is conjugated by

glutathione Glutathione (GSH, ) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, pero ...

to non-toxic cysteine and mercapturic acid moieties. In cases of acetaminophen toxicity, the Phase II conjugation enzymes are saturated, and a higher fraction is converted to NAPQI. The conjugation of NAPQI to glutathione occurs until glutathione is depleted from hepatic reserves, after which the toxic NAPQI accumulates and causes damage to the hepatocytes. This occurs primarily in areas of the liver that are relatively poorly perfused with oxygen, or furthest away from the

hepatic artery The common hepatic artery is a short blood vessel that supplies oxygenated blood to the liver, pylorus of the stomach, duodenum, pancreas, and gallbladder. It arises from the celiac artery and has the following branches: Additional images ...

, termed ''Zone 3''. Acetaminophen overdose is associated with Zone 3 necrosis, to the point that acute liver failure may result. The King's College Criteria identify two groups of patients that have a poor prognosis with acetaminophen induced liver failure: * Arterial pH < 7.3 (taken by sampling of blood from an artery); or, * All three of an

international normalized ratio The prothrombin time (PT) – along with its derived measures of prothrombin ratio (PR) and international normalized ratio (INR) – is an assay for evaluating the ''extrinsic'' pathway and common pathway of coagulation. This blood test is als ...

(INR) of greater than 6.5,

serum creatinine Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass). Biological relevance Serum creatinine (a blood measurement) is an import ...

of greater than 300 micromoles per litre and the presence of encephalopathy (of grade III or IV). These three are markers of

kidney function Assessment of kidney function occurs in different ways, using the presence of symptoms and signs, as well as measurements using urine tests, blood tests, and medical imaging. Functions of a healthy kidney include maintaining a person's fluid ...

and mental status.

Non-paracetamol acute liver failure

There are many causes of acute liver failure aside from acetaminophen toxicity; these include viral hepatitis—including

hepatitis A Hepatitis A is an infectious disease of the liver caused by ''Hepatovirus A'' (HAV); it is a type of viral hepatitis. Many cases have few or no symptoms, especially in the young. The time between infection and symptoms, in those who develop them ...

(rarely),

hepatitis C Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, a ...

(rarely),

hepatitis E Hepatitis E is inflammation of the liver caused by infection with the hepatitis E virus (HEV); it is a type of viral hepatitis. Hepatitis E has mainly a fecal-oral transmission route that is similar to hepatitis A, although the viruses are unrel ...

(especially in pregnant women),

Epstein–Barr virus The Epstein–Barr virus (EBV), formally called ''Human gammaherpesvirus 4'', is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus. It is b ...

cytomegalovirus ''Cytomegalovirus'' (''CMV'') (from ''cyto-'' 'cell' via Greek - 'container' + 'big, megalo-' + -''virus'' via Latin 'poison') is a genus of viruses in the order ''Herpesvirales'', in the family ''Herpesviridae'', in the subfamily ''Betaherpe ...

and

varicella zoster virus Varicella-zoster virus (VZV), also known as human herpesvirus 3 (HHV-3, HHV3) or ''Human alphaherpesvirus 3'' (taxonomically), is one of nine known herpes viruses that can infect humans. It causes chickenpox (varicella) commonly affecting chil ...

, the toxin of the

death cap ''Amanita phalloides'' (), commonly known as the death cap, is a deadly poisonous basidiomycete fungus, one of many in the genus ''Amanita''. Widely distributed across Europe, but now sprouting in other parts of the world, ''A. phalloides ...

mushroom (''Amanita phalloides''),

alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...

Budd–Chiari syndrome Budd–Chiari syndrome is a very rare condition, affecting one in a million adults. The condition is caused by occlusion of the hepatic veins that drain the liver. It presents with the classical triad of abdominal pain, ascites, and liver enlarge ...

, other medications (including

halothane Halothane, sold under the brand name Fluothane among others, is a general anaesthetic. It can be used to induce or maintain anaesthesia. One of its benefits is that it does not increase the production of saliva, which can be particularly useful i ...

hormonal contraception Hormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The origin ...

, and

isoniazid Isoniazid, also known as isonicotinic acid hydrazide (INH), is an antibiotic used for the treatment of tuberculosis. For active tuberculosis it is often used together with rifampicin, pyrazinamide, and either streptomycin or ethambutol. For l ...

), recreational drugs (including

ecstasy Ecstasy may refer to: * Ecstasy (emotion), a trance or trance-like state in which a person transcends normal consciousness * Religious ecstasy, a state of consciousness, visions or absolute euphoria * Ecstasy (philosophy), to be or stand outside o ...

br>
and, rarely, tumours infiltrating the liver. In patients with non-acetaminophen acute liver failure, the following criteria were identified as being associated with a poor prognosis: * INR greater than 6.5; or, * Three of the following five criteria: ** Patient age of less than 11 or greater than 40; ** Serum

bilirubin Bilirubin (BR) (Latin for "red bile") is a red-orange compound that occurs in the normal catabolic pathway that breaks down heme in vertebrates. This catabolism is a necessary process in the body's clearance of waste products that arise from the ...

of greater than 300 micromoles per litre; ** Time from onset of

jaundice Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...

to the development of

coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...

of greater than seven days; ** INR greater than 3.5; or, ** Drug toxicity, regardless of whether it was the cause of the acute liver failure.

Utility in prediction

The utility of the criteria in determining the prognosis of patients with acute liver failure is defined by their operating characteristics. The

positive predictive value The positive and negative predictive values (PPV and NPV respectively) are the proportions of positive and negative results in statistics and diagnostic tests that are true positive and true negative results, respectively. The PPV and NPV descr ...

of the criteria in predicting death from acute liver failure has ranged from 70% to 100%. A Canadian

meta-analysis A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting me ...

assessing various prognostic indices found that the specificity of the King's College criteria in predicting

mortality Mortality is the state of being mortal, or susceptible to death; the opposite of immortality. Mortality may also refer to: * Fish mortality, a parameter used in fisheries population dynamics to account for the loss of fish in a fish stock throug ...

exceeded 90%, with a sensitivity of 69%. As a result, the American Society for Study of Liver Diseases has recommended the King's College Criteria as being helpful early parameters in ascertaining the need for

in patients with acute liver failure.

Alternatives

A variety of other calculations have been done based on similar parameters to determine the risk of mortality in acute liver failure. The Acute Physiology and Chronic Health Evaluation II (

APACHE II APACHE II ("Acute Physiology and Chronic Health Evaluation II") is a severity-of-disease classification system, one of several ICU scoring systems. It is applied within 24 hours of admission of a patient to an intensive care unit (ICU): an int ...

) score has a comparable sensitivity to the King's College Criteria in determining prognosis.

References

{{reflist Gastroenterology