3. Tools used to assess hepatic encephalopathy by the included studies.

	Description	Advantages	Disadvantages
Asterixis Severity Scale (Williams 2000)	Format: clinical grading score Approximate time required: 1 minute Grades the severity of asterixis Grade 0: no tremor Grade 1: rare flapping motions Grade 2: occasional, irregular flaps Grade 3: frequent flaps Grade 4: almost continuous flapping motions	Quick and easy to perform Requires no additional resources	Prone to inter‐ and intra‐observer variability Crude method of detecting hepatic encephalopathy Not entirely specific to hepatic encephalopathy
Blood ammonia	Format: a blood test, taken either as an arterial or venous sample, to measure the level of ammonia Approximate time required: 5 minutes, although time to results can vary	Relatively quick to take sample Objective measure Requires little participant cooperation Resistant to confounding (such as age and education)	Level of ammonia has poor correlation with severity of hepatic encephalopathy in people with cirrhosis Logistically difficult to measure, as requires transportation on ice Potential differences between arterial and venous sampling
Clinical Hepatic Encephalopathy Staging Scale (CHESS) (Ortiz 2007)	Format: a set of 9 questions that the observer must answer. It is graded on a scale from 0 to 9, designed to reduce interobserver variability Approximate time required: 10 minutes Domains tested Orientation Attention Language Consciousness	Reflects the spectral nature of hepatic encephalopathy Shows good consistency and reproducibility	Not widely used apart from in clinical trials Needs further validation
Critical Flicker Frequency (CFF) (Kircheis 2002)	Format: participants look into a viewing chamber at a flashing light, the frequency of which steadily increases or decreases. The flicker frequency is the frequency at which the continuous‐appearing light begins to flicker as the frequency decreases. Approximate time required: 20 minutes	Widely accepted to involve the central nervous system Discriminatory between overt hepatic encephalopathy and unimpaired people Sensitive, simple, and reliable tool Low confounding, for example, by level of education	May be less useful in colour‐blind participants Instructions may be difficult to understand Age and aetiology of cirrhosis may confound results Not widely available
Electroencephalogram	Format: a neurophysiological test, providing a record of the brain's electric activity by placing electrodes over the surface of the scalp Approximate time required: 30 minutes People with hepatic encephalopathy may elicit slowing of normal higher frequencies, with bursts of activity in the low‐frequency theta and delta ranges	Objective measure of brain function Little participant cooperation required Resistant to confounding (such as age and education) Can be analysed spectrally	Non‐specific Less widely validated than other tests Variable availability Can be expensive Visual analysis can introduce inter‐ and intra‐observer variability
Inhibitory Control Test (ICT) (Bajaj 2007)	Format: a computer‐based programme, showing a series of random letters which participants should either respond to (targets), or not respond to (lures). Approximate time required: 20 minutes Domains tested Attention Response inhibition	High sensitivity Good concordance with other tests	Time‐consuming Difficult to understand test instructions Subject to a learning effect Influenced by population demographics
Portal‐Systemic Encephalopathy Sum (PSE Sum) and Index (PSE Index) (Conn 1977)	Provides an index of the severity of hepatic encephalopathy by adding scores for the degree of abnormality, expressed on a 0 to 4+ scale, for: Mental status assessed using West Haven Criteria Asterixis Number Connection Test A time Blood ammonia concentration EEG mean cycle frequency Each component is arbitrarily weighted in proportion to its importance: mental state is weighted by a factor of 3, whilst other variables are assigned a factor of 1. The PSE Sum is the total of the weighted scores; its maximum possible value is 28. The PSE index is the ratio of the estimated PSE Sum to the maximum possible. Approximate time required: dependent on the time taken to obtain the results of the blood ammonia and EEG	Comprehensive score Use of the PSE Index takes account of the eventuality that information on one or more of the components of the PSE Sum may not be available at every time point.	Time‐consuming EEG is often not readily available
Psychometric Hepatic Encephalopathy Score (PHES) (Weissenborn 2001)	Format: a battery of five pencil‐and‐paper tests Approximate time required: 20 minutes Domains tested Psychomotor speed Precision Visual perception Visuospatial orientation Visual construction Concentration Attention Memory Tests include the number connection tests A and B, digit‐symbol test, line tracing test and serial dotting test. Figure connection tests may be used in illiterate people. Some studies in this review have used specific tests from this battery, but not the entire battery. A normalised 'z‐score' can be calculated, and thresholds for the diagnosis of hepatic encephalopathy vary by country and population.	Validated in several populations internationally High diagnostic sensitivity and specificity Multiple versions available to allow for repeated testing Specifically designed to detect subtle cognitive changes in people with minimal hepatic encephalopathy	Poor test of memory Difficult to interpret and score Relies on fine motor skills Can be time‐consuming Unpopular in countries such as the USA due to lack of normative data and availability
Reitan Test (Reitan 1955)	Format: a pencil‐and‐paper trail making test, where participants must connect a series of circles in ascending order Approximate time required: 10 minutes Domains tested Psychomotor speed Visual perception Visuospatial orientation Concentration	Short to conduct Inexpensive Easily administered to participants	Poor test of memory Difficult to interpret and score Relies on fine motor skills Largely replaced by the number connection test
Stroop Test (EncephalApp) (Bajaj 2013)	Format: a smartphone‐based test, where participants must respond to the matching colour of a stimulus, presented as either hash signs (###; 'stroop off'), or as a distractor word (for example, 'blue'; 'stroop on'). Approximate time required: 5 to 10 minutes Domains tested Psychomotor speed Cognitive flexibility Reaction time interference	Simple to administer Portable Quick to conduct	Only a modest specificity Not suitable for people with colour blindness
Wechsler Adult Intelligence Scale (WAIS) (Lawton 1939)	Format: an IQ test, of varying iterations, formed of multiple tests, split into verbal IQ and performance IQ: Vocabulary Similarities Information Comprehension Arithmetic Digits Span Letter‐Number Sequencing Picture Completion Block Design Matrix Reasoning Digit Symbol Symbol Search Approximate time required: 60 to 85 minutes Domains tested Verbal comprehension Working memory Perceptual organisation Processing speed Abstract reasoning Semantic knowledge Visual motor construction Visual spatial processing Attention	Comprehensive neurocognitive assessment Standardised score in the United States and Canada	Not specific to hepatic encephalopathy Time‐consuming Prone to confounding, for example by age and education
West‐Haven Criteria/Conn Score (Conn 1977)	Format: clinical grading score Approximate time required: < 5 minutes Grades the severity of hepatic encephalopathy into 4 main categories Minimal: abnormal results on psychometric or neurophysiological testing without clinical manifestations Grade I: changes in behaviour, mild confusion, slurred speech, impaired sleep, shortened attention span Grade II: lethargy, moderate confusion, apathy, subtle personality change and inappropriate behaviour Grade III: marked confusion, incoherent speech, somnolence to semi‐stupor but remains responsive to verbal stimuli, gross disorientation Grade IV: coma	Simple and quick to conduct Widely used and recognised classification	Prone to inter‐observer variation at less severe grades

IQ: intelligence quotient