Hepatic encephalopathy is a major complication of cirrhosis. It is characterized by neuropsychiatric manifestations. In minimal hepatic encephalopathy (MHE), patients have alterations in sleep pattern, and there is difficulty in performing even day-to-day routine activities like driving a vehicle, doing simple calculations, and so forth [
The diagnosis of minimal hepatic encephalopathy (MHE) is made using a battery of neuropsychometric or neurophysiological tests [
We designed a test that would examine the three important domains—cognition, memory, and psychomotor skills—and used this test in patients with chronic liver disease to detect MHE.
The impaired domains of mental function in MHE have an impact on the quality of daily life [
In order to design the specific tasks which make up the MALT, a questionnaire investigating the specific daily mental demands encountered by the target population was administered to 100 individuals attending the out-patient liver clinic of Institute of Gastroenterology and Hepatology, Stanley Hospital, Chennai, India. Except for 5 patients who were either professionals or businessmen, the rest belonged to lower socioeconomic status and were laborers, unskilled workers, or farmers (Kuppuswamy’s socioeconomic status scale) [
For
All the three tests were designed using a colorful board, set of printed question cards, plastic building blocks, animal models, an audio device, and an instruction
These tasks were grouped into three different sections: Section 1: figure the field, Section 2: home sweet home, Section 3: road not taken.
Section 1 included steps like identification of animals and vegetables on the countryside/neighborhood, and identification of well-known sequences of events like sowing seeds, transplanting the saplings, harvesting, and finally transporting to the city. In this section, we also asked the patient to build a wall using blocks. The failure to perform this task was considered a sign of psycho-motor impairment.
Section 2 included steps like remembering the arrangement of things on the shelves at home and ability to narrate the steps of a task performed at home daily, such as washing a cloth or making tea. Impairment in memory and organization reflected directly on the performance in these steps. In the same section we tested the ability of the patient to identify and remember sounds by using different stimuli, such as a church bell or an ambulance siren. Examinees were also asked to cut paper using a pair of scissors, a measure of psychomotor abilities.
Section 3 included tasks that tested the numerical abilities of the patient (like we asked the patient to perform small transactions at the shop) and tasks that asked them to identify places that they may visit on a daily basis, like a temple, a water pump, or a market place. Short term memory was tested by asking the patient to recall the short list of things to buy from the shop that was narrated to him in Section 2. We included a test analogous to the trail tracing test in Section 3 where the patient had to negotiate a narrow path from the shop back to home, using his index finger along the trail. Performance on this step can be impaired in patients with psycho-motor impairment.
Two other tests were performed on the MALT board, which could affect the daily activities in MHE. These included (a) divided attention: ability to observe images on the board that were not included as a part of the task; (b) judgment ability: to select the shortest of the three shown paths. Table
MALT-steps summary.
Section | Task | Corresponding mental function |
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(1) Figure the field | Copy the figures | Visuospatial abilities |
Group similar objects | Recognition | |
Trace the sequence | Executive function | |
Name the animals | Naming | |
Build the wall | Constructional ability | |
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(2) Home sweet home | Complete the task | Executive function |
Remember the arrangement | Immediate visual memory | |
Cut along the line | Psychomotor skills | |
Recall the steps | Attention | |
Identify the sound | Auditory recall | |
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(3) The road not taken | Trace the path | Psycho-motor skills |
What from shop? | Delayed visual recall | |
How much to pay? | Calculation | |
Choose the shortest path. | Decision making | |
Quiz | Divided attention | |
Time, space, and reason |
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MALT instruction cum scoring sheet.
Sl | Method of administering the test | Instruction to fill up the next column | Step score | Final count |
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1 | Copy the figures |
Symmetrical figure…0 |
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2 | Group similar objects |
Number of objects misgrouped | …/2 |
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3 | Trace the sequence |
Score the time in seconds |
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Name the animals |
Score time in seconds |
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B: the subject is asked to separate animals of a certain kind from among the toys | <15 s…0, else 1 |
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Build the wall |
A well built wall…0 |
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Instruction box |
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6 | Complete the task |
Able to complete the task…0 |
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7 | Remember the arrangement |
Number of objects recalled correctly | (6-…)/2 |
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8 | Cut along the line |
Deviation (in small units) |
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Time (in seconds) |
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9 | Recall the steps of the game till this point, in no specific order | Number of steps recalled | 8-… |
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The examiner asks a question pertaining to the sequence of the steps (what comes after X, say) | Correct answer…0 |
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10 | Identify the sound of the bell |
Unable to identify…1 |
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11 |
Trace the path |
Time (in seconds) |
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Deviation (in small grids on the graph paper) |
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12 | What from the shop? |
Incorrect…1 |
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13 | How much to pay? |
Incorrect…1 |
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14 | Choose the shortest path |
Incorrect…1 |
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15 | Quiz |
Number of questions answered | 4-… |
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16 | Time, space, and reason | A wrong answer to the question pertaining to spatial and temporal orientation, and silence in response to the reasoning question would be marked as “D” (for disoriented) |
MALT test board. The test is administered clock-wise starting from Step 1, “Copy the figures.” The red steps test memory, green-cognition, and yellow-psychomotor skills. The scores are noted on instruction cum scoring sheet (Table
To score the performance on MALT, we took into account both accuracy and speed of performance. Based upon the performance of initial 10 controls in the test, we fixed an upper limit of 1 minute for each of steps 3, 5, and 6. The maximum scores on the entire test was 60 and 20 each on cognition, memory, and psychomotor skills. Higher scores implied greater impairment in mental function.
Informed consent was obtained from each patient included in the study and the study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the ethics committee of Stanley Medical College and Hospital. The study was conducted at the Department of Medical Gastroenterology, Stanley Hospital. Forty proven cirrhotic patients were recruited as cases from among the out-patients and in-patients registered in our department. The diagnosis was based on clinical presentation and ultrasound findings. Patients with neurological deficit, obvious overt encephalopathy, alcohol abuse 72 hours prior to the test, or those on sedatives or psycho-active drugs in the preceding 24 hours were excluded. Patients with cardiac failure, renal disease, and chronic obstructive airway disease were also excluded. It was ensured that the patients had not received lactulose, lactitol, or antibiotics like rifaximin, neomycin, or quinolones in the past three months. Controls were healthy individuals screened at the Master Health Checkup scheme in the hospital.
All controls and patients had critical flicker frequency test using portable battery-powered Hepatonorm Analyzer, Accelab GmbH, Kusterdingen, Germany. The test was done in a quiet dark room. The analyzer evoked an intrafoveal light stimulus with defined pulses [
The subjects (cases and controls) were then brought into a well lit room and were allowed a relaxation time of 15 minutes after which MALT was administered by two trained medical professionals (SD and SM). The patient and the tester are seated across a table with the test board, question cards, an audio device, and a table clock. The performance of the patient was noted on the instruction/scoring sheet, including time to completion.
Both MALT and CFF were done in the same sitting. Patients were randomly assigned to MALT or CFF as the first test. Both tests were executed by two different persons (SD and SM) who were blinded to the other examiner’s results. The performers administering the tests were trained by experienced clinicians so as to minimize the intra- and interobserver variations.
Chi-square test was used to assess differences between qualitative variables. Student’s
The test-retest reproducibility was assessed using the Bland-Altman plot. Twenty subjects including 10 cases and 10 controls were administered MALT twice at an interval of a six hours. It was ensured that patients being evaluated were not on lactulose, lactitol, neomycin, or any sedative meanwhile. The test was administered by the same examiner. The scores of the first and the second session of MALT were compared. The report was prepared in accordance with standards for reporting diagnostic accuracy, STARD guidelines (Figure
Study design flowchart according to the STARD guidelines.
The study comprised of 40 patients with cirrhosis (hereinafter referred to as “cases”) and included 25 males (62.5%). There were 36 healthy controls (hereinafter referred to as “controls”) and included 16 males (44.44%). The base line characteristics of controls and cases are shown in Table
Demographic characteristics of cases and controls.
Demographic characteristic |
Controls ( |
Cases ( |
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Age (years) | 42 ± |
46 ± |
Male : female | 16/20 | 25/15 |
Education |
13/23 | 13/27 |
Income per month (in US dollars) | 15.36 ± 14.51 | 10.77 ± 7.40 |
The etiology of cirrhosis was alcohol in 15 patients (37.5%), HCV in 13 (32.5%), nonalcoholic fatty liver disease in 6 (17.5%), autoimmune in 1 (2.5%), and cryptogenic in 8 (20%). There were 22 patients (55%) belonging to Child-Pugh class A and 18 (45%) to class B. Among the cirrhotics, there were 18 variceal bleeders (45%) and 2 patients (5%) had coagulopathy. 4 patients (10%) had refractory ascites, 2 patients (5%) had spontaneous bacterial peritonitis, and 8 others (20%) had urosepsis.
Using 38 Hz as CFF cut-off for MHE, 16 out of the 40 cirrhotics had MHE (40%), 8 each (50%) belonged to Child Class A and Child Class B. Among the 24 cirrhotics without MHE, 14 (58.33%) belonged to Child A and 10 (41.66%) to Child B at the time of MHE testing. The mean CFF for the cases was
Demographics within the cirrhosis group.
Cirrhotics without MHE |
Cirrhotics with MHE |
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Age | 43.5 ± |
50 ± |
Years of education | 6.4 ± |
3.06 ± |
Gender (M/F) | 16/8 | 9/7 |
Cirrhosis etiology (Alcohol/HCV/HCV+Alcohol/NASH/Others) | 09/05/00/04/06 | 03/05/03/02/03 |
MELD score (median) | 11 | 14 |
Child score (A/B) | 14/10 | 8/8 |
Total bilirubin (median) | 1.5 | 1.6 |
INR (median) |
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Serum creatinine (median, in mg/dL) |
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MALT scores | 14.8 ± |
24.8 ± |
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Intergroup comparison for CFF reading and MALT scores. The panel (a) compares the CFF readings between the controls, the non-MHE cirrhotics, and MHE (+) cirrhotics. The panel (b) compares the MALT scores between the same groups.
The cases performed worse than controls on MALT. The controls scored
(a) ROC curve using CFF as gold standard and MALT score 20 as cut-off for the diagnosis of MHE. (b) Bland-Altman plot for the test-retest agreement of MALT.
The test-retest variability was assessed using the intraclass correlation coefficient, ICC = 0.894 (
The Hepatonorm analyzer, manufactured in Germany, is an electronic device which runs on a battery that needs to be regularly changed. The price per unit is US$3053 and one day long user training costs US$230. The MALT board and its kit cost approximately US$5. The cost ratio is of the order of 105. The mean time of administration for both MALT and CFF was
The highlights of the study are (a) a significant correlation between CFF and MALT scores in the population under study (
A number of neuropsychological tools have been used to diagnose cognitive deficits in patients with cirrhosis. These include an extended neuropsychological assessment, shorter batteries, and computerized tests. The extended neuropsychological assessment is based upon the expert judgment and is difficult to validate [
The introduction of MALT has been based on the fundamental assumption that the currently available tests for the diagnosis of MHE are designed to test for one or two domains of mental impairment, and are expensive or not widely available [
The prevalence of MHE among the cirrhotics in the present study is 40%. It is in agreement with the prevalence of 41% reported in a recent study involving 200 cirrhotics from North India while on the higher side compared to 30% reported in the study from Spain using PHES [
MALT is a psychometric test which displays day-to-day activity on a colorful board and disagreement between administrators of the test is significantly less (85% agreement in interobserver studies). Though the tasks on the game board remain the same, the elements of the tasks are not printed on the board but on multiple cards. This is to avoid a memory effect that accompanies any psychometric test. MALT includes steps like “build the wall” and “trace the path” which are analogous to block design and trail tracing test. In MALT, the subject is not asked to connect numbers, but rather to trace the sequence of a day-to-day event from morning to night, which in true sense does not need a level of literacy.
Although the majority of surveyed hepatologists in Spain and the United States agreed that MHE was a significant problem requiring testing during out-patient visits, only a few were able to actually perform the test during their day-to-day clinical practice [
This study largely aimed to design a psychometric battery to diagnose MHE in our population, which is useful for the illiterate patients and to check its reliability. The high sensitivity and specificity of MALT, its ease of administration, reproducibility, and cost-effectiveness seen in this pilot beckon further validation studies involving larger sample sizes.
The authors declare that there is no conflict of interests regarding the publication of this paper.