Neurocognitive Impairment Persists after Episodes of Hepatic
Encephalopathy in People with Liver Cirrhosis
Changes in working memory, psychomotor speed, and
other neurocognitive measures persist in patients
with hepatic encephalopathy due to decompensated liver
cirrhosis, according to research presented at the
45th Annual Meeting of the European Association for
the Study of the Liver (EASL
2010) last month in Vienna. A related study presented
at the Digestive Disease Week conference (DDW 2010)
last week in New Orleans found that more than half
of people with compensated cirrhosis (mostly due to
hepatitis C) showed signs of neurocognitive impairment,
indicating that mild hepatic encephalopathy is common
even among individuals without severe liver disease.
encephalopathy is a form of brain disease caused by the build-up
of toxins such as ammonia in people whose livers are so damaged
they cannot perform their normal filtering function (a condition
known as decompensated
cirrhosis). Over years or decades, chronic
hepatitis B and C can
progress to decompensated liver disease and ultimately end-stage
Bajaj and colleagues from Virginia Commonwealth University designed
a cross-sectional study to evaluate whether recurrent episodes
of hepatic encephalopathy lead to persistent or progressive
encephalopathy is associated with physiological changes and
evidence of injury to neurons (the primary nervous system cells
that carry electrical signals) and astrocytes (a type of support
cell in the brain). Obvious mental status changes due to hepatic
encephalopathy can usually be reversed with treatment, but some
level of chronic cognitive impairment may persist, the investigators
noted as background.
This analysis included 64 patients with cirrhosis who had experienced
at least 1 prior episode of hepatic encephalopathy but were
currently in remission due to treatment with lactulose and/or
A majority of participants (about 60%) were men, the average
was 56 years, and the most common cause of cirrhosis was hepatitis
C (78%). With regard to therapy, 53 patients were treated with
lactulose only, 5 received rifaximin only, and 6 received both.
Participants underwent a battery of standard neurocognitive
measurements including the number connection test, digit symbol
test, block design test, and 2 inhibitory control tests. The
number of hepatic encephalopathy episodes and hospitalizations,
and the duration between the first hospitalization and current
testing, were then correlated with psychometric tests scores.
an average follow-up period of 13 months, participants experienced
a median of 2 episodes of hepatic encephalopathy (range
half the patients were hospitalized at least once due to
hepatic encephalopathy, with a median of 1 hospitalization
test scores were "highly abnormal" in all patients.
scores on all 4 tests were strongly correlated with a greater
number of hepatic encephalopathy episodes.
test performance and number of hospitalizations were also
significantly correlated, as was the time from the first
hepatic encephalopathy episode to testing.
on these findings, the researchers concluded that among patients
with liver cirrhosis, "deficits in working memory, psychomotor
speed, attention and response inhibition increase with number
and severity of episodes of overt hepatic encephalopathy."
In the study presented at DDW, Christopher Randolph and a team
of colleagues including Bajaj used a series of tests known as
the Repeatable Battery for the Assessment of Neuropsychological
Status (RBANS) to assess hepatic encephalopathy among more than
300 people with compensated cirrhosis.
Though typically not debilitating, mild hepatic encephalopathy
is associated with reduced quality of life and increased risk
of negative outcomes such as job loss and motor vehicle accidents,
the researchers noted. The International Society for Hepatic
Encephalopathy and Nitrogen Metabolism (ISHEN) recommends the
RBANS as the tool of choice for detecting mild encephalopathy
because it has well-established population norms and correlates
with impaired daily functioning and job loss.
This analysis included 301 participants screened for the ASTUTE
trial, a Phase 2b study to evaluate whether AST-120 (spherical
adsorbent carbon) is an effective therapy for mild hepatic encephalopathy.
Again, a majority were men, the average age was 55 years, and
hepatitis C was the most common cause of liver disease. About
80% were high school graduates and just over half attended college
(factors known to affect neurocognitive test scores).
group of patients was considerably healthier than those in the
previous study, however. They had MELD scores < 25,
had not received surgical shunts to re-route blood flow due
to portal hypertension, had not had an episode of overt hepatic
encephalopathy during the prior 3 months, and had not taken
lactulose, rifaximin, or neomycin during the past week.
Study participants had an average RBANS score of 74, compared
with 100 for the general population. Of the screened patients,
54% had a score below the tenth percentile after adjusting for
age and education, thus meeting the eligibility criteria for
randomization in the ASTUTE trial. The RBANS score could not
be predicted on the basis of age, sex, education level, or measures
of liver disease severity including platelet count, bilirubin
level, MELD score, or history of esophageal varices.
"The RBANS is a very useful tool for assessing neurocognitive
impairment in cirrhotic patients," the researchers concluded.
Using the RBANS, we found a neurocognitive impairment rate of
[54%] in a population of healthy appearing, well-compensated
cirrhotics, suggesting that mild hepatic encephalopathy is highly
prevalent in these patients. Mild hepatic encephalopathy was
not predicted by age, education, MELD score, or indicators of
EASL study: Departments of Gastroenterology, Hepatology,
Nutrition, and Biostatistics, Virginia Commonwealth University,
Richmond, VA; McGuire VA Medical Center, Richmond, VA.
DDW Study: Neurology, Loyola University Medical Center, Chicago,
IL; McGuire VA Medical Center, Richmond, VA; University of California
San Francisco Fresno Medical Education Program, Fresno, CA;
Permian Research Foundation, Odessa, TX; University of Florida,
Gainesville, FL; Tulane University, New Orleans, LA; Veterans
Medical Center San Deigo, San Diego, CA; Case Western Reserve
University, Cleveland, OH; Ocera Therapeutics, San Diego, CA.
J Bajaj, C Schubert, AJ Sanyal, and others. Severity of chronic
cognitive impairment in cirrhosis increases with number of episodes
of overt hepatic encephalopathy. 45th Annual Meeting of the
European Association for the Study of the Liver (EASL 2010).
Vienna, Austria. April 14-18, 2010. (Abstract).
C Randolph, J Bajaj, M Sheikh, and others. Mild Hepatic Encephalopathy
(HE) Assessed by the Repeatable Battery for the Assessment of
Neuropsychological Status (Rbans) Is Highly Prevalent in Ambulatory
Patients With Cirrhosis and Is Unrelated to Severity of Cirrhosis.
Digestive Disease Week (DDW 2010). New Orleans, May 1-5, 2010.