Discussion

This study examined neuropsychological dysfunction in patients with
chronic HCV. Results of this study revealed that a significant percentage of
patients with chronic HCV experience cognitive deficits, especially in the
domains of attention, learning, psychomotor speed, and mental flexibility. In
contrast, visuoconstructional skills and the ability to remember previously
learned information following a delay were relatively intact. This pattern of
cognitive dysfunction is similar to that reported in patients with mild
neurocognitive disorder associated with other chronic illness, such as HIV and
AIDS-related dementia, and is most consistent with a subcortical pattern of
deficits. The neuropsychological manifestation of subcortical deficits usually
includes slowed information processing speed, reduced word fluency, psychomotor
slowing, and impaired learning in the presence of good recall of previously
learned information and intact recognition memory. Verbal skills, such as
vocabulary and naming, and basic visuospatial and visuoconstructional abilities
are relatively unaffected.

Findings suggest that chronic HCV in combination with comorbid chronic
illness may result in increased levels of cognitive dysfunction, especially in
the presence of alcoholic hepatitis. This result cannot be attributed to age,
education, estimated IQ, overall QOL, fatigue, psychiatric medication usage,
substance use, or treatment with interferon.

Replication of this finding using larger, more homogenous samples
stratified by level of fibrosis is needed before definitively concluding that
there are no HCV-specific pathophysiological effects on cognitive functioning.

This study also reports neuropsychological impairment in patients who have
not yet developed cirrhosis. Impaired performances were found in up to 50% of
noncirrhotic patients, depending on the neuropsychological function tested. Of
the cognitive functions measured, only visuoconstructional ability was within
normal limits for all noncirrhotic patients. Maintaining attention and
concentration for more than a couple of minutes while performing accurately
(i.e., Digit Cancellation) was the most difficult task for noncirrhotic
patients, with 50% taking an abnormally long time to complete the task and 28.9%
making a significant number of omission errors. In addition, about 20% of
noncirrhotic patients performed in the impaired range on 3 other measures
involving attention/concentration, visual scanning and tracking, psychomotor
speed, and mental flexibility (i.e., Parts A and B of the TMT and SDMT). These
results suggest that attention and concentration may be the cognitive skill most
affected early in the course of chronic liver disease.

In summary, there were no significant differences in neuropsychological
test scores between HCV-infected patients and patients with other chronic liver
diseases. However, a greater proportion of patients with HCV plus a comorbid
illness performed in the impaired range than patients with HCV only or another
type of chronic liver disease. Greater fibrosis was significantly associated
with poorer cognitive functioning. Although patients with cirrhosis generally
performed more poorly on neuropsychological measures than precirrhotic patients,
a significant percentage of patients without cirrhosis were found to exhibit
cognitive deficits. In conclusion, results of this study suggest that HCV and
other chronic liver diseases adversely affect cognitive functioning, even in the
absence of cirrhosis. Attention and concentration abilities appear to be
affected earliest in the disease process, although problems with learning,
psychomotor speed, and mental flexibility are also present to a lesser extent.
These deficits, regardless of their cause, may affect QOL and performance in the
work and home environments. Hence, early identification and treatment of chronic
liver disease could be critical in diminishing detrimental effects on brain
function. The degree of cognitive dysfunction of patients with chronic liver
disease should be considered when evaluating the functional capacity of these
patients.



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