Meghan D. Carlson

Cognitive functioning and psychiatric symptomatology in patients with chronic hepatitis C

Hepatitis C virus (HCV) infection is a major public-health-care problem, with over 170 million infected worldwide. Patients with chronic HCV infection often complain of various cognitive problems as well as symptoms of depression, anxiety, and fatigue. Relatively little is known, however, about the specific cognitive deficits that are common among HCV patients, and the influence of psychiatric symptomatology on cognitive functioning. In the current study of 21 chronically infected HCV patients, we assessed subjective cognitive dysfunction, depression, anxiety, and fatigue and compared these symptom areas to cognitive tests assessing visuoconstruction, learning, memory, visual attention, psychomotor speed, and mental flexibility. Results revealed that cognitive impairment ranged from 9% of patients on a visuoconstruction task to 38% of patients on a measure of complex attention, visual scanning and tracking, and psychomotor speed, and greater HCV disease severity as indicated by liver fibrosis was associated with greater cognitive dysfunction. Objective cognitive impairment was not related to subjective cognitive complaints or psychiatric symptomatology. These findings suggest that a significant portion of patients with chronic HCV experience cognitive difficulties that may interfere with activities of daily living and quality of life. Future research using cognitive measures with HCV-infected patients may assist researchers in identifying if there is a direct effect of HCV infection on the brain and which patients may be more likely to progress to cirrhosis and hepatic encephalopathy.

Neuropsychological test performance in patients co-infected with hepatitis C virus and HIV.

Objective:To determine the effect of co-infection on neuropsychological performance in relatively healthy hepatitis C virus (HCV)-alone patients when compared with HCV/HIV-co-infected patients. Design:To test whether the burden of co-infection with HCV and HIV on the central nervous system results in increased cognitive deficits, we tested 47 HCV-alone and 29 HCV/HIV-co-infected patients on a neuropsychological screening battery of tests of attention, concentration and psychomotor speed. Methods:The neuropsychological test performance of HCV-alone and HCV/HIV-co-infected patients was compared with normative samples. The test performance between HCV-alone and HCV/HIV-co-infected patients was also assessed. Patients with chronic liver disease were divided on the basis of disease severity as determined by fibrosis stage, according to the METAVIR system. Neuropsychological test performance was correlated with fibrosis stage. Results:As previously reported, HCV patients independent of co-infection status demonstrated deficits on neuropsychological measures of attention, concentration and psychomotor speed. No significant differences were found between patients with HCV-alone and HCV/HIV-co-infected patients on the neuropsychological measures. There was a relationship between neuropsychological test performance and fibrosis stage. Conclusion:Relatively healthy patients with HCV (either alone or when co-infected with HIV) may have deficits in the domains of attention, concentration and psychomotor speed. In this study no significant differences were found between patients with HCV alone and HCV/HIV-co-infected patients on neuropsychological measures, but as previously demonstrated, greater fibrosis was associated with poorer performance.

Effect of interferon-α on cognitive functioning in patients with chronic hepatitis C

Treatment with interferon-alpha (IFN-alpha) has been shown to adversely affect cognitive functioning in patients with a variety of medical disorders, but information about the effects of IFN-alpha on cognitive functioning in patients with chronic hepatitis C (CHC) is limited. The purpose of this study was to examine the effects of IFN-alpha on neuropsychological test performance in CHC patients. Participants were 30 patients with CHC, 11 who underwent IFN-alpha therapy and 19 who did not. All participants were tested at baseline (i.e., pretreatment) and approximately 6 months later with the Symbol Digit Modalities Test and Trail Making Test. Results revealed that the treatment group performed significantly worse than untreated CHC patients on Part B of the Trail Making Test after approximately 6 months of treatment. No significant group differences were found on Part A of the Trail Making Test or Symbol Digit Modalities Test. Findings suggest that CHC patients undergoing treatment with IFN-alpha may experience reduced abilities to benefit from practice but suffer no decrements in performance after 6 months of treatment. Additional research is needed to replicate these findings and to explore risk factors for susceptibility to IFN-alpha-induced effects.

Role of Sleep Disturbance in Chronic Hepatitis C Infection

Chronic infection with the hepatitis C virus (CHC) is associated with physical and mental symptoms including fatigue and depression that adversely affect quality of life. A related complaint, sleep disturbance, has received little attention in the literature, with the exception of sleep changes noted in cirrhosis and end-stage liver disease. We present an overview of studies indicating sleep problems in patients with CHC, with about 60% to 65% of individuals reporting such complaints. Evidence suggests that impairments in sleep quality exist independent of antiviral therapy with interferon-α and prior to advanced stages of liver disease. Further investigation of sleep disturbance in CHC patients with a mild stage of liver disease may provide important information on disease course as well as allow additional opportunities for patient support.

The category test perseveration, loss of set, and memory scales: three new scales and their relationship to executive functioning measures.

The Category Test (CT) is a neuropsychological measure that taps into multiple domains of complex reasoning but yields a single error score, limiting the use of the test. In this study, three new CT scales were developed to assess specific aspects of executive dysfunction: Perseveration, Failure to Maintain Cognitive Set, and Inability to Recall and Re-Initiate Past Behavior. The relationship of these scales to well-established neuropsychological measures was examined in head-injured individuals and schizophrenia patients. The CT Perseveration score was correlated with the Wisconsin Card Sorting Test (WCST) Perseverative Responses score, but also with measures from the Wechsler Memory Scale-Revised and the California Verbal Learning Test. The CT Memory score correlated with other memory measures, but also with the WCST Perseveration measure. Although future studies designed to test discriminant and convergent validity are warranted, these scales may be useful in determining specific aspects of impaired CT performance.

Effects of the combination of PEG-interferon alpha-2B and ribavirin on the inflammation and fibrosis scores of patients with chronic hepatitis C infection who were virologic non-responders to interferon alpha-2B and ribavirin

Effects of the combination of PEG-interferon alpha-2B and ribavirin on the inflammation and fibrosis scores of patients with chronic hepatitis C infection who were virologic non-responders to interferon alpha-2B and ribavirin