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17-40% of HCV-Infected Report Impaired Psych Function in HIV+
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"Neuropsychological test performance in patients co-infected with hepatitis C virus and HIV"
AIDS: Volume 19 Suppl 3 October 2005
....17-41% of HCV & coinfected patients had impaired performance on neurolopsychological testing...
Perry, Williama; Carlson, Meghan Da; Barakat, Fatmaa; Hilsabeck, Robin Ca,b; Schiehser, Dawn Ma; Mathews, Christophera; Hassanein, Tarek Ia
From the aHepatology Neurobehavioral Research Program, University of California, San Diego, CA, USA
bDepartment of Neuropsychiatry and Behavioral Sciences, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
..... The findings from this study show that a significant number of patients with chronic HCV, either alone or when co-infected with HIV, have deficits in the domains of attention, concentration and psychomotor speed when tested using standard neuropsychological tests......
...All of the neuropsychology measures were correlated moderately with fibrosis stage such that advanced liver disease (greater fibrosis) was associated with a poorer neuropsychological test performance...
..... The current findings of a relationship between neuropsychological performance and fibrosis severity add further support to earlier studies that found that HCV patients have deficits on a number of neuropsychological tests that reflect frontostriatal functioning (i.e. tests of attention, psychomotor and working memory) but demonstrated intact verbal skills and visuoconstructional abilities. In addition, it has been shown that neuropsychological impairment is correlated with a decrease in the bilateral frontotemporal and right basal ganglia regions in end-stage cirrhotic patients compared with control subjects....
.... The present findings did not support our primary hypothesis that there would be significant differences on measures of attention, concentration and psychomotor speed between patients with HCV alone and HCV/HIV-co-infected patients. This might be related to the fact that 65% of the HCV/HIV-co-infected group had undetectable HIV levels as well as controlled disease.... The absence of our expected findings could also be explained by the limitations in our study....
Abstract
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.
Results
There were no differences in age or years of education between the HCV-alone, and HCV/HIV-co-infected groups (t[76] = 1.69, P = 0.096), (t[76] = 1.34, P = 0.19).
There were also no differences on the TMT part A (F[4,75] = 1.05, P = 0.39), TMT part B (F[4,75] = 1.86, P = 0.12), WAIS-III symbol search (F[4,26] = 1.51, P = 0.23), and the SDMT (F[4,74] = 0.88, P = 0.48) based upon race.
There were no differences on neuropsychological test performance between the HCV-alone and HCV/HIV-co-infected group for any of the neuropsychological measures (TMT A: z = -1.31, P = 0.19; TMT B: z = -0.66, P = 0.51; SDMT: z = -0.07, P = 0.95; WAIS-III symbol search: z = -0.05, P = 0.96).
The percentage of impaired performance on the neuropsychological measures was compared against the percentage expected in the normal population as reported by Heaton et al. [24]. Using ƒÔ2 analyses the HCV-alone group had more impairment than expected on the TMT part B (ƒÔ2 = 0.646, P < 0.025), the SDMT (ƒÔ2 = 12.62, P < 0.001), and symbol search (ƒÔ2 = 4.33, P < 0.05).
The degree of impairment did not reach statistical significance for the TMT part A (ƒÔ2 = 3.78, P < 0.10). The HCV/HIV-co-infected group reached statistical significance for the percentage of impairment on the SDMT (ƒÔ2 = 23.45, P < 0.001).
The percentage of impairment on the remaining three tests was not significantly different from the percentage found in the normative sample (TMT part A: ƒÔ2 = 1.32; TMT part B: ƒÔ2 = 0.62; symbol search: ƒÔ2 = 0.96). To characterize the degree of neuropsychological impairment further for both groups we calculated that 27% of the HCV-alone group and 13.8% of the HCV/HIV-co-infected group was impaired on two or more of the neuropsychological tests. The percentage of impairment between the HCV-alone and the HCV/HIV-co-infected groups was not statistically significant for any of the neuropsychological measures (TMT part A: ƒÔ2 = 0.63; TMT part B: ƒÔ2 = 0.30; the SDMT: ƒÔ2 = 0.40; symbol search: ƒÔ2 = 0.68). However, the HCV-alone group had a significantly greater percentage of impairment on two or more neuropsychological tests than did the HCV/HIV-co-infected group (ƒÔ2 = 3.90, P < 0.05).
There was no relationship between neuropsychological performance and the ALT and CD4 cell counts. The relationship between fibrosis stage and performance on the neuropsychological measures was also evaluated. As there were few cases of cirrhosis in the HCV/HIV-co-infected group, both groups were combined for the analysis. All of the neuropsychology measures were correlated moderately with fibrosis stage such that advanced liver disease (greater fibrosis) was associated with a poorer neuropsychological test performance.
Table 2. Median raw scores (range) and percentage of impairment (i.e. > 1 SD below the mean) on the four neuropsychological tests in HCV-alone and HCV/HIV-co-infected patients.
Discussion
The findings from this study show that a significant number of patients with chronic HCV, either alone or when co-infected with HIV, have deficits in the domains of attention, concentration and psychomotor speed when tested using standard neuropsychological tests. The extent of the deficit is different depending upon the measure used. Both the HCV-alone and the HCV/HIV-co-infected group demonstrated impairment on the SDMT. We have previously reported that the SDMT yielded the largest percentage of impairment among our measures of attention, concentration and psychomotor speed [9], suggesting that this measure may be sensitive in detecting neuropsychological functioning among patients with HCV infection.
The HCV-alone group performed in the impaired range on three of the four administered tests, whereas the HCV/HIV-co-infected group performed in the impaired range on one of the four measures. More than a quarter of the HCV-alone group was also impaired on two or more of the tests administered compared with 13.8% of the HCV/HIV-co-infected group. Similar to our findings, Heaton and colleagues [26] reported that 30% of asymptomatic HIV-seropositive patients had impaired neuropsychological test performance on two or more measures, whereas Starace and colleagues [27] found 22% impaired neuropsychological performance among HIV-seropositive individuals. These impairment rates are higher than the 2.5% reported for healthy controls [27]. The finding that the HCV-alone group had a higher percentage of impaired performance, albeit not significantly different, than did the HCV/HIV-co-infected group on our tests may be related to the greater number of cirrhotic patients in the HCV-alone group. Consistent with this supposition is our finding that the severity of liver disease was positively related to a poorer test performance. These findings are also consistent with previous results that HCV is associated with deficits in attention, concentration and psychomotor speed [8,9].
Similar to other studies, neuropsychological performance did not correlate with ALT and CD4 cell counts [19]. As a result of the small numbers of patients with detectable HIV viral load, a correlation between neuropsychological test performance and viral load was not performed. However, there was a correlation between neuropsychological impairment and an increase in the severity of liver fibrosis. Moss and colleagues [28] reported that neuropsychological deficits in patients with chronic liver disease correlated with the degree of hepatic dysfunction, although the biochemical measures of hepatic injury (ALT levels) did not demonstrate a significant relationship with any neuropsychological measure. The absence of a correlation with biochemical measures of hepatic injury (ALT) is explained by the fact that these measures do not reflect the stage or extent of the liver damage in a disease characterized by slow progressive changes; however, they reflect an ongoing level of hepatic injury.
The current findings of a relationship between neuropsychological performance and fibrosis severity add further support to earlier studies that found that HCV patients have deficits on a number of neuropsychological tests that reflect frontostriatal functioning (i.e. tests of attention, psychomotor and working memory) but demonstrated intact verbal skills and visuoconstructional abilities [8]. In addition, it has been shown that neuropsychological impairment is correlated with a decrease in the bilateral frontotemporal and right basal ganglia regions in end-stage cirrhotic patients compared with control subjects [29].
The present findings did not support our primary hypothesis that there would be significant differences on measures of attention, concentration and psychomotor speed between patients with HCV alone and HCV/HIV-co-infected patients. This might be related to the fact that 65% of the HCV/HIV-co-infected group had undetectable HIV levels as well as controlled disease. The relative similarity in the neuropsychological deficits among HCV-alone and HCV/HIV-co-infected patients suggests that there may be an overlap in the underlying abnormal frontostriatal circuitry, which is known to be associated with abnormal attention and psychomotor speed. It has also been shown that patients co-infected with both HCV and HIV develop hepatic changes more rapidly than patients with HCV alone [30]. This interaction might result in an increased burden on the CNS and additive effects on neuropsychological performance, particularly perpetuating deficits in attention and working memory. However, von Giesen and colleagues [31] recently reported that HCV co-infection did not exacerbate psychomotor slowing in their sample of HIV-positive patients. Collectively, these findings underscore the importance of disease stage rather than the presence or absence of the virus itself.
The absence of our expected findings could also be explained by the limitations in our study. We tested a relatively small group of patients, and therefore we may be underpowered with respect to finding subtle neuropsychological differences between the two relatively healthy clinical samples. It is also possible that our measures of attention and concentration may not be sensitive enough to uncover group differences. In addition, we restricted our neuropsychological measures to tests of attention, concentration and psychomotor speed. The present findings, therefore, cannot be generalized to other cognitive domains, such as learning and memory or visuoconstructional abilities, which may be different between the two groups. Finally, inspection of the HCV/HIV-co-infected sample revealed that our co-infected group consisted of a relatively healthy sample (mean CD4 cell count of 479 and only seven patients with severe fibrosis or cirrhosis). Given that previous work has suggested that neuropsychological deficits are related to the stage of liver fibrosis, it is possible that the lack of a difference in neuropsychological performance can be attributed to the relative lack of advanced liver fibrosis among the HCV/HIV-co-infected patients. In this regard we can speculate that the successful treatment of HIV and the absence of cirrhosis may spare patients co-infected with HCV/HIV from significant neuropsychological impairment. This finding is consistent with the work of Arendt and colleagues [32], who have repeatedly shown that HIV-associated psychomotor slowing improves with treatment. Clearly, larger studies in heterogeneous groups of HCV and HCV/HIV-co-infected patients using a more extensive neuropsychological test battery are needed to determine conclusively whether there are differences in neuropsychological functioning between HCV and HCV/HIV-co-infected patients.
Sponsorship: This work was partly supported by National Institutes of Health grant no. 5 P30 AI36214-05 to University of California, San Diego Center for AIDS Research.
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