Clinicopathologic correlates of hepatitis C virus in brain: A pilot study

Abstract

Hepatitis C virus (HCV) has been detected in the brain tissues of 10 individuals reported to date; it is unclear what clinical factors are associated with this, and with what frequency it occurs. Accordingly, a pilot analysis utilizing reverse transcriptase-polymerase chain reaction (RT-PCR) to detect and sequence HCV in premortem plasma and postmortem brain and liver from 20 human immunodeficiency virus (HIV)-infected and 10 HIV-naïve individuals was undertaken. RNA encoding the first 126 amino acids of the HCV E1 envelope protein and the majority of the E1 signal sequence was analyzed in parallel with an 80-base-long segment of the 5′ untranslated region (UTR). Liver HCV was detected only in subjects with premortem HCV viremia (10 HIV-infected and 3 HIVnaïve). Brain HCV was detected in 6/10 HCV/HIV-coinfected and 1/3 HCV-monoinfected subjects. In the setting of HIV, the magnitude of plasma HCV load did not correlate with the presence of brain HCV. However, coinfected patients with brain HCV were more often off antiretroviral therapy and tended to have higher plasma HIV loads than those with HCV restricted to liver. Furthermore, premortem cerebrospinal fluid (CSF) analysis revealed that HCV/HIV-coinfected patients with brain HCV had detectable CSF HIV, whereas those without brain HCV had undetectable CSF HIV loads (P = .0205). Neuropsychologic tests showed a trend for hierarchical impairment of abstraction/ executive functioning in HIV/HCV coinfection, with mean T scores for HIV monoinfected patients 43.2 (7.3), for liver-only HCV 39.5 (9.0), and for those with HCV in brain and liver 33.2 (5.1) (P = . 0927). Predominant brain HCV sequences did not match those of the plasma or liver in 4 of the 6 coinfected patients analyzed. We conclude that in the setting of HIV/HCV coinfection, brain HCV is a common phenomenon unrelated to the magnitude of HCV viremia, but related to active HIV disease and detectable CSF HIV. Furthermore, there is sequence evidence of brain compartmentalization. Differences in abstraction/executive function of HCV/HIV coinfected patients compared to HIV monoinfected warrant further studies to determine if neuropsychiatric effects are predicated upon brain infection.

Hepatitis C Virus Neuroinvasion: Identification of Infected Cells

“…Negative-strand HCV RNA was found in autopsy brain tissue (34), and two independent groups of researchers reported that the brain-derived HCV variants were more closely related to the virus present in the lymphoid system than to the virus circulating in serum (10,34). Differences between HCV sequences in the brain and those circulating in plasma also were reported by others (8,28). Finally, a recent study by Letendre et al (23) demonstrated the presence of HCV proteins in brain tissue by Western blotting and immunostaining.…”

Neuropsychological alterations in hepatitis C infection: The role of inflammation

“…However, data on the association between the virus in the brain and impaired cognitive function are still lacking. Indeed, replication of quasispecies is very low within the brain; HCV RNA is almost undetectable in the cerebrospinal fluid [33,34] and there is no correlation between viral load and cognitive impairment in patients with HCV infection [20] . However, this is sometimes also the case for other HCV-related complications, such as cryoglobulinemia or vasculitis [35] .…”

Neues bei HIV und Neuro-Aids

“…10 000 (15 % aller HIV-Patienten), in den USA 240 000 (30 % aller HIV-Infizierten) mit HCV koinfiziert [73]. Die wenigsten dieser Patienten sind adäquat therapiert und es wird angenommen, dass eine HCV-Koinfektion mit einem beschleunigten Verlauf der HIV-Infektion bei unbehandelten Patienten assoziiert sein könnte [74]. Neurologische Symptome finden bei HCV-Patienten mehr und mehr Beachtung.…”