icon-folder.gif   Conference Reports for NATAP  
  AASLD (American Association for the Study of Liver Diseases)
Nov 2-5, 2002, Boston, MA
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Hepatitis C Found In Cerebrospinal Fluid
Reported By Jules Levin
  Researchers from several clinics (abstract 530, Laskus et al, Mayo Clinic, Scottedale, AZ) reported at AASLD findings from their research that HCV can be found in the cerebrospinal fluid (CSF) suggesting HCV can enter the brain; and peripheral blood mononuclear cells (PBMC) may be carrying HCV into the CSF. An ongoing controversy is whether chronically HCV infected patients experience neurological-related symptoms due to HCV including fatigue, cognitive impairment, loss of memory or thinking skills, emotional distress, and depression. For years patients have complained of these symptoms and for years many doctors have been very skeptical. On the NATAP website there are seven research articles and papers finding that HCV can be found in the CSF, may enter the brain, and may cause cognitive impairment. Below is the latest study finding similarly. In addition, Resti (Clinical Infectious Diseases, 2002;35:236-239) reported that HCV infection was found, by nested reverse-transcription polymerase chain reaction analysis, in the PBMCs of 33 IVDUs and of 13 non-IDUs (P = .00003). Injection drug use is thought to impair function of the immune system and induce tolerance to viruses and therefore HCV infection of PBMCs could be more likely to occur in injection drug users (IDUs) with HCV infection; link to article:www.natap.org/2002/september/090902_1.htm
HCV infection has been implicated in diseases of the central nervous system (CNS) and HCV-RNA negative-strand sequences, which are viral replicative intermediaries, have been recently found in autopsy brain tissue samples from HCV-infected patients (Radkowski et al, J Virol 2002, 76:600-608). It was speculated that HCV replication in CNS occurs in cells of macrophage/monocyte lineage similarly to the mechanism postulated for HIV-1 neuroinvasion. However, it is unclear how HCV enters the CNS. All basic groups of leukocytes: T-cells, B-cells, macrophage/monocytes and NK-cells have the ability to enter the brain under certain conditions and certain monocyte family members are constantly being replaced as part of normal physiology. These cells could carry the HCV across the blood-brain. The aim of this study is to determine whether peripheral blood mononuclear cells (PBMC) could carry HCV into CNS. Researchers studied HCV-RNA in cerebrospinal fluid (CSF), CSF cells, serum and PBMC from 13 patients infected with HCV; 10 of these patients were HIV-1-positive. Amplified HCV sequences were compared by direct sequencing, sequencing after cloning, and by single-strand conformational polymorphism (SSCP). The presence of viral replication was determined by strand-specific detection of HCV-RNA negative strands. This assay was capable of detecting approximately 100 genomic equivalent (eq) molecules of the correct strand while unspecifically detecting 108 genomic eq of the incorrect strand (Laskus et al, J Virol 1998, 72, 3072-3075). Lumbar puncture was performed for diagnostic purposes; three patients had neurotoxoplasmosis, 2 patients had tuberculosis with suspected CNS involvement; 1, neurosyphilis; 1, reactive meningitis; 1, multifocal leukoencephalopathy; the remaining 5 were diagnosed to have aseptic meningitis. Results: All 13 patients were HCV RNA positive in serum and 12 were HCV RNA positive in PBMC. HCV-RNA was also detected in 8 out of 13 CSF cellular pellets but only in 2 CSF supernatants. HCV-RNA negative strand was detected in CSF cell pellets from 2 patients and in PBMC from another 2 patients. The titer of the negative strand was approximately one log lower than the titer of the positive strand. In 4 patients the dominant viral variant amplified from CSF was different than the one circulating in serum. However, in each of these 4 cases the CSF strain was closely related to the one found in PBMC. In 2 of these patients sequences recovered from CSF cells were classified as belonging to a different genotype than those found in serum but were of the same genotype as those found in PBMC. The above findings were confirmed by analyzing two different viral regions. In addition, CSF-derived viral sequences contained a number of variants, which were present neither in PBMC nor serum-derived virus suggesting an independent viral evolution in the cells present in CSF and arguing for the presence of an independent viral compartment in the CNS. In conclusion researchers reported they found a common presence of HCV RNA in CSF of HCV infected patients. HCV was associated with cellular compartment of CSF. In patients harboring different HCV strains in serum and PBMC, CSF-derived strains were more closely related to PBMC than to serum derived HCV. These findings suggest that PBMC could carry the virus into CNS and provide a mechanism for HCV "neuroinvasion". Subsequent CNS infection is possible but its clinical consequences remain to be defined.