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Detection of hepatitis C virus sequences in brain tissue obtained in recurrent hepatitis C after liver transplantation
Author(s) -
Vargas Hugo E.,
Laskus Tomasz,
Radkowski Marek,
Wilkinson Jeff,
Balan Vijay,
Douglas David D.,
Harrison M. Edwyn,
Mulligan David C.,
Olden Kevin,
Adair Debra,
Rakela Jorge
Publication year - 2002
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1053/jlts.2002.36393
Subject(s) - hepatitis c virus , medicine , hepatitis c , virology , liver transplantation , transplantation , viral replication , hepatitis , reverse transcriptase , virus , flaviviridae , hepacivirus , pathology , rna , biology , gene , genetics
Abstract Patients with chronic hepatitis C frequently report tiredness, easy fatigability, and depression. The aim of this study is to determine whether hepatitis C virus (HCV) replication could be found in brain tissue in patients with hepatitis C and depression. We report two patients with recurrent hepatitis C after liver transplantation who also developed severe depression. One patient died of multiorgan failure and the other, septicemia caused by Staphylococcus aureussis. Both patients had evidence of severe hepatitis C recurrence with features of cholestatic fibrosing hepatitis. We were able to study samples of their central nervous system obtained at autopsy for evidence of HCV replication. The presence of HCV RNA–negative strand, which is the viral replicative form, was determined by strand‐specific Tth‐based reverse‐transcriptase polymerase chain reaction. Viral sequences were compared by means of single‐strand conformation polymorphism and direct sequencing. HCV RNA–negative strands were found in subcortical white matter from one patient and cerebral cortex from the other patient. HCV RNA–negative strands amplified from brain tissue differed by several nucleotide substitutions from serum consensus sequences in the 5′ untranslated region. These findings support the concept of HCV neuroinvasion, and we speculate that it may provide a biological substrate to neuropsychiatric disorders observed in patients with chronic hepatitis C. The exact lineage of cells permissive for HCV replication and the possible interaction between viral replication and cerebral function that may lead to depression remain to be elucidated.