Hepatitis C virus replicates in the liver of patients who have a sustained response to antiviral treatment.
BACKGROUND
Positive-strand hepatitis C virus (HCV) RNA has been detected in the livers of patients who have achieved a sustained biochemical and virological response to antiviral therapy (hereafter, referred to as sustained responders), but negative-strand HCV RNA was undetectable in the hepatic tissue of these patients. We studied the presence of both positive- and negative-strand HCV RNA in the livers of 20 sustained responders with chronic hepatitis C whose response persisted for a mean (+/- standard deviation [SD]) of 47.4+/-32.8 months after treatment.


METHODS
HCV RNA was tested by strand-specific, real-time reverse-transcriptase polymerase chain reaction and by in situ hybridization in posttreatment liver biopsy samples (obtained a mean [+/- SD] 35.4+/-35.0 months after therapy) and in patients' peripheral blood mononuclear cells.


RESULTS
Positive-strand HCV RNA was found in 19 (95%) of 20 liver biopsy specimens, and negative-strand HCV RNA was found in 15 (79%) of the 19 samples that had positive-strand HCV RNA. These results were confirmed by in situ hybridization. Regarding peripheral blood mononuclear cells, 13 (65%) of 20 samples had positive-strand HCV RNA, and negative-strand HCV RNA was detected in 12 (92%) of the 13 samples with positive-strand HCV RNA. Liver necroinflammation was still present in the posttreatment liver biopsy specimens of 15 patients, and fibrosis was present in 7, although liver damage improved in all but 2 patients.


CONCLUSIONS
HCV persisted and replicated in the livers and peripheral blood mononuclear cells of most sustained responders. Thus, these patients did not experience HCV infection clearance, despite apparent clinical disease resolution.
Castillo
Inmaculada
I
Foundation for the Study of Viral Hepatitis, Madrid, 28015, Spain.
Rodríguez-Iñigo
Elena
E
López-Alcorocho
Juan Manuel
JM
Pardo
Margarita
M
Bartolomé
Javier
J
Carreño
Vicente
V
D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology; D005260:Female; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006526:Hepatitis C; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000821:virology*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis* / Q000097:blood; D019562:Viral Load; D014779:Virus Replication / Q000502:physiology*
D000998:Antiviral Agents; D012367:RNA, Viral