title: Persistence of hepatitis C virus in patients successfully treated for chronic hepatitis C.
abstract: It is unclear whether the current antiviral treatment for chronic hepatitis C virus (HCV) infection results in complete elimination of the virus, or whether small quantities of virus persist. Our study group comprised 17 patients with chronic HCV who had sustained virological response (SVR) after interferon/ribavirin treatment. Serum and peripheral blood mononudear cells were collected 2 to 3 times at 3- to 6-month intervals starting 40 to 109 months (mean, 64.2 +/- 18.5 months) after the end of therapy. In addition, lymphocyte and macrophage cultures were established at each point. In 11 patients, frozen liver tissue samples were available from follow-up biopsies performed 41 to 98 months (mean, 63.6 +/- 16.7 months) after therapy. Presence of HCV RNA was determined by sensitive reverse-transcriptase polymerase chain reaction, and concentration of positive and negative strands was determined by a novel quantitative real-time reverse transcriptase polymerase chain reaction. Only 2 of 17 patients remained consistently HCV RNA negative in all analyzed compartments. HCV RNA was detected in macrophages from 11 patients (65%) and in lymphocytes from 7 patients (41%). Viral sequences were also detected in 3 of 11 livers and in sera from 4 patients. Viral replicative forms were found in lymphocytes from 2 and in macrophages from 4 patients. In conclusion, our results suggest that in patients with SVR after therapy, small quantities of HCV RNA may persist in liver or macrophages and lymphocytes for up to 9 years. This continuous viral presence could result in persistence of humoral and cellular immunity for many years after therapy and could present a potential risk for infection reactivation.
authors.affiliation: Department of Medicine, Mayo Clinic Scottsdale, Scottsdale, AZ 85259, USA.
authors.forename: Marek
authors.initials: M
authors.lastname: Radkowski
authors.forename: Juan F
authors.initials: JF
authors.lastname: Gallegos-Orozco
authors.forename: Joanna
authors.initials: J
authors.lastname: Jablonska
authors.forename: Thomas V
authors.initials: TV
authors.lastname: Colby
authors.forename: Bozena
authors.initials: B
authors.lastname: Walewska-Zielecka
authors.forename: Joanna
authors.initials: J
authors.lastname: Kubicka
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Wilkinson
authors.forename: Debra
authors.initials: D
authors.lastname: Adair
authors.forename: Jorge
authors.initials: J
authors.lastname: Rakela
authors.forename: Tomasz
authors.initials: T
authors.lastname: Laskus
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism / Q000821:virology; D008214:Lymphocytes / Q000378:metabolism / Q000821:virology; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D012367:RNA, Viral / Q000097:blood / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012254:Ribavirin / Q000627:therapeutic use*; D013997:Time Factors; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral; D012254:Ribavirin; D007372:Interferons