title: Long-term follow-up of successful hepatitis C virus therapy: waning immune responses and disappearance of liver disease are consistent with cure.
abstract: BACKGROUND
  A sustained viral response (SVR) after interferon-based therapy of chronic hepatitis C virus (HCV) infection is regarded to represent a cure. Previous studies have used different markers to clarify whether an SVR truly represents a cure, but no study has combined a clinical work-up with highly sensitive HCV RNA detection, and the determination of immune responses.
  
  
  OBJECTIVE
  To determine clinical, histological, virological and immunological markers 5-20 years after SVR.
  
  
  METHODS
  In 54 patients, liver biochemistry, histology and elastography were evaluated. Liver biopsies, plasma and peripheral blood mononuclear cells (PBMCs) were tested for minute amounts of HCV RNA. HCV-specific T-cell responses were monitored by ELISpot and pentamer staining, and humoral responses by measuring HCV nonstructural (NS)3-specific antibodies and virus neutralisation.
  
  
  RESULTS
  Liver disease regressed significantly in all patients, and 51 were HCV RNA-negative in all tissues tested. There was an inverse association between liver disease, HCV-specific T-cell responses and HCV antibody levels with time from SVR, supporting that the virus had been cleared. The three patients, who all lacked signs of liver disease, had HCV RNA in PBMCs 5-9 years after SVR. All three had HCV-specific T cells and NS3 antibodies, but no cross-neutralising antibodies.
  
  
  CONCLUSIONS
  Our combined data confirm that a SVR corresponds to a long-term clinical cure. The waning immune responses support the disappearance of the antigenic stimulus. Transient HCV RNA traces may be detected in some patients up to 9 years after SVR, but no marker associates this with an increased risk for liver disease.
authors: Department of Infectious Diseases, Karolinska University Hospital Huddinge, Stockholm, Sweden; Division of Infectious Diseases, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors: M
authors: M
authors: Hedenstierna
authors: O
authors: O
authors: Weiland
authors: A
authors: A
authors: Brass
authors: D
authors: D
authors: Bankwitz
authors: P
authors: P
authors: Behrendt
authors: I
authors: I
authors: Uhnoo
authors: S
authors: S
authors: Aleman
authors: K
authors: K
authors: Cardell
authors: A
authors: A
authors: Fryden
authors: G
authors: G
authors: Norkrans
authors: A
authors: A
authors: Eilard
authors: H
authors: H
authors: Glaumann
authors: T
authors: T
authors: Pietschmann
authors: M
authors: M
authors: Sällberg
authors: E D
authors: ED
authors: Brenndörfer
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D018937:Hepatitis C Antibodies; D012367:RNA, Viral