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Long-term follow-up of successful hepatitis C virus therapy: waning immune responses and disappearance of liver disease are consistent with cure.
Karolinska Universitetssjukhuset Huddinge, Stockholm.
Karolinska Universitetssjukhuset Huddinge, Stockholm.
Karolinska Institutet, Stockholm .
Twincore Centre for Experimental and Clinical Infection Research, Hannover, Germany.
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2015 (English)In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 41, no 6, 532-543 p.Article in journal (Refereed) Published
Abstract [en]

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.

AIM: 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.

Place, publisher, year, edition, pages
2015. Vol. 41, no 6, 532-543 p.
National Category
Infectious Medicine
URN: urn:nbn:se:liu:diva-113807DOI: 10.1111/apt.13096ISI: 000349617000003PubMedID: 25627143OAI: diva2:784810

EDB was supported by grants from the Swedish Society for Medical Research, the Ruth and Richard Julin Foundation, the Professor Nanna Svartz Fund, the Ake Wiberg Foundation, the Clas Groschinsky Memorial Foundation, the Goljes Memorial Fund, the Lars Hierta Memorial Foundation, the Erik and Edith Fernstrom Foundation and from Karolinska Institutet. MS was supported by the Swedish Cancer Society, the Swedish Research Council, the Stockholm County Council and Vinnova. OW was funded by Schering-Plough and MSD. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Available from: 2015-01-30 Created: 2015-01-30 Last updated: 2016-03-29

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Cardell, KristinaFrydén, Aril
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Division of Microbiology and Molecular MedicineFaculty of Medicine and Health SciencesDepartment of Infectious Diseases
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