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SCARB1 variants and HCV infection: Host susceptibility is lost in translation

  • Che C. Colpitts
    Correspondence
    Corresponding authors. Addresses: Inserm, U1110, 3 Rue Koeberlé, 67000 Strasbourg, France. Tel.: +33 3 68 85 37 03, fax: +33 3 68 85 37 24 (T.F. Baumert); Division of Infection and Immunity, University College London, 90 Gower Street, London WC1E 6BT, UK (C.C. Colpitts).
    Affiliations
    Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, 67000 Strasbourg, France

    Université de Strasbourg, 67000 Strasbourg, France

    Division of Infection and Immunity, University College London, London, UK
    Search for articles by this author
  • Thomas F. Baumert
    Correspondence
    Corresponding authors. Addresses: Inserm, U1110, 3 Rue Koeberlé, 67000 Strasbourg, France. Tel.: +33 3 68 85 37 03, fax: +33 3 68 85 37 24 (T.F. Baumert); Division of Infection and Immunity, University College London, 90 Gower Street, London WC1E 6BT, UK (C.C. Colpitts).
    Affiliations
    Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, 67000 Strasbourg, France

    Université de Strasbourg, 67000 Strasbourg, France

    Institut Hospitalo-Universitaire, Pôle Hépato-digestif, Hopitaux Universitaires de Strasbourg, 67000 Strasbourg, France
    Search for articles by this author
      Approximately 150 million people are chronically infected with hepatitis C virus (HCV). Despite the remarkable advancement of direct-acting antiviral agents (DAAs) in recent years, achieving high cure rates, HCV remains a major global health burden. In the absence of curative therapy, chronically infected individuals are at high risk of developing severe liver disease, including cirrhosis and hepatocellular carcinoma (HCC). Even viral cure does not eliminate the risk of HCC in all patients.
      • Baumert T.F.
      • Juhling F.
      • Ono A.
      • Hoshida Y.
      Hepatitis C-related hepatocellular carcinoma in the era of new generation antivirals.
      Approximately 25% of HCV-infected individuals spontaneously clear infection in the acute phase and do not go on to become chronically infected.
      • Hajarizadeh B.
      • Grebely J.
      • Dore G.J.
      Epidemiology and natural history of HCV infection.
      Furthermore, some intravenous drug users, who are frequently exposed to HCV over prolonged periods of time, appear to be protected from HCV re-infection.
      • Mizukoshi E.
      • Eisenbach C.
      • Edlin B.R.
      • Newton K.P.
      • Raghuraman S.
      • Weiler-Normann C.
      • et al.
      Hepatitis C virus (HCV)-specific immune responses of long-term injection drug users frequently exposed to HCV.
      These observations highlight that inter-person variability markedly affects the clinical course of HCV infection and liver disease. Indeed, genetic variation in interferon lambda 3 and interferon lambda 4 has been strongly associated with clearance of HCV infection and responsiveness to interferon-based therapies.
      • Thomas D.L.
      • Thio C.L.
      • Martin M.P.
      • Qi Y.
      • Ge D.
      • O'Huigin C.
      • et al.
      Genetic variation in IL28B and spontaneous clearance of hepatitis C virus.
      • Prokunina-Olsson L.
      • Muchmore B.
      • Tang W.
      • Pfeiffer R.M.
      • Park H.
      • Dickensheets H.
      • et al.
      A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus.
      However, the impact of genetic variation of host-dependency factors for HCV infection is still poorly understood. In this issue of Journal of Hepatology, Westhaus and colleagues address this question by examining whether genetic variants of a crucial HCV entry factor, scavenger receptor class B type I (SR-BI), influence HCV replication and clinical outcome.
      • Westhaus S.
      • Deest M.
      • Nguyen A.T.
      • Stanke F.
      • Heckl D.
      • Costa R.
      • et al.
      Scavenger receptor class B member 1 (SCARB1) variants modulate hepatitis C virus replication cycle and viral load.
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      Linked Article

      • Scavenger receptor class B member 1 (SCARB1) variants modulate hepatitis C virus replication cycle and viral load
        Journal of HepatologyVol. 67Issue 2
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          Today about 2% of the world population are chronically infected with the hepatitis C virus (HCV). Unless detected in time and treated successfully, chronic hepatitis C often leads to cirrhosis, hepatocellular carcinoma and the need for liver transplantation. Recently approved novel specific antiviral drugs have markedly increased the chances of curing infection. Nonetheless HCV infection remains a significant public health challenge and one of the main reasons for liver transplantation.1 Moreover, many aspects in the molecular interaction between this major pathogen and its human host remain to be fully understood.
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