Elsevier

Journal of Hepatology

Volume 29, Issue 2, August 1998, Pages 207-213
Journal of Hepatology

Association between HLA class II genotype and spontaneous clearance of hepatitis C viraemia

https://doi.org/10.1016/S0168-8278(98)80005-6Get rights and content

Abstract

Background/Aims: Hepatitis C virus (HCV) infection becomes chronic in most cases, with only 10–20% of those infected not developing persistent viraemia. The immune response to HCV may be an important determinant of disease resolution and can be influenced by a number of host factors. The aim of this study was to assess the role of host HLA class II type in influencing viral clearance or susceptibility to chronic HCV infection.

Methods: We have compared the distribution of HLA DRB1, DQA1 and DQB1 alleles in 49 patients with spontaneous clearance of HCV infection (HCV antibody positive but persistently HCV RNA negative), with 55 chronically infected patients and 134 racially matched controls.

Results: Three alleles were found significantly more frequently in patients with spontaneous viral clearance compared to those with chronic infection-DRB1*04 (pc=0.0022, odds ratio OR= 4.52), DQA1*03 (pc= 0.0012, OR= 4.69) and DQB1*0301 (pc=0.0078, OR= 5.09). DQB1*0302 was found at reduced frequency in all HCV-antibody-positive patients compared to controls (pc=0.0063).

Conclusions: DRB1*04, DQA1*03 and DQB1*0301 are associated with spontaneous clearance of HCV viraemia, with the primary association likely to be with DQB1*0301 and the associations with DRB1*04 and DQA1*03 being due to linkage. In addition, DQB1*0302 is associated with protection from HCV infection. These findings suggest that host HLA class II genotype is an important factor in determining the outcome of infection with hepatitis C virus.

References (19)

There are more references available in the full text version of this article.

Cited by (160)

  • Trans-ancestral fine-mapping of MHC reveals key amino acids associated with spontaneous clearance of hepatitis C in HLA-DQβ1

    2022, American Journal of Human Genetics
    Citation Excerpt :

    This is a multi-site international consortium including multiple studies from Europe and United States in which HCV infection outcomes were ascertained. They include ALIVE (AIDS Link to the Intravenous Experience),18 BBAASH (Baltimore Before and After Acute Study of Hepatitis),19 BAHSTION (Boston Acute Hepatitis C Virus Study: Transmission, Immunity and Outcomes Network),13 Cramp and colleagues’ study,20 HGDS (Hemophilia Growth and Development Study),21 Mangia and colleagues’ study,22 MHCS (Multicenter Hemophilia Cohort Study) and MHCS-II,23 REVELL (Correlates of Resolved Versus Low-Level Viremic Hepatitis C Infection in Blood Donors) study,24 the Swan Project,25 the Toulouse, France cohort,15 WIHS (Women’s Interagency HIV Study),26 the United Kingdom Drug Use cohort,27 and the Urban Health Study (UHS)28,29 as described in detail in elsewhere.5,6,17 These studies were selected because they had well-established hepatitis C virus (HCV) outcomes, as previously described,5,6,17 available DNA, and IRB approval for genetic testing.

  • Modeling primary biliary cholangitis and primary sclerosing cholangitis as infectious diseases

    2022, Translational Autoimmunity: Challenges for Autoimmune Diseases: Volume 5
  • Immunogenetics in the diagnosis of clinical disorders

    2022, Immunogenetics: a Molecular and Clinical Overview: Clinical Applications of Immunogenetics, Volume II
  • IL-10 plays a central regulatory role in the cytokines induced by hepatitis C virus core protein and polyinosinic acid:polycytodylic acid

    2016, International Immunopharmacology
    Citation Excerpt :

    However, polyI:C acted synergistically with HCV core protein to induce secretion of IL-10 in the monocytes but inhibited HCV core protein-induced TNF-α and IL-1β secretion (Fig. 1). To further characterize the phenotypes of monocytes induced by HCV core protein or polyI:C, flow cytometry was used to determine phenotypic expression, including human leukocyte antigen-D related (HLA-DR), cluster of differentiation 38 (CD38), and programmed death-ligand 1 (PD-L1), which reflect the host's immune response [23,24] related to HCV persistence [25–32]. We found that the optimal concentrations of HCV core protein and polyI:C for induction were 10 μg/mL and 50 μg/mL, respectively, and that the number of dead cells became fewer on day 2, resulting in better phenotypic expression.

View all citing articles on Scopus
View full text