Behavior of soluble HLA-A, -B, -C and HLA-G molecules in patients with chronic hepatitis C virus infection undergoing pegylated interferon-α and ribavirin treatment: potential role as markers of response to antiviral therapy

Clin Exp Med. 2017 Feb;17(1):93-100. doi: 10.1007/s10238-015-0399-5. Epub 2015 Nov 14.

Abstract

The serum levels of soluble HLA class I antigens (sHLA-A, -B, -C and sHLA-G) were determined in 40 HCV genotype 1-infected patients before (T 0), after 3, 6, and 12 months (T 3, T 6, and T 12) of pegylated-IFN-α plus ribavirin therapy and 6 months (T 18) after the end of treatment. Twenty patients were sustained virological responders (SVR), and 20 were non-responders (NR). sHLA-A, -B, -C levels at T 0 were significantly higher in both SVR (mean 10.48 μg/ml) and NR (mean 11.87 μg/ml) patients as compared to healthy controls (mean 0.34 μg/ml, p < 0.0001) and HIV-infected subjects (mean 1.22 μg/ml, p < 0.0001). sHLA-G levels at T 0 were significantly higher in SVR (mean 24.78 ng/ml) and NR (mean 24.93 ng/ml) patients as compared to healthy controls (mean 10.34 ng/ml, p = 0.015 and p = 0.014, respectively) but were lower as compared to HIV-infected subjects (mean 48.00 ng/ml, p < 0.0001). The levels of sHLA-A, -B, -C and sHLA-G significantly decreased in SVR from T 0 to T 18 (mean 1.64 and 1.43 ng/ml, respectively, p < 0.0001) and correlated with HCV-RNA, AST, ALT, γGT, and ALP levels. The determination of soluble HLA class I levels could be proposed as a surrogate marker to discriminate SVR and NR HCV-infected patients during PEG-IFN-α plus ribavirin therapy.

Keywords: HCV; HLA-G; Interferon-α; Ribavirin; Soluble HLA.

MeSH terms

  • Adult
  • Alanine Transaminase / blood
  • Antiviral Agents / therapeutic use*
  • Aspartate Aminotransferases / blood
  • Biomarkers, Pharmacological / blood*
  • Coinfection
  • Drug Therapy, Combination
  • Female
  • Gene Expression
  • HIV / drug effects
  • HIV / physiology
  • HIV Infections / drug therapy
  • HIV Infections / genetics
  • HIV Infections / immunology
  • HIV Infections / virology
  • HLA-A Antigens / blood
  • HLA-A Antigens / genetics
  • HLA-A Antigens / immunology
  • HLA-B Antigens / blood
  • HLA-B Antigens / genetics
  • HLA-B Antigens / immunology
  • HLA-C Antigens / blood
  • HLA-C Antigens / genetics
  • HLA-C Antigens / immunology
  • HLA-G Antigens / blood
  • HLA-G Antigens / genetics
  • HLA-G Antigens / immunology
  • Hepacivirus / drug effects
  • Hepacivirus / physiology
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics
  • Hepatitis C, Chronic / immunology
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Male
  • Middle Aged
  • Polyethylene Glycols / therapeutic use*
  • RNA, Viral / antagonists & inhibitors*
  • RNA, Viral / biosynthesis
  • Recombinant Proteins / therapeutic use
  • Ribavirin / therapeutic use*
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Biomarkers, Pharmacological
  • HLA-A Antigens
  • HLA-B Antigens
  • HLA-C Antigens
  • HLA-G Antigens
  • Interferon alpha-2
  • Interferon-alpha
  • RNA, Viral
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • peginterferon alfa-2b