title: Interleukin-28B polymorphisms and interferon gamma inducible protein-10 serum levels in seronegative occult hepatitis C virus infection.
abstract: Polymorphisms upstream interleukin (IL)-28B gene and serum levels of interferon gamma inducible protein-10 (IP-10) are associated with spontaneous and treatment-induced hepatitis C virus (HCV) clearance. Patients with seronegative occult HCV infection are anti-HCV and serum HCV-RNA negative but have viral RNA in liver and abnormal values of liver enzymes. We examined if the rs12979860 polymorphism of IL-28B and serum IP-10 levels differ between chronic and seronegative occult CV infection. IL-28B polymorphism was determined with allele specific TaqMan probes in total DNA isolated from peripheral blood mononuclear cells and IP-10 by an enzyme-linked immunosorbent assay in serum from 99 patients with seronegative occult HCV infection and 130 untreated patients with chronic hepatitis C. IL-28B genotypes were also determined in 54 healthy volunteers. Prevalence of the IL-28B CC genotype was significantly higher in seronegative occult HCV infection (52/99; 52.5%) than in chronic hepatitis C (32/130; 24.6%, P < 0.0001) or healthy controls (19/54: 32.5%, P = 0.039). Among patients with seronegative occult HCV infection, HCV-RNA load in liver was significantly lower in those with the IL-28B CC genotype than in those with CT + TT genotypes (2.8 × 10(5)  ± 5.8 × 10(4) vs. 4.1 × 10(5)  ± 5.9 × 10(4)  copies/μg of total RNA respectively; P = 0.023). Mean serum IP-10 levels were significantly lower in patients with seronegative occult HCV infection than in patients with chronic hepatitis C (160.8 ± 17.9 vs. 288.7 ± 13.3 pg/ml respectively; P < 0.0001). These findings suggest that the host immune response plays an important role in seronegative occult HCV infection in comparison with chronic hepatitis C.
authors.affiliation: Fundación para el Estudio de las Hepatitis Virales, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Bartolomé
authors.affiliation: Fundación para el Estudio de las Hepatitis Virales, Madrid, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Castillo
authors.affiliation: Fundación para el Estudio de las Hepatitis Virales, Madrid, Spain.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Quiroga
authors.affiliation: Fundación para el Estudio de las Hepatitis Virales, Madrid, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Carreño
mesh_terms: D000328:Adult; D054357:Chemokine CXCL10 / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D060005:Genotyping Techniques; D006526:Hepatitis C / Q000473:pathology*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008099:Liver / Q000821:virology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D012189:Retrospective Studies; D044967:Serum / Q000737:chemistry* / Q000821:virology*; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D054357:Chemokine CXCL10; D007372:Interferons; D007378:Interleukins; D012367:RNA, Viral; C114753:CXCL10 protein, human; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: HCV; IL-28B; IP-10; occult infection