Congreso Americano 2013-3

Study of the influence of HLA genetic factors on the vertical transmission and chronification of hepatitis C virus

Angeles Ruiz-Extremera 1,2,3, Esther-J. Pavón-Castillero4, Mónica Florido4, Paloma Muñoz-de-Rueda2,4, JoseAntonio Muñoz-Gámez4, Jorge Casado4, Angel Carazo4, Rosa Quiles2,4, Laura Sanjuan5, Sergio Jiménez-Ruiz5, Pepi León2,4, Javier Salmerón2,4,5

1 Pediatric Unit, Hospital Universitario San Cecilio, Granada, Spain  2 CIBER Enfermedades Hepáticas y Digestivas, CIBERehd, Instituto de Salud Carlos III, Spain  3 Pediatric Department, Granada University, Granada, Spain  4 Clinical Management Unit of Digestive Diseases, UNAI, Hospital Universitario San Cecilio, Granada, Spain  5 Medicine Department, Granada University, Granada, Spain

BACKGROUND:

Vertical transmission (VT) is considered the main route of hepatitis C virus (HCV) infection in children but the risk factors in this respect have yet to be fully identified, except maternal HIV co-infection. The aim of this study is to analyze the role of human leukocyte antigen (HLA) genetic factors in HCV-VT.

PATIENTS AND METHODS:

Between September 1991 and December 2009, 123 HCV-RNA positive (HIV negative) mothers were recruited, with their 130 children. The following risk factors for HCV were analyzed: HCV viral load, viral genotype, IL28B polymorphism (single nucleotide polymorphism rs12979860), delivery mode, ALT levels and breast-feeding. The infants were tested for HCV-RNA at birth, at 2, 4, 6, 8, 10, 12, 18 and 24 months, and then annually at 3, 4, 5 and 6 years. VT was defined as children who presented HCV-RNA positive for at least two subsequent blood samples. Chronic or persistent infection was defined as children with HCV-RNA positive at the end of the study. The frequencies of HLA class I alleles (A, B and Cw) and of HLA class II alleles (DRB1, DQA1, DQB1, DPA1 and DPB1) were analyzed.

RESULTS:

Of the 123 mothers (and 130 children) included in the study, VT occurred in 24 cases. Of these, 8 children suffered chronic infection and in 16 the virus was eliminated. VT study: Among the 123 mothers, the alleles related to VT were the presence of B*0702 (P=0.024), Cw*0702 (P=0.050) DQA1*0301 (P=0.011, Pc=0.04) and DPB1*0201 (P=0.046) and the absence of B*3501 (P=0.030) and Cw*0602 (P=0.006, Pc=0.05). Among the 130 children, however, the only allele related to VT was the presence of DPB1*0201 (P=0.038). Chronification of the virus: In this case, the associated alleles of the mothers (n=24) were DQA1*0101 (P=0.028) and

DQB1*0604 (P=0.028), and among the children (n=24) they were B*0801 (P=0.037), DRB1*0301 (P=0.037), DQA1*0501 (P=0.037) and DQB1*0603 (P=0.034). Mother/child allelic concordance was higher among the children with chronic infection than in those with no chronification (67% ± 4.06 vs. 57% ± 1.34, P=0.045).

CONCLUSIONS:

The HLA alleles of the mother are of greater importance than those of the child with respect to HCV-VT. Thus, the presence of the HLA allele, class I Cw*0602 and of the HLA allele, class II DQA1*0301 in the mother is directly related to VT. Moreover, the greater allelic concordance among the children, with respect to their mothers, is associated with the chronification of the virus in these children.

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