Hepatitis C virus (HCV) infection is a global medicalproblem. The immune response to HCV is an importantdeterminant of disease evolution and can be influenced by varioushost factors. HLA class II may play an important role in immuneresponse against HCV. The association between HLA class IIantigen and HCV in different ethnic populations that has beenreported is controversial. Therefore the objective of the presentstudy was to determine the distribution of HLA class II DRB1alleles, to confirm the influence of these antigens on the outcomeof HCV infection and to assess the relationship between theseantigens with clinical , laboratory and histological state of the liveramong Egyptian children and adolescents with chronic HCVinfection . Methods: HLA class II DNA typing was performed bymeans of Hybridization with sequence specific oligonucleotideprobes, after amplification of the second exon of the DRB1 genesusing the RELI TM SSO HLA- DRB typing test. Forty six Egyptianpatients with chronic HCV infection were included in the study (29males and 17 females) with age range 3-17 years (10.4 years (y)±4.232); and 20 normal healthy control subjects. Results: HLADRB1*15 was found significantly with reduced frequency amongour cases when compared with controls (8.7%vs 45%) P<0.01.There were higher frequencies of HLA-DRB1*03, DRB1*04 andDRB1*13 in patients compared with controls (45.6, 39.1 and26.1%) respectively, indicating a possible implication of thesealleles with chronic HCV infection. There was no significantcorrelation upon comparing the frequency of these alleles withdemographic characteristics, risk factors of HCV acquisition, comorbidcondition, clinical presentation, abdominal ultrasonographicpicture, biochemical profile and histopathological examination inour patients.However; patients possessing the allele DRB1*03 wereencountered with significant reduced platelet count p=0.03 and thisallele was presented with high frequency in patients with minimalgrade of inflammation but it did not reach a statistical significancep=0.06, though it was very close. Patients with DRB1*04 hadsignificantly low serum albumin p=0.04 and patients with DRB1*13had a significant high serum AST levels p=0.05. These findingsagree with the association of these alleles and the development ofchronic HCV infection. Therefore, it can be concluded that the allele DRB1*15 isassociated with protection from chronic HCV infection and thealleles DRB1*03-*04 -*13 could be associated with chronic HCVinfection in Egyptian patients; However larger group of patients isneeded for statistical values to be more significant.