During hepatitis C virus (HCV) infection,broadly neutralizing antibody (bNAb) responses targeting E1E2 envelope glyco proteins are generated in many individuals.It is unclear if these antibodies play a protective or a pathogenic role during chronic infection. In this study, we investigated whether bNAb responses inindividuals with chronic infection we reassociated with differences in clinical presentation. Patient-derived purified serum IgG was used to assess the breadth of HCV E1E2 binding and the neutralization activity of HCV pseudoparticles. The binding and neutralization activity results for two panels bearing viral envelope proteins representing either an intergenotype or an intragenotype 1 group were compared. We found that the HCV load was negatively associated with srong cross-genotypic E1E2 binding (P=0.03). Overall,we observed only a modest correlation between total E1E2 binding and neutralization ability. The breadth of intergeno type neutralization did not correlate with any clinical parameters;however,analysis of individuals with genotype1(gt1) HCVinfection(n=20),using an intrageno type pseudop article panel,found a stronga ssociation between neutralization breadth and reduced liver fibrosis(P=0.006).Abroad bNAb response in our cohort with chronic infection was associated with a single nucleotide polymorphism (SNP) in the HLA DQB1 gene (P=0.038),as previously reported in a cohort with acute disease. Furthermore,the bNAbs in these individuals targeted more than one region of E2-neutralizing epitopes, as assessed through cross-competition of patient bNAbs with well-characterized E2 antibodies. We conclude that the bNAb responses inpatients with chronic gt1 infection are associated with lower rates of fibrosis and host genetics may play a role in the ability to raise such responses.