Hepatitis C virus (HCV) genotype (GT) distribution and frequency were studied among 22,407 unique specimens tested at a national reference testing laboratory. Subjects with HCV GT 3 were younger (P < 0.0001) than those with GT 1, 2, or 4, and the regional frequencies of HCV GT 2 and 3 ranged from 19.9% to 29.2%.Based on sequence divergence throughout its genome, hepatitis C virus (HCV) is currently classified into six major genotypes or clades (1 to 6), with more than 70 confirmed or provisional subtypes identified (19). HCV genotype (GT) determination is an important tool in the clinical management of chronic HCV infection due to its usefulness in predicting the likelihood of treatment response and determining the optimal duration of treatment with existing anti-HCV combination therapy (pegylated alpha interferon and ribavirin) (11). In general, HCV GT 1 and 4 are less likely to respond to current anti-HCV therapy and typically require a longer duration of treatment than GT 2 and 3. Optimal duration of therapy and response rates for HCV GT 5 and 6 remain unclear due to relatively low occurrence of these genotypes in most developed countries. As directly acting antiviral agents are introduced as adjunct anti-HCV therapy for HCV GT 1 infection, reliable differentiation of HCV subtypes 1a and 1b will likely become important for assessing the likelihood of evolving drug resistance and ultimate treatment failure among patients undergoing anti-HCV therapy (18).Previous studies of HCV GT distribution and frequency have identified HCV GT 1 as the most common GT in the United States, followed by GT 2 and 3 (2, 6, 13-15, 20, 22). However, along with evolving modes of transmission, immigration and greater cultural diversity have the potential to impact directly HCV epidemiology and could result in increased frequencies of previously uncommon HCV GT 4, 5, and 6 in the United States (3, 15). Unfortunately, most of these earlier studies conducted in the United States were performed more than a decade ago, consisted of relatively small numbers of subjects, or focused on specific subpopulations. To address this lack of current data, we retrospectively analyzed data from a large cohort of clinical specimens originating in the United States and recently submitted to a national reference testing laboratory for GT determination. Our objective was to study HCV GT distribution and frequency among these referred clinical specimens in relation to all available subject information, including the subject's age and gender and the regional origin of the specimen.Data from 22,407 consecutive, unique clinical serum specimens originating from 647 laboratories (mean of 34.6 specimens per laboratory; maximum of 517 specimens from a single laboratory) located throughout the United States and submitted to Mayo Medical Laboratories, Rochester, MN, for routine pretreatment HCV GT determination over a 24-month period
