diagnostic and therapeutic implications in a case of mixed hepatitis c virus (hcv) infection

Introduction: hepatitis c virus (hcv) multiple infections can influence the course of the disease, either by boosting hepatocellular injury or by increasing the frequency of exacerbations. their prevalence ranges from 5% to 39% in individuals with hcv infection, with a higher impact on injection drug users (idus), or in prison settings. case presentation: the current paper reported a case of dualhcvinfection in a 31-year-old female, with a referred vertical transmission of hcv infection and also a history of idu, who harbored a subtype 4d since youth. treatment failure, after a 24-week course of sofosbuvir/ledipasvir, prompted a reevaluation of present and past hcv status. hcv genotype was determined by inno-lipatm hcv ii kit (lipa ii) (innogenetics, ghent, belgium) and sequencing of ns5b region (nucleotide 8281 - 8679). direct-acting antivirals (daas) resistance profile was investigated by ns3/4, ns5a and ns5b sequencing with specific primers. the sentosa® sq next generation sequencing (ngs) workflow was further performed in the baseline and failure samples. unexpectedly, a subtype 4d in the pretreatment sample and a subtype 1a in the posttreatment were identified. no resistance associated mutations (ras) were detected in the subtype 4d, although the 170av and 174s in the ns3/4 gene, the 30r in the ns5a gene, and the 444d in the ns5b gene were detected in the subtype 1a virus from the failure sample. conclusions: two main hypotheses were raised: a reinfection with a new subtype 1a virus during the treatment with a wild type strain, which developed ras after infection or with an already mutated virus; and a pretreatment hidden dual subtype 4d plus 1a infection.