Prevalence of mixed genotype hepatitis C virus infections in the UK as determined by genotype‐specific PCR and deep sequencing

Abstract

SummaryThe incidence of mixed genotype hepatitis C virus (HCV) infections in the UK is largely unknown. As the efficacy of direct‐acting antivirals is variable across different genotypes, treatment regimens are tailored to the infecting genotype, which may pose issues for the treatment of underlying genotypes within undiagnosed mixed genotype HCV infections. There is therefore a need to accurately diagnose mixed genotype infections prior to treatment. PCR‐based diagnostic tools were developed to screen for the occurrence of mixed genotype infections caused by the most common UK genotypes, 1a and 3, in a cohort of 506 individuals diagnosed with either of these genotypes. The overall prevalence rate of mixed infection was 3.8%; however, this rate was unevenly distributed, with 6.7% of individuals diagnosed with genotype 3 harbouring genotype 1a strains and only 0.8% of samples from genotype 1a patients harbouring genotype 3 (P < .05). Mixed infection samples consisted of a major and a minor genotype, with the latter constituting less than 21% of the total viral load and, in 67% of cases, less than 1% of the viral load. Analysis of a subset of the cohort by Illumina PCR next‐generation sequencing resulted in a much greater incidence rate than obtained by PCR. This may have occurred due to the nonquantitative nature of the technique and despite the designation of false‐positive thresholds based on negative controls.

Safety and efficacy of combined sofosbuvir/daclatasvir treatment of children and adolescents with chronic hepatitis C Genotype 4

“…Twenty‐eight per cent of our patients were unique and notable due to their mixed genotype, either having GT‐4 and 1a (13%) or GT‐4 and 1b (15%) (Table ). The presence of mixed genotypes is a globally rare phenomenon that is not frequently documented in the literature . Due to the repeated potential for HCV exposure, intravenous drug users and haemodialysis patients are believed to be at higher risk of contracting mixed genotype infections than the general population .…”

The Prevalence of Mixed Hepatitis C Virus Genotype Infection and Its Effect on the Response to Direct-Acting Antivirals Therapy

“…It is well recognized that the prevalence of mixed genotype is higher in patients with repeated HCV exposures, such as patients on hemodialysis, intravenous drug users, and patients who received multiple transfusions, as compared with those with chronic hepatitis without the risk of repeated HCV exposures [8, 10, 13]. This study excluded patients co-infected with HIV and hemophiliacs because these groups have a higher possibility of infection with genotypes other than 1 and 2.…”

“…Consequently, the combination of genotyping with specific primers and direct sequencing should be developed according to this unique distribution. For example, a report from Scotland screened patients for genotypes 1a and 3 for mixed genotype infection because these genotypes comprise over 90% of the genotypes in the UK [13]. This combination method of detecting mixed genotype is expensive, labor intense, and time consuming.…”

“…Taking this into consideration, we only focused on genotypes 1 and 2 as the used combination of direct sequencing was able to detect mixed genotype 1 and 2. The prevalence of HCV genotypes follows a unique distribution [7, 13, 18]. Consequently, the combination of genotyping with specific primers and direct sequencing should be developed according to this unique distribution.…”

“…Mixed infection can be defined as the detection of more than 2 genetically distinct HCV strains simultaneously [8]. The prevalence and incidence of mixed HCV genotype infection are variable, with only a few reports regarding the efficacy of direct-acting antivirals (DAA) therapy in patients with mixed HCV genotype infection [9-13]. We aimed to investigate the prevalence of mixed HCV genotype infection in Japanese patients and its impact on virologic response to DAA therapy.…”