New Hepatitis C Strains Could Harm World Eradication Goals

The recent discovery of 3 new strains of hepatitis C virus (HCV) genotype (GT) 7 in Africa, shortly after GT 8 was identified in India, pose challenges to attaining the World Health Organization (WHO) goal of eradicating HCV globally by 2030.

Manjinder Sandhu, PhD, Senior Group Leader, Wellcome Sanger Institute, Hinxton, Cabridgeshire, UK and a senior author of the study uncovering the new GT 7 subtypes, noted the strains had mutations associated with resistance to some direct-acting antivirals (DAAs), and called for increased clinical research in these under-resourced areas to facilitate development of effective interventions.

"Our study highlights the need for more investment on people in Africa and developing parts of the world," Sandhu said in a statement released at the time of the report. "We show there are clear differences in HCV across the world, underlining the need for understanding HCV globally."

In the largest population study of HCV in Africa to date, Sandhu and colleagues identified study candidates from a population-based survey, the Medical Research Council/Uganda Virus Research Institute (MRC/UVRI) General Population Cohort, which was taken in 2011. A cohort of 7751 participants from Uganda and 2 from the Democratic Republic of Congo (DRC) were screened for HCV, with 266 determined to be seropositive.

A nested case-control study was then formed with 565 participants, comprising 197 who were seropositive and a control group of 368 seronegative individuals. An additional antibody assay screen was administered, as well as HCV-RNA determination, to ascertain the accuracy and utility of the antibody assays for disease detection and to identify the diversity of the HCV genome in the region.

Sandhu and colleagues noted that approximately 11 million people in sub-Saharan Africa are currently affected, and the majority suffer from genotypes “that have received little or no attention in clinical treatment or vaccine trials, and it is likely that new genotypes remain undiscovered."

The HCV strains detected in the Uganda sampling included GT 4k, 4p, 4q, 4s in addition to a new, unassigned GT 7 subtype. The 2 samples from the DRC each yielded an additional unassigned GT 7 subtype. Sandhu and colleagues explained that a new, unassigned subtype strain can be declared when the open reading frames (ORFs) of the subtype differs from another by 10% to 25% at the nucleotide level, and a new GT, such as the GT 8 identified in India, when there is at least 30% difference.

The investigators found that detection of HCV seropositivity differed substantially between assay methods, which they suggest indicates there is an important role for molecular techniques to improve active infection detection. The HCV sequencing detected polymorphisms in the GT 4 and 7 strains, including NS3 and NS5A mutations associated with resistance to particular DAAs.

"Our work will help inform public health policy and reveals that further studies and clinical trials in sub-Saharan Africa are urgently needed if the WHO is to achieve its vision of eliminating hepatitis C by 2030," Sandhu said.

The study, "New Highly Diverse Hepatitis C Strains Detected in Sub-Saharan Africa have Unknown Susceptibility to Direct-Acting Antiviral Treatments," was published online in Hepatology.