Genetic associations in chronic hepatitis B infection: toward developing polygenic risk scores

Chronic hepatitis B (CHB) infection results in multiple clinical phenotypes of varying severity. One of the critical gaps in CHB management is the lack of a genetic-based tool to aid existing hepatocellular carcinoma and cirrhosis risk stratification models for patients with active CHB. Such individual predictive models for CHB are plagued by an inherent limitation of discriminatory power that clearly indicates the need for their improvement. In this article, we highlight genetic association studies in CHB that identified HLA and cytokine genetic susceptibility loci to CHB. We advance the position that translating CHB genetic susceptibility loci into polygenic risk scores will be a welcome addendum to the current arsenal of CHB outcome predictive models. We conclude with comments on hurdles that future research efforts should address within the research enclave of CHB and advocate for increased genetic data representation from sub-Saharan Africa.