Speculatively, because of the constant production of SP1 variants and thus HBSP regardless of the levels of replication, genotypes B and C will likely cause more severe cellular damage than A, D or E, thus resulting in increased risk of HCC development consistent with previous reports that B and C were associated with more severe disease23,24 and were more oncogenic20,25–28. The gene discussed is SP1; the disease is hepatocellular carcinoma.