The natural history of human HBV infection varies between the different genotypes [25], as the predominant mode of transmission, the timing of the Hepatitis B e antigen (HBeAg) seroconversion to the hepatitis B e antibody (anti-HBe), the progression of liver-associated diseases—including Hepatocellular Carcinoma (HCC), and the potential of Hepatitis B surface antigen (HBsAg) seroclearance, vary substantially Box 1 [38]. The gene discussed is HBE1; the disease is hepatocellular carcinoma.