Hepatitis B virus infections are prevalent worldwide, but the outcomes of infection vary greatly from host to host. In many endemic regions, vertical transmission from mother to child is most common. In this transmission setting, virus genotype and shared patient genetics make for an interesting comparison of outcome of chronic hepatitis B infection. This case series demonstrates four family clusters which display disparate outcomes among family members with hepatitis B virus infections, further stressing the role of host and non-genetic factors in the natural history of the disease. Many host factors have been theorized, from epigenetic mechanisms to the role of chronic stress, but more research is needed to better understand those at higher risk of feared complications such as hepatocellular carcinoma and cirrhosis.