The Role of Host in the Spectrum of Outcomes in Family Clusters of Hepatitis Infection: From Asymptomatic to Hepatocellular Carcinoma

Abstract

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.

Review of Related Factors for Persistent Risk of Hepatitis B Virus-Associated Hepatocellular Carcinoma

“…Furthermore, one of the families had monozygotic twins in which only one sibling developed HBV-related HCC, while the other remained a chronic HBV carrier. The same finding is presenting in a case series by Noverati et al, which presented four family clusters in which patients had very variable courses, some with indolent chronic HBV infection, some requiring treatment, and others who developed HCC or cirrhosis [65]. It is postulated that inheritable immuno-genetic alleles that affect CHB differ from those that influence HBV-related HCC development, which may explain the discrepancy in manifestations in this case series [66].…”

Chronic Hepatitis B: A Summarized Anecdote of Complexities in Natural History, Treatment, and Complications

“…It has been our overall observation that despite the assumed similar genetic makeup of virus and similar genetics within families, outcomes of CHB can still vary greatly. For example, in a family with identical twin sons who were infected at birth from their mother, one twin developed HCC, while the other remained asymptomatic and symptom-free for years, as shown in Figure 1 [4]. The twin with the less desirable outcome had greater levels of stress in his life, and may have had exposure to other environmental toxins, such as alcohol.…”