Hepatitis B virus can be directly cytopathic to hepatocytes. Nevertheless, the immune system– mediated cytotoxicity largely contributes to liver damage. The human leukocyte antigen (HLA) class I–restricted CD8 cytotoxic T lymphocytes that identify the HBeAg and HBcAg on the cell membranes of disease-ridden hepatocytes drives the immune attack (Nelson et al., 2016). In the first stage of infection, the HBV virions attach to liver cells (hepatocytes) then penetrate the hepatocyte’s cytoplasm (Oakes, 2014). The HBV virions are uncoated, which implies that nucleocapsids can move into the hepatocytes’ nuclei and change the DNA to covalently closed circular DNAs (cccDNAs) (double-stranded DNA structures). The cccDNAs are very stable and can stay in the hosts’ nuclei for many months in chronic illness. The virus replicates itself in a process, which does not have “proofreading ability" that permits the virus to undergo mutation (Oakes, 2014). The newly created HBV virions are released into the bloodstreams, from where they attack other hepatocytes and repeat the replication process. I think the HBV leads to progressive fibrosis and inflammation in the infected liver by initiating the immune system to assault the hepatocytes. Natural History of HBV 30-180 days is the incubation period for HBV (Oakes, 2014). The ages at which individuals are infected with the HBVs determine the disease outcomes; 90% of those who are infected by HBV in early childhood or perinatal stage will develop Chronic Hepatitis B, as their immunity is already compromised and cannot clear or terminate infected hepatocytes. In adults, 90% of infected people develop acute Hepatitis B and only 5 to 10% grow into Chronic Hepatitis B. Acute liver failure happens in 1% of acute Hepatitis B cases. It is rare (in 1-2% of cases) for individuals with Chronic Hepatitis B to lose the HB Virus surface antigens that are thought to be definitive recovery (Nelson et al., 2016). Nevertheless, the virus reactivates when they become immunosuppressed. Progression of HBV The rate of HB disease progression is affected by several factors. Stages are related to the extent of Hepatitis B virus replication and the way the immune system responds. Immune-tolerant phase takes 10-30 years if the HBV was acquired in the perinatal stage but has a shorter duration or does not exist for people who were infected as adults or children (Oakes, 2014). Immune clearance phase (immuno-active) has people who are infected with the virus in adolescence, adulthood, or late childhood. When people lose the immunotolerability, the immune system assaults the infected hepatocytes, causing changing HBV DNA levels and high ALT levels, and liver fibrosis (Nelson et al., 2016). Inactive carrier phase (immune control) is an inactive stage of HBeAg negative Hepatitis B virus with undetectable or low HBV DNA levels, no damage to the liver and a normal ALT. Reactivation phase can be spontaneous or can be initiated by immunosuppression. Infected people can revert to HBeAg positivity, but a majority are an HBeAg negative with detectable DNA levels, moderate to severe necro-inflammation and high ALT with variable amounts of fibrosis on liver biopsy (Nelson et al., 2016). Public Health Considerations Disease is usually asymptomatic in infants and is often mild in children. Some of the medicines used to manage this condition have negative side effects to the patients. Therefore, the patients’ health status such as pregnancy or existing diseases must be considered before prescribing some of these drugs. Since Smith has diabetes mellitus, I believe she is immunocompromised, and her antibody rate was slow. Therefore, she needs the boosters to support her immunity. References Oakes, K., 2014. Hepatitis B: prevalence and pathophysiology. Nursing times, 110(7), pp.12-16. Nelson, N.P., Easterbrook, P.J. and McMahon, B.J., 2016. Epidemiology of hepatitis B virus infection and impact of vaccination on a disease. Clinics in liver disease, 20(4), pp.607- 628.