The genotypes have a distinct geographical distribution and are used in tracing the evolution and transmission of the virus. Differences between genotypes affect the disease severity, course and likelihood of complications, and response to treatment and possibly vaccination. There are two other genotypes I and J but they are not universally accepted as of 2015. The diversity of genotypes is not shown equally in the world. For example, A, D, and E genotypes have been seen in Africa prevalently while B and C genotypes are observed in Asia as widespread.Genotypes differ by at least 8% of their sequence and were first reported in 1988 when six were initially described (A–F). Two further types have since been described (G and H). Most genotypes are now divided into subgenotypes with distinct properties. Mechanisms
Hepatitis B virus primarily interferes with the functions of the liver by replicating in hepatocytes. A functional receptor is NTCP. There is evidence that the receptor in the closely related duck hepatitis B virus is carboxypeptidase D. The virions bind to the host cell via the preS domain of the viral surface antigen and are subsequently internalized by endocytosis. HBV-preS-specific receptors are expressed primarily on hepatocytes; however, viral DNA and proteins have also been detected in extrahepatic sites, suggesting that cellular receptors for HBV may also exist on extrahepatic cells.During HBV infection, the host immune response causes both hepatocellular damage and viral clearance.
Adverse events
The most common adverse events reported in clinical studies were mild or moderate reactions involving the skin and appendages (primarily urticaria, rash, or pruritus), which occurred in 14 out of 42 patients. Three patients experienced a serious adverse event. Two patients had a severe allergic reaction (severe hives and a severe rash and pruritus) following treatment. One patient had a recurrent coagulopathy due to envenomation, which required re-hospitalisation and additional antivenin administration. In clinical trials, recurrent coagulopathy (the return of a coagulation abnormality after it has been successfully treated with antivenin), characterised by decreased fibrinogen, decreased platelets and elevated prothrombin time, occurred in approximately half of the patients studied. Recurrent coagulopathy may persist for one to two weeks or more. One patient discontinued CroFab therapy due to an allergic reaction. Patients with allergies to papain, chymopapain, other papaya extracts or the pineapple enzyme bromelain may also be at risk for an allergic reaction to CroFab. Cost
Leslie Boyer, Director of the VIPER Institute, who was on the team that developed CroFab, said they were "crestfallen" to discover that the wholesale price of Anascorp, their latest antivenom, was too high to be cost effective, even in the treatment of critically ill children. The industry website Fierce Pharma called the product a “drug launch disaster” and “one of the most bizarre marketing tales in the industry.” Boyer said that CroFab, a US drug whose sister product retailed in Mexico at $100, was resulting in bills to Arizona patients of between $7,900 and $39,652 per vial.