Hep B in the past and future

This insightful plenary session at the 9th Australasian Viral Hepatitis Conference began with Dr Dieter Glebe from Germany presenting on the origins of hepatitis B virus, a topic that rarely crops up in the clinic but is nonetheless fascinating.

Titled “Of bats and men: species specificity of hepadnaviral infection” Dr Glebe began by explaining the existing phylogenetic understanding of the virus in mammals which can be isolated in many species of non-human primates and also new world rodents such as woodchucks and ground squirrels. However, as the strains in the new world rodents cannot infect non-human primates and vice versa, Dr Glebe looked to bats, the mammalian viral mixing pot to investigate how the virus might have moved between rodents and non-human primates. He screened 3,080 bats from 54 species around the world, finding 10 animals PCR positive and a detection rate of 6-10% of hepadnaviral DNA in individual species. Most of the viruses were isolated from the liver.

The research then focused on assessing the zoonotic potential of these bat viruses. One strain isolated from a Panamanian tent making bat seemed to be the closest match to human virus and successfully replicated in human liver cells in vitro. Fortunately, the nucleoside analog entecavir was able to inhibit replication as with the human virus. However, and slightly worryingly, antisera from hepatitis B vaccinated humans was not protective against infection with the bat virus. Dr Glebe wrapped up the presentation with a charming picture of a non-human primate happily eating away at a bat, reminding us that nature often finds a way help species “mix”.

The second and final presentation of the session was titled “HBV Reactivation: Playing with fire” presented by Professor Maggie Bassendine from Newcastle, UK. Professor Bassendine began by reminding the audience that “resolved infection” is not immune clearance but immune control (as HBV cccDNA can still be found in some hepatocytes) and hence that control can be lost under certain circumstances. This reactivation can occur after receiving immunosuppressive therapy, such as chemotherapy or drugs associated with transplantation. Unfortunately it is not possible to predict whether reactivation will occur and how severe it will be, but some agents do seem to make it more likely. For instance, when chemotherapy was given with steroids, reactivation was more common than chemotherapy given without steroids. One of the newer agents used in cancer therapy, the monoclonal antibody Rituximab seems to be particularly associated with HBV reactivation with one paper recording it occurring in 1/20 patients with resolved HBV infection.

Professor Bassendine then discussed the role of screening for resolved HBV infection before giving patients immunosuppressive therapy noting the lack of consistency between HBV clinical guidelines which recommend screening, and oncology guidelines which don’t explicitly recommend screening, but leave it at the clinician’s digression. This is concerning as 20% of oncologists have been recorded never screening patients. Professor Bassendine then concluded the presentation by a making call for universal screening to be included across all national and local guidelines and suggesting the clinicians in the audience start by investigating the current screening practices in their own local hospitals.