Impact of deletions and mutations in Hepatitis B virus envelope proteins on serological profile and clinical evolution

•HBV surface proteins play a key role in viral infectivity and host immune response.•PreS/S variants may occur spontaneously or under therapeutic pressure.•PreS variability promotes cirrhosis, hepatocarcinoma and acute exacerbations.•HBsAg/anti-HBs pattern is associated with mutations and deletions in preS/S gene.

The Hepatitis B virus (HBV) envelope glycoproteins are essential for viral entry into the hepatocyte and are also targets for host immune response. The study of these proteins could allow us to highlight molecular hot points influencing HBV fitness, which would subsequently modify the clinical evolution of the disease, both under anti-viral therapy or without treatment. The present short communication underlines the importance of the high variability in HBV envelope proteins, in regard with the literature and in our hands, for HBV-infected patients either on anti-HBV treatment or not. We report mutations in antigenic areas of S protein, i.e. CD8+/CD4+ T-cell epitopes and B-cell epitopes in the major hydrophilic region (MHR), such as sI126N and sG145R possibly involved in the rare coexisting Hepatitis B surface Antigen (HBsAg)/anti-HBs serological pattern. We mostly report serial mutations in preS region including preS1 deletion (aa 1-6, 31-71, 38-73, 72-104) and preS2 deletion (aa132-141) in patients with various clinical evolutions. Some of these viral envelope mutations, due to immune selection pressure, may result in a worsening of the hepatic disease.