Roughly million people who are currently infected with HBV
Roughly 15 million people who are currently infected with HBV are co-infected with the hepatitis D virus (HDV) (WHO, 2017b). The superinfection not only leads to more severe liver damage and early onset of cirrhosis, but also to a higher mortality than HBV mono-infection (Rizzetto, 1983; WHO, 2017b). Epidemiological studies are scarce since usually HDV-infection is not monitored in standard laboratory diagnostics (WHO, 2017b). There is evidence that an epidemic occurred in Europe in the years between 1970 and 1990 and afterwards the prevalence diminished to a stable percentage (Rizzetto, 2009). Data show that migrants from highly HBV/HDV-endemic countries often convey the infection, resulting in a stagnant decline of the infection (Rizzetto, 2009).
Recently, the European Association for the Study of the Liver (EASL) has published its new guidelines for the diagnosis and treatment of HBV. The aim of this review is to summarize changes in diagnostics and classification in HBV/HDV as well as to pay particular attention to new drug candidates in clinical trials (EASL, 2017).
Viral structure, lifecycle and transmission
Diagnosis and current therapy
Selection of strategies in clinical trials against HBV or HDV infections Drug candidates in recent clinical trials cover a wide range of approaches to inhibit the spread of HBV/HDV. While every new target deserves its place and has consumed years of research, only a few can be covered in detail in this review. The authors focused on substances which target proteins or Raltegravir rather than viral transcripts, such as RNA (Fig. 2, Table 3). Also the substance AT-130 has been added due to its significance in research and literature.
Introduction Since the discovery of the Australia antigen in 1963 , hepatitis B surface antigen (HBsAg), which was the first identified protein of the hepatitis B virus (HBV), has become one of the most important biological and serological indicators for the diagnosis of HBV infection . With continuous advances and improvement in detection methods and technology, the sensitivity and accuracy of quantitative HBsAg detection has significantly improved, and the application of the results of HBsAg detection has become more extensive. Quantitative HBsAg measurement can be used to clinically diagnose the disease, evaluate the disease stage , , , , , , examine the history of HBV infection , , , perform risk assessment in cases of chronic hepatitis B virus (CHBV) infection progression and liver cirrhosis, diagnose liver cancer and liver cancer recurrence , ,  and evaluate the efficacy of treatment for HBV infection , . HBsAg is the main protein generated in hepatocytes by HBV and is secreted into the blood. HBsAg consists of three structural proteins [large hepatitis B (LHBs), intermediate hepatitis B (MHBs) and small hepatitis B surface (SHBs) antigen], which are all encoded in the HBV pre-S/S open reading frame. SHBs consists of 226 amino acids, MHBs is identical to SHBs but contains 55 additional amino acids at the N-terminus, and LHBs is an extension of MHBs that contains 108–109 additional amino acids , . The domain-flanking amino acid residues 99–169 in SHBs constitute the main hydrophilic region (MHR) of HBsAg. Within this region, the fragment corresponding to amino acid residues 124–147 is located in loop2 and forms the “a” antigenic determinant of HBsAg, which is the major antigenic determinant of the vaccine; this determinant elicits the formation of protective antibodies and is important for antibody identification and binding using commercial kits , , , . The concentration of HBsAg in the serum of HBV-infected patients depends both on the expression of the corresponding encoded mRNA and on the establishment of a complex equilibrium involving the interaction between HBV and the host immune system, not simply on the viral replication process , , , . During the natural process of HBV infection, a population with HBV infection characterized by a sustained low level of HBsAg in serum is formed. Studies have confirmed the presence of a population with low-level HBsAg in serum and low HBV DNA replication; these subjects are mostly chronic asymptomatic HBV carriers (ASCs) , , , , , , . This poses a new challenge for the prevention and treatment of hepatitis B and has received widespread attention from clinicians, laboratory diagnostic specialists, epidemiologists and molecular biologists , . To date, few studies have investigated the mechanism underlying the sustained low-level HBsAg expression in ASCs. Therefore, we sequenced the S gene of chronic ASCs with sustained low-level HBsAg expression and compared these sequences with the established S gene sequences of chronic ASCs with sustained high-level HBsAg expression to reveal the characteristics of the S gene sequences and explore the mechanism underlying the sustained low-level HBsAg expression in these patients.