Hepatitis B virus (HBV) is a member of the hepadnavirus family. Hepadnaviruses can be found in both mammals (orthohepadnaviruses) and birds (avihepadnaviruses). The genetic variability of HBV is very high. There are eight genotypes of HBV and three clades of HBV isolates from apes that appear to be additional genotypes of HBV. Most genotypes are now divided into subgenotypes with distinct virological and epidemiological properties. In addition, recombination among HBV genotypes increases the variability of HBV. This review summarises current knowledge of the epidemiology of genetic variability in hepadnaviruses and, due to rapid progress in the field, updates several recent reviews on HBV genotypes and subgenotypes.

Hepatitis B Virus (HBV) genotypes have come of age. The concept that HBV genotypes may influence the course of disease and relevant biological differences has now been recognised. However, there are still major gaps in our knowledge. Most clinical data come from Asia and describe findings in patients infected with genotypes B and C. Large scale studies with genotypes A and D as found in Europe or A, D and E from Africa are urgently needed to broaden our understanding. Experimental data which explain in vivo findings in terms of differences in molecular biology in vitro are still in the beginning. The succeeding years will see many interesting studies which will aid our understanding of how variants and genotypes of HBV influence the spectrum of disease in people infected with HBV.

There are eight genotypes of HBV designated A to H based on greater than 8% nucleotide variation over the entire genome. Hepadnaviruses infecting primates like the chimpanzee, orangutan and gibbon are very similar and can be regarded as genotypes of HBV. The eight genotypes of HBV show a distinct geographical distribution and influence the course of disease and the prognosis of treatment. Due to the variability of HBV, diagnostic procedures risk giving false-negative results or reporting an inaccurately low quantitative result. Thus, the variability of HBV genotypes can influence the interpretation of diagnostic data and the therapeutic decisions thereof in an unwanted way. HBV genotypes differ in the length of their genomes. The old system of numbering HBV nucleotides from the start of a non-conserved EcoRI site in the genome leads to difficulties in comparing nucleotide positions between genotypes. A numbering system is presented which avoids this problem. In addition we discuss the currently available methods for genotyping HBV.

Persistent infection by hepatitis B virus (HBV) is epidemiologically correlated with the prevalence of hepatocellular carcinoma, but its role in tumor development is not yet understood. To study the putative oncogenic potential of HBV, a non‐malignant immortal mouse hepatocyte line FMH202 harboring metallothionein promoter‐driven simian virus 40 large tumor antigen was transfected with HBV DNA. All stably transfected clones which replicated HBV displayed malignant growth characteristics in soft agar and were tumorigenic upon inoculation in nude mice. The nude mice tumors were histologically classified as differentiated or anaplastic hepatocellular carcinomas. As with human liver carcinomas, rearrangements of in vitro integrated HBV sequences were observed in the nude mouse tumors, and in tumor‐derived cell lines. In one case, expression of viral core and surface antigens was blocked in the tumors, correlating with hypermethylation of the HBV genome. However, the expression of X gene was maintained in most tumors and tumor‐derived cell lines. X protein was detected in nuclei by immune fluorescence and by immune blot. These results provide the first demonstration that HBV displays oncogenic potential in an experimental system. This system could be useful to functionally identify HBV genes which convey a tumorigenic phenotype.

No abstract

Background and aims:The major risk factors for acute hepatitis B (AHB) in China and the viral factors determining the progression from acute to chronic hepatitis B remain largely unknown.Methods:Epidemiological studies within a population-based surveillance for AHB in adults were performed in Shanghai, China, including 294 patients, 588 matched controls and 572 family members of the patients.Results:Invasive medical procedures, household contact with hepatitis B virus (HBV) carriers, body care and beauty treatments, and lack of HBV vaccination were independently associated with AHB. Among those risks, pedicure in bath centres emerged. Sixty-eight of 128 patients with AHB were genotyped including 33 with HBV B2 and 35 with HBV C2. Twenty-five (8.50%) of the 294 patients, including 20 with HBV C2 and 5 with HBV B2 (p = 0.013), progressed to chronic infection. Multivariate analysis showed that HBV C2 was independently associated with chronicification of AHB. Patients with HBV B2 were younger and there was a higher proportion of women than those with HBV C2. The prevalence of HBV B2 was higher in the patients than in neighbourhood chronic carriers. The chronic carriers with HBV B2 showed higher viral loads, higher hepatitis B e antigen (HBeAg) seropositivity, and with higher proportion in men than those with HBV C2, implying that sexual contact plays a role in the transmission of HBV B2. Phylogenetic analysis showed that HBV C2 was frequently involved in transmissions within households.Conclusions:Despite lower viral load and HBeAg status in the chronic carriers, HBV C2 was more prone to causing chronic infection than was HBV B2.

Introduction: Hepatitis B virus (HBV) genotypes, replication status, and mutations have been associated with the risk of hepatocellular carcinoma (HCC). Our aim was to study the distribution and HCC-related viral properties of HBV genotypes/subgenotypes in Mainland China.Methods: A multistage cluster probability sampling method was applied to select 81,775 participants between 1 and 59 years at 160 national disease surveillance points. We examined hepatitis B surface antigen, HBV genotypes and subgenotypes, hepatitis B e antigen, viral load, and mutations in the PreS and core promoter regions of HBV genome.Results: HBV subgenotypes B2 (27.3%), C1 (10.7%), and C2 (58.0%) were predominant. Genotype D (D1, 80.8%) was frequent in the Uygur. We identified a new subgenotype, C9, mainly in Tibetans. Compositions of subgenotypes B2 and C1 and genotype mixture increased from the North to Central South, which was consistently associated with the increasing prevalence of hepatitis B surface antigen. Hepatitis B e antigen positivity and viral loads were higher in the young with genotype B and declined more rapidly with increasing age than those with genotype C. In contrast to G1896A, PreS deletion, T31C, T1753V, and A1762T/ G1764A were more frequent in subgenotype C2 than in subgenotype B2. A1762T/G1764A, T1753V, C1653T, and G1896A, except PreS deletion, consecutively increased with increasing age.Conclusion: HBV subgenotypes B2, C1, and C2 are endemic in Mainland China. HBV genotype C exhibits less replication activity in the young and harbors higher frequencies of the HCC-associated mutations than genotype B.Impact: These basic data could help evaluate the association of HBV variations with HCC. Cancer Epidemiol

Background Antibiotic-resistant Klebsiella pneumoniae are a major cause of hospital- and community-acquired infections, including sepsis, liver abscess, and pneumonia, driven mainly by the emergence of successful high-risk clonal lineages. The K. pneumoniae sequence type (ST) 307 lineage has appeared in several different parts of the world after first being described in Europe in 2008. From June to October 2019, we recorded an outbreak of an extensively drug-resistant ST307 lineage in four medical facilities in north-eastern Germany. Methods Here, we investigated these isolates and those from subsequent cases in the same facilities. We performed whole-genome sequencing to study phylogenetics, microevolution, and plasmid transmission, as well as phenotypic experiments including growth curves, hypermucoviscosity, siderophore secretion, biofilm formation, desiccation resilience, serum survival, and heavy metal resistance for an in-depth characterization of this outbreak clone. Results Phylogenetics suggest a homogenous phylogram with several sub-clades containing either isolates from only one patient or isolates originating from different patients, suggesting inter-patient transmission. We identified three large resistance plasmids, carrying either NDM-1, CTX-M-15, or OXA-48, which K. pneumoniae ST307 likely donated to other K. pneumoniae isolates of different STs and even other bacterial species (e.g., Enterobacter cloacae) within the clinical settings. Several chromosomally and plasmid-encoded, hypervirulence-associated virulence factors (e.g., yersiniabactin, metabolite transporter, aerobactin, and heavy metal resistance genes) were identified in addition. While growth, biofilm formation, desiccation resilience, serum survival, and heavy metal resistance were comparable to several control strains, results from siderophore secretion and hypermucoviscosity experiments revealed superiority of the ST307 clone, similar to an archetypical, hypervirulent K. pneumoniae strain (hvKP1). Conclusions The combination of extensive drug resistance and virulence, partly conferred through a “mosaic” plasmid carrying both antibiotic resistance and hypervirulence-associated features, demonstrates serious public health implications.