Hepatitis B virus strains of subgenotype A2 with an identical sequence spreading rapidly from the capital region to all over Japan in patients with acute hepatitis B

ObjectiveTo examine recent trends of acute infection with hepatitis B virus (HBV) in Japan by nationwide surveillance and phylogenetic analyses.MethodsDuring 1991 through 2009, a sentinel surveillance was conducted in 28 national hospitals in a prospective cohort study. Genotypes of HBV were determined in 547 patients with acute hepatitis B. Nucleotide sequences in the preS1/S2/S gene of genotype A and B isolates were determined for phylogenetic analyses.ResultsHBV genotype A was detected in 137 (25% (accompanied by genotype G in one)) patients, B in 48 (9%), C in 359 (66%), and other genotypes in the remaining three (0.5%). HBV persisted in five with genotype A including the one accompanied by genotype G; another was co-infected with HIV type 1. The genotype was A in 4.8% of patients during 1991-1996, 29.3% during 1997-2002, and 50.0% during 2003-2008 in the capital region, as against 6.5%, 8.5% and 33.1%, respectively, in other regions. Of the 114 genotype A isolates, 13 (11.4%) were subgenotype A1, and 101 (88.6%) were A2, whereas of the 43 genotype B isolates, 10 (23.3%) were subgenotype B1, 28 (65.1%) were B2, two (4.7%) were B3, and three (7.0%) were B4. Sequences of 65 (64%) isolates of A2 were identical, as were three (23%) of A1, and five (18%) of B2, but none of the B1, B3 and B4 isolates shared a sequence.ConclusionsAcute infection with HBV of genotype A, subgenotype A2 in particular, appear to be increasing, mainly through sexual contact, and spreading from the capital region to other regions in Japan nationwide. Infection persisted in 4% of the patients with genotype A, and HBV strains with an identical sequence prevailed in subgenotype A2 infections. This study indicates the need for universal vaccination of young people to prevent increases in HBV infection in Japan

Genetic and Histopathological Heterogeneity of Neuroblastoma and Precision Therapeutic Approaches for Extremely Unfavorable Histology Subgroups

Peripheral neuroblastic tumors (neuroblastoma, ganglioneuroblastoma and ganglioneuroma) are heterogeneous and their diverse and wide range of clinical behaviors (spontaneous regression, tumor maturation and aggressive progression) are closely associated with genetic/molecular properties of the individual tumors. The International Neuroblastoma Pathology Classification, a biologically relevant and prognostically significant morphology classification distinguishing the favorable histology (FH) and unfavorable histology (UH) groups in this disease, predicts survival probabilities of the patients with the highest hazard ratio. The recent advance of neuroblastoma research with precision medicine approaches demonstrates that tumors in the UH group are also heterogeneous and four distinct subgroups—MYC, TERT, ALT and null—are identified. Among them, the first three subgroups are collectively named extremely unfavorable histology (EUH) tumors because of their highly aggressive clinical behavior. As indicated by their names, these EUH tumors are individually defined by their potential targets detected molecularly and immunohistochemically, such as MYC-family protein overexpression, TERT overexpression and ATRX (or DAXX) loss. In the latter half on this paper, the current status of therapeutic targeting of these EUH tumors is discussed for the future development of effective treatments of the patients