Genome-Wide Association Study Confirming Association of HLA-DP with Protection against Chronic Hepatitis B and Viral Clearance in Japanese and Korean

Hepatitis B virus (HBV) infection can lead to serious liver diseases, including liver cirrhosis (LC) and hepatocellular carcinoma (HCC); however, about 85–90% of infected individuals become inactive carriers with sustained biochemical remission and very low risk of LC or HCC. To identify host genetic factors contributing to HBV clearance, we conducted genome-wide association studies (GWAS) and replication analysis using samples from HBV carriers and spontaneously HBV-resolved Japanese and Korean individuals. Association analysis in the Japanese and Korean data identified the HLA-DPA1 and HLA-DPB1 genes with Pmeta = 1.89×10−12 for rs3077 and Pmeta = 9.69×10−10 for rs9277542. We also found that the HLA-DPA1 and HLA-DPB1 genes were significantly associated with protective effects against chronic hepatitis B (CHB) in Japanese, Korean and other Asian populations, including Chinese and Thai individuals (Pmeta = 4.40×10−19 for rs3077 and Pmeta = 1.28×10−15 for rs9277542). These results suggest that the associations between the HLA-DP locus and the protective effects against persistent HBV infection and with clearance of HBV were replicated widely in East Asian populations; however, there are no reports of GWAS in Caucasian or African populations. Based on the GWAS in this study, there were no significant SNPs associated with HCC development. To clarify the pathogenesis of CHB and the mechanisms of HBV clearance, further studies are necessary, including functional analyses of the HLA-DP molecule

Intravascular large B-cell lymphoma resembling invasive fungal rhinosinusitis: An autopsy case report

AbstractIntravascular large B-cell lymphoma (IVLBCL) is a rare subtype of malignant lymphoma (ML). Here, we present a case of IVLBCL initially suspected as invasive fungal rhinosinusitis (IFRS). A 64-year-old woman was referred to our hospital due to persistent fever, headache, and rhinorrhea. After admission, her overall condition rapidly deteriorated, leading to a diagnosis of septic shock. Blood examination revealed elevated serum lactate dehydrogenase and soluble interleukin 2 receptor levels suggestive of ML. Computed tomography revealed a high-density area with calcifications within the sinus cavity. Although IFRS was the primary suspicion, subsequent endoscopic sinus surgery disconfirmed this hypothesis based on histological findings. Unfortunately, the patient succumbed to multiple organ failure 12 days after admission, with an autopsy confirming IVLBCL. It is crucial to consider IVLBCL as a potential differential diagnosis in cases involving fever of unknown origin and progressive deterioration of the general condition

Genome-wide copy number variation analysis of hepatitis B infection in a Japanese population

Hepatitis B: Gene copy numbers associated with risk of infection The risk of contracting the hepatitis B virus may be linked to the number of copies of certain genes in an individual’s genome. A Japanese team led by Masataka Kikuchi, Osaka University, and Akihiro Nakaya, University of Tokyo, looked for repeated segments of the genome, known as copy number variants (CNVs), that differed between people with hepatitis B infections and those without. Studying around 3000 individuals of Japanese descent, the researchers identified several rare CNVs associated with immune function in hepatitis-affected individuals. They also found a common CNV in a gene called CNTN6 that the hepatitis B virus often uses to integrate itself into the genome of liver cells, a process that can lead to cancer. The findings underscore the importance of CNVs as inherited risk factors for hepatitis B and other viral infections

Gene therapy of c-myc suppressor FUSE-binding protein-interacting repressor by Sendai virus delivery prevents tracheal stenosis.

Acquired tracheal stenosis remains a challenging problem for otolaryngologists. The objective of this study was to determine whether the Sendai virus (SeV)-mediated c-myc suppressor, a far upstream element (FUSE)-binding protein (FBP)-interacting repressor (FIR), modulates wound healing of the airway mucosa, and whether it prevents tracheal stenosis in an animal model of induced mucosal injury. A fusion gene-deleted, non-transmissible SeV vector encoding FIR (FIR-SeV/ΔF) was prepared. Rats with scraped airway mucosae were administered FIR-SeV/ΔF through the tracheostoma. The pathological changes in the airway mucosa and in the tracheal lumen were assessed five days after scraping. Untreated animals showed hyperplasia of the airway epithelium and a thickened submucosal layer with extensive fibrosis, angiogenesis, and collagen deposition causing lumen stenosis. By contrast, the administration of FIR-SeV/ΔF decreased the degree of tracheal stenosis (P < 0.05) and improved the survival rate (P < 0.05). Immunohistochemical staining showed that c-Myc expression was downregulated in the tracheal basal cells of the FIR-SeV/ΔF-treated animals, suggesting that c-myc was suppressed by FIR-SeV/ΔF in the regenerating airway epithelium of the injured tracheal mucosa. The airway-targeted gene therapy of the c-myc suppressor FIR, using a recombinant SeV vector, prevented tracheal stenosis in a rat model of airway mucosal injury