Objective To examine recent trends of acute infection with hepatitis B virus (HBV) in Japan by nationwide surveillance and phylogenetic analyses. Methods During 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. Results HBV 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 1991e1996, 29.3% during 1997e2002, and 50.0% during 2003e2008 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. Conclusions Acute 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.Hepatitis B virus (HBV) has been classified into 10 genotypes, designated AeJ, based on a >8% divergence in the full-genome sequence. Significance of this studyWhat is already known about this subject?< In Japan, a national prevention programme was started in 1986 with selective vaccination of babies born to mothers who carry hepatitis B virus (HBV). Since then, the prevalence of hepatitis B surface antigen among younger generations has decreased sharply. < However, retrospective studies indicate that the frequency of HBV genotype A is increasing among patients with acute hepatitis B (AHB) within the capital region of Japan. < Infection with genotype A more often persists than infection with other genotypes. < Because there is no reliable and comprehensive surveillance system for AHB in Japan, the incidence of AHB and factors responsible for changes over many years are not known. What are the new findings?< This is a prospective cohort study for surveillance of AHB throughout Japan in a national research programme. < The incidence of AHB in Japan has not decreased, because genotype A infections have increased over time. < Genotype A infections started to increase in the capital region of Japan, and then spread to other r...
Bile-duct injury observed in hepatic graft versus host disease (GVHD) is regarded as an immune-mediated injury, although its precise mechanism is unclear. However, recent studies have suggested the involvement of Fas-mediated cell death in this immune-mediated cholangiopathy. In this study, we first showed the constitutive expression of Fas receptor by cholangiocytes in situ from normal BALB/c mice, which was upregulated in GVHD mice. Also, we confirmed the Fas protein expression in the isolated cholangiocytes from normal BALB/c mice by immunocytochemistry and immunoblotting. Furthermore, the addition of Bile-duct injury or cholangiopathy is observed in hepatic graft versus host disease (GVHD). 1 Nondestructive or destructive cholangitis with degeneration of bile-duct epithelium, as seen in primary biliary cirrhosis (PBC), is a hallmark of acute GVHD. 2 These immune-mediated cholangiopathies eventually develop hepatic failure. Indeed, chronic allograft rejection, another form of immune-mediated cholangitis, is one of the leading causes of hepatic allograft loss. However, the precise mechanism of cholangiocyte injury is unknown. Subsequently, animal models of GVHD have been developed to study the mechanism of cholangiopathies. Those murine models of GVHD showed the minor histocompatibility antigen is believed to be the main target, and the nature of inflammation, mainly CD4-positive or CD8-positive lymphocytes, were well documented. 3 However, the cellular mechanism of cholangiopathy occurring in GVHD is still unclear. Recently, apoptosis is found to be involved in several inflammatory processes. 4,5 The Fas, a 45-kd type I cell-surface receptor, is a member of tumor necrosis factor (TNF) receptor superfamily. 6 Stimulation of Fas receptor with its ligand, FasL, leads to apoptosis. 7,8 In mice, the administration of agonistic Fas antibody leads to fulminant hepatic failure in the recipients. 9 In liver diseases related to hepatitis virus infection, Fas is identified on hepatocytes, suggesting that cell death of hepatocytes occurs through Fas/FasL interaction. 10 Fas antigen expressions by cholangiocytes were reported previously in humans 11 and rats, 12 and enhanced expression of Fas antigen on cholangiocytes was also reported in PBC. 13 However, the states of Fas expression in normal cholangiocytes in mice and the role of Fas/FasL system in immune-mediated cholangiopathies remain unknown. In this study, we investigated the Fas receptor expression by cholangiocytes and its role in cholangiopathy in murine GVHD model. Furthermore, we show the efficacy of the blocking of Fas/FasL system using both in vitro and in vivo, which might give novel therapeutic strategies to progressive human hepatobiliary diseases. MATERIALS AND METHODS AnimalsBALB/c CrSlc mice (H-2 d , MLS 3a ), B10.D2 nSn mice (H-2 d , MLS 3b ), and MRL/Mp J (lpr/lpr) mice, all of which were female and 6 weeks of age, were purchased from Japan SLC (Hamamatsu, Japan) and fed ad libitium under a standard animal-care manual
In these three cases with active ulcerative colitis during pregnancy, granulocytapheresis as a non-pharmacologic treatment was effective and safe. In case 3 that did not respond well to the initial granulocytapheresis sessions, a moderate dose of prednisolone enhanced the efficacy of granulocytapheresis and tapering of prednisolone shortly after administration was not associated with relapse.
Primary biliary cholangitis (PBC) is a chronic and cholestatic autoimmune liver disease caused by the destruction of intrahepatic small bile ducts. Our previous genome-wide association study (GWAS) identified six susceptibility loci for PBC. Here, in order to further elucidate the genetic architecture of PBC, a GWAS was performed on an additional independent sample set, then a genome-wide meta-analysis with our previous GWAS was performed based on a whole-genome single nucleotide polymorphism (SNP) imputation analysis of a total of 4,045 Japanese individuals (2,060 cases and 1,985 healthy controls). A susceptibility locus on chromosome 3q13.33 (including ARHGAP31, TMEM39A, POGLUT1, TIMMDC1, and CD80) was previously identified both in the European and Chinese populations and was replicated in the Japanese population (OR = 0.7241, P = 3.5 × 10−9). Subsequent in silico and in vitro functional analyses identified rs2293370, previously reported as the top-hit SNP in this locus in the European population, as the primary functional SNP. Moreover, e-QTL analysis indicated that the effector gene of rs2293370 was Protein O-Glucosyltransferase 1 (POGLUT1) (P = 3.4 × 10−8). This is the first study to demonstrate that POGLUT1 and not CD80 is the effector gene regulated by the primary functional SNP rs2293370, and that increased expression of POGLUT1 might be involved in the pathogenesis of PBC.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.