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- 저자 : ( Tatsuya Kanto ) (검색결과 3 건)
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HCV Elimination in Japan: The Japanese Policy and Outcome
( Tatsuya Kanto ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1
In Japan, estimated number of chronic HBV infection was 1.1-1.4 million and that of chronic HCV was 1.9-2.3 million in 2000. The research on National Database (NDB) estimated number of chronic HBV infection on treatment was 0.16 million and that of chronic HCV was 0.47 million in 2015, respectively. The mortality of HCC had been increasing and hit the peak at around 2002, which subsequently started to decrease. Real-world clinical data have proven that direct anti-viral agents (DAAs) successfully eradicate HCV from more than 95% of the infected patients. In the clinical practice in Japan, optimization of DAAs treatment has been done based on HCV genotypes, stages of liver disease (chronic hepatitis or compensated/decompensated cirrhosis), prior experience of DAAs and the pattern of resistance-associated substitutions (RAS) on treatment. Of particular importance, meticulous care is needed for the treatment of patients with prior DAA failure and decompensated liver cirrhosis. Such tailored DAA treatment is guided by the Guidelines for the management of hepatitis C virus infection, updated and issued from Japan Society of Hepatology (JSH). Most of DAAs have been approved and registered in Japan, which enables us to choose multiple treatment options. In addition, for patients on treatment, drug prices of DAAs and examination expenses should be covered by special subsidy program for viral hepatitis. The national and local government cover the amount in excess of 100-200 USD of the cost of treatment. Japan has a national action plan for addressing viral hepatitis called, Basic Act on Hepatitis Measures, established in 2009. Basic Guidelines for Promotion of Control Measures for Hepatitis is issued in 2011 and was updated in 2016, comprising 9 principles in order to promote measures to prevent hepatitis B and C (Oza N, Kanto T et al., Hepatology Research, 2017). There are few countries like Japan that implement strategy against viral hepatitis targeting general population. According to these guidelines, national and local government share screening costs for testing hepatitis B and C for those who are over 40 years old residents. Thus, out-of-pocket expenses from examinees are free of charge or reduced to the minimum. From December 2018, special coverage program of medical expenses, shared by central and local government, has started for patients with HBV- or HCV-induced liver cancer and decompensated cirrhosis. However, in the cascade-of-care of viral hepatitis in Japan, significant gaps still remain in the diagnosis, treatment and their transition of patients in need. Questionnaire analysis for general people in Japan, which was performed in 2011 and 2017 by the government-funded research group including us, revealed that information regarding clinics and hospitals where testing is available for free has not been well disseminated. In addition, lack of correct knowledge on viral hepatitis in ordinally people sometimes induce stigma and discrimination against patients. Therefore, awareness raising in general people still in great demand for promoting hepatitis policy in Japan. The Hepatitis Information Center (HIC), established in the Research Center for hepatitis and Immunology, National Center for Global health and Medicine in 2008. The HIC has been collaborating with 71 regional core hospitals to promote hepatitis measures in Japan. According to the nationwide annual survey conducted by us, regional core centers have come to play varied roles in hepatitis treatment and expanded their programs, including awareness raising in general people, education of health care workers and hepatitis medical coordinators (HMC) (Setoyama H, Kanto T, et al., Hepatology Research, 2019). In order to achieve HCV elimination target by 2030, the strengthening of hepatitis care networks is needed that include regional core centers, specialized medical institutions, primary care physicians, HMCs and local governments. Several advantages have been prevailed in Japanese health care systems for patients with viral liver disease compared to those in countries in Asia and Pacific regions. Therefore, Japan should take a lead in helping the implementation of practical hepatitis action plan to each country where in need.
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( Kazumoto Murata ),( Masaya Sugiyama ),( Tatsuji Kimura ),( Sachiyo Yoshio ),( Tatsuya Kanto ),( Mai Asano ),( Yoshihiko Aoki ),( Tsutomu Takeda ),( Masaaki Korenaga ),( Masatoshi Imamura ),( Naohiko 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1
Background: Genetic variation of interleukin-28B (IL28B), encoding IFN-l3, predict non-responders to pegylated interferon-α/ ribavirin (Peg-IFN/RBV) therapy in chronic hepatitis C (CHC). However, it remains unknown whether IL28B is a functional phenotype, and why it failed to predict treatment responses at 20%. Methods: Message and protein levels of IFN-l3 induced by ex vivo stimulation of peripheral blood mononuclear cells (PBMC) with toll-like receptor agonists (TLR3; poly I: C, TLR7; R-837) were measured by quantitative real-time PCR and our newly developed chemiluminescence enzyme immunoassays, and compared with the clinical data. BDCA-3 or -4+dendritic cells (DC) was negatively or positively selected by Magnet-Associated Cell Sorting. Results: We firstly found that BDCA-4+DCs were the main producers of IFN-ls when stimulated with R-837 whereas BDCA-3+DCs were main producers of IFN-ls when stimulated with poly I: C, using PBMC from healthy volunteers. We also found that detectable levels of IFN-ls were inducible using small amount of PBMC by R-837, not poly I: C. When stimulated with R-837, IFN-l3 was more robustly up-regulated in the PBMC from CHC patients with favorable genotype (TT in rs8099917, n = 59) for the response to Peg-IFN/RBV than non-TT (n = 41) whereas no differences was observed in IFN-l1 or IFNl2, which may support our GWAS data. Importantly, protein levels of IFN-l3 induced by R-837 clearly differentiated the response to Peg-IFN/RBV treatment (p = 1.0×10-10), including discrepant cases such as VR in patients with TG/GG or NVR in TT genotype. Our method more accurately predicted treatment efficacies (95.7%) than IL28B genotyping (65.2%) did. Conclusions: Genetic variations in IL28B basically affect IFNl3 production, but different amount of IFN-l3 production determines the outcomes of Peg-IFN/RBV treatment. This study, for the first time, presents compelling evidence that genetic variations in IL28B confer a functional phenotype. Our method may provide more accurate prediction for the efficacy of Peg-IFN/RBV.
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