Hepatitis: Japan

Ishibashi H, Komori A, Shimoda S, Gershwin ME. · Clinical Research Center, National Hospital Organization (NHO), Nagasaki Medical Center, and Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. · Semin Liver Dis. · Pubmed #17520519 No free full text.

Abstract: The principle of therapy for chronic inflammatory liver diseases is the removal of causal agents. For autoimmune liver diseases, however, total removal of causal agents and immune cells is impossible. Therefore, autoimmune liver diseases are presently treated by suppression of the immune response. Autoimmune hepatitis is characteristically responsive to corticosteroids, often used in combination with azathioprine to obtain a steroid-sparing effect. For primary biliary cirrhosis, ursodeoxycholic acid is safe and is the first choice for treatment. Treatment of this autoimmune liver disease should also address various symptoms and complications arising from any associated autoimmune diseases, particularly cholestasis and cirrhosis-related complications. For primary sclerosing cholangitis there are no established immunomodulatory therapies, but medical, endoscopic, and surgical treatments are applicable to this disease. Liver transplantation becomes indicated during the eventual end stages of each of these immune-mediated liver diseases.

Miyamura T. · National Institute of Infectious Diseases, 1-23-1 Toyama Shinjuku-ku, Tokyo 162-8640, Japan. · Adv Drug Deliv Rev. · Pubmed #17889399 No free full text.

This publication has no abstract.

Miyakawa Y, Yoshizawa H. · Miyakawa Memorial Research Foundation, Minami-Aoyama 2-19-8, Minato-Ku, Tokyo 107-0062, Japan. · Hepatol Res. · Pubmed #17092770 No free full text.

This publication has no abstract.

Tazuma S. · Department of General Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. · Hepatol Res. · Pubmed #17035081 No free full text.

This publication has no abstract.

Abe M, Akbar SM, Onji M. · Third Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan. · Hepatol Res. · Pubmed #16890177 No free full text.

This publication has no abstract.

Kurosaki M, Izumi N. · Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, 1-26-1 Kyonan-cho, Musashino-shi, Tokyo 180-8610, Japan. · Hepatol Res. · Pubmed #16303326 No free full text.

This publication has no abstract.

Nakamura H. · Division of Hepatobiliary and Pancreatic Medicine, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan. · Hepatol Res. · Pubmed #16290223 No free full text.

This publication has no abstract.

Kaito M. · Department of Gastroenterology and Hepatology, Institute of Clinical Medicine and Biomedical Sciences, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan. · Hepatol Res. · Pubmed #15967711 No free full text.

This publication has no abstract.

Yokosuka O. · Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ward, Chiba City, Chiba 260-8670, Japan. · Hepatol Res. · Pubmed #15869903 No free full text.

This publication has no abstract.

Yokosuka O. · Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ward, Chiba City, Chiba 260-8670, Japan. · Hepatol Res. · Pubmed #15862782 No free full text.

This publication has no abstract.

Kakumu S. · Gastroenterology Division, Department of Internal Medicine, Aichi Medical University School of Medicine, 21 Karimata, Yazako, Nagakute-cho, Aichi-gun, Aichi-ken 480-1195, Japan. · Hepatol Res. · Pubmed #15857808 No free full text.

This publication has no abstract.

Hirata Y, Sudoh M, Kohara M. · Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan. · Uirusu. · Pubmed #19374199 links to  free full text

Abstract: Hepatitis C virus (HCV) develops persistent infection in most infected patients, and eventually cause chronic hepatitis, liver cirrhosis and then hepatocellular carcinoma. The combination therapy of PEG-IFN and ribavirin improves the efficacy in many patients, while it does not lead to sufficient achievements in genotype1b patients. To invent new anti-HCV reagent, we focused on host factors which HCV take advantage of in its life-cycle. We identified serine palmitoyltransferase inhibitor as anti-HCV reagent through high-through put screenig using HCV replicon cells. Moreover, we evaluate the anti-HCV effect of SPT-inhibitor in vivo with humanized chimeric mice. SPT-inhibitor led to rapid decline in serum HCV-RNA of about 1-2log within 8 day, futhermore the combination therapy of SPT-inhibitor and PEG-IFN achieved about 3log reduction in serum HCV-RNA. At last, we investigated the mechanism of anti-HCV effect of SPT-inhibitor. It has been reported that sphingolipids and cholesterol compose the lipid raft, in which the replication of HCV occur. We investigated the influence of SPT-inhibitor to lipid rafts by analysing the detergent resistant membrane (DRM). The analysis proved that SPT inhibitor got HCV RNA dependent RNA polymerase (NS5B) to move to detergent soluble fraction from DRM, and Biacore analysis indicated the binding of sphingomyelin to NS5B. These results suggested SPT inhibitor got NS5B to release from replication complex.

Suzuki T, Masaki T, Aizaki H. · National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo. · Uirusu. · Pubmed #19374198 links to  free full text

Abstract: A robust system for production of recombinant infectious hepatitis C virus (HCV) has been established in 2005 and classical virological techniques are now able to be applied to the HCV research, especially regarding molecular mechanisms on virion assembly and maturation. We recently demonstrated that the C-terminal serine cluster of NS5A is a determinant of NS5A interaction with Core and the subcellular localization of NSSA. Mutation of this cluster blocks the NS5A-Core interaction, resulting in perturbation of association between Core and HCV RNA. It is thus tempting to consider that NS5A plays a key role in transporting the viral genome RNA synthesized by the replication complex to the surface of lipid droplets (LDs) or LD-associated membranes, where Core localizes, leading to facilitation of nucleocapsid formation. We also demonstrated an important role of cholesterol and sphingolipid in HCV infection and virion maturation. Specifically, mature HCV particles are rich in cholesterol. Depletion of cholesterol from HCV or hydrolysis of virion-associated sphingomyelin results in a loss of infectivity, and the addition of exogenous cholesterol restores infectivity. In addition, cholesterol and sphingolipid on the HCV membrane play a key role in virus internalization. Finally, inhibitors of the sphingolipid biosynthetic pathway efficiently block virion production.

Kato N. · Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences. · Uirusu. · Pubmed #19374197 links to  free full text

Abstract: The studies on the mechanism of HCV replication proliferated after the development of cell culture based-subgenomic HCV replicon system and genome-length HCV RNA replication system. Furthermore, these RNA replication systems have been improved to be suitable systems for the screening of anti-HCV reagents by the introduction of reporter genes such as luciferase. Genetic analysis of HCV RNAs obtained in long-term cell culture of HCV replicon or genome-length HCV RNA-harboring cells revealed that genetic mutations in HCV RNAs accumulated in a time-dependent manner. The genetic diversity of HCVs was also enlarged in a time-dependent manner. The appearance of adaptive mutation in HCV replicon or genome-length HCV RNA is one of characteristic features of HCV RNA replication system. Although human hepatoma-derived HuH-7 cell line was mainly used for HCV RNA replication systems, a specific combination of adaptive mutations led to develop the HCV RNA replication systems using a new human hepatoma cell line other than HuH-7.

Moriishi K, Mori Y, Matsuura Y. · Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, 3-1, Yamadaoka, Suita, Osaka 565-0871, Japan. · Uirusu. · Pubmed #19374196 links to  free full text

Abstract: Hepatitis C virus (HCV) is a major causative agent of blood-borne hepatitis. Most of the HCV-positive individuals have been chronically infected with the virus for decades, leading to development of steatosis, cirrhosis and ultimately hepatocellular carcinoma. In addition, cryoglobulinemia and type 2 diabetes mellitus are associated with a chronic infection with HCV. Hepatocellular carcinoma induced by HCV infection is not caused by only the repeated inflammations but also the biological activity of HCV proteins. HCV core protein has been reported as a component of the viral nucleocapsid as well as the pathogenic factor that could induce the production of oxidative stress and progression of cell growth. In this review, we summarize the current status of our knowledge regarding to the processing and pathogenicity of HCV core protein.

Ueno Y, Sollano JD, Farrell GC. · Tohoku University Graduate School of Medicine, Division of Gastroenterology, 1-1 Seiryo, Aobaku, Sendai 980-8574, Japan. · J Gastroenterol Hepatol. · Pubmed #19368633 No free full text.

Abstract: Chronic hepatitis C virus (HCV) infection accounts for most cases of hepatocellular carcinoma (HCC) in Japan and is the second major cause in many other countries. Development of HCC takes a considerable time after onset of HCV infection, between 20-40 years in most cases, and usually develops after cirrhosis is established. Although only a minority of HCV infections reach this stage, the high prevalence of chronic HCV infection in many countries (1-3%) is such that HCC related to HCV infection poses a significant public health issue 20-50 years after the onset of HCV epidemics. Due to advances in testing, and accessibility of clean, disposable medical apparatus including syringes and needles, and particularly screening of donor blood for anti-HCV and by nucleic acid testing, new cases of HCV infection have decreased in most countries, except for continued transmission by injection drug users (IDU). A key difference between HBV and HCV infection is that HCV can be eradicated by effective antiviral treatment. Sustained eradication of HCV reverses hepatic fibrosis, thereby preventing progression to cirrhosis and risk of HCC. Further, it has been well demonstrated that interferon-based antiviral therapy suppresses development of HCC in high-risk patients, particularly when sustained viral response (SVR) is obtained. In summary, the two key approaches to prevent development of HCV-related HCC are primary prevention of HCV infection (adequate programs to screen donor blood, universal precautions to stop medical transmission of blood-borne viruses, curbing transmission by IDU) and potent antiviral therapy of chronic HCV infection.

Saito M, Kohno K. · · Tanpakushitsu Kakusan Koso. · Pubmed #19348256 No free full text.

This publication has no abstract.

Saito T, Nishise Y, Ishii R, Watanabe H, Suzuki K, Kawata S. · Department of Gastroenterology, Yamagata University School of Medicine, Japan. · Nippon Shokakibyo Gakkai Zasshi. · Pubmed #19346718 No free full text.

This publication has no abstract.

Inoue K, Watanabe T, Yamada M, Yoshiba S. · Showa University Fujigaoka Hospital, Japan. · Nippon Shokakibyo Gakkai Zasshi. · Pubmed #19346717 No free full text.

This publication has no abstract.

Koike K. · Department of Infectious Diseases, University of Tokyo, Japan. · Nippon Shokakibyo Gakkai Zasshi. · Pubmed #19346715 No free full text.

This publication has no abstract.

Saiki I, Yamazaki M, Matsumoto K. · Division of Pathogenic Biochemistry, Institute of Natural medicine, University of Toyama, Japan. · Yakugaku Zasshi. · Pubmed #19336991 links to  free full text

Abstract: The Core University Program provides a framework for international cooperative research in specifically designated fields and topics, centering around a core university in Japan and its counterpart university in other countries. In this program, individual scientists in the affiliated countries carry out cooperative research projects with sharply focused topics and explicitly delineated goals under leadership of the core universities. The Core University Program which we introduce here has been renewed since 2001 under the support of both the Japan Society for the Promotion of Science (JSPS) and the National Research Council of Thailand (NRCT). Our program aims to conduct cooperative researches particularly focusing on Natural Medicine in the field of Pharmaceutical Sciences. Institute of Natural Medicine at University of Toyama (Japan), Faculty of Pharmaceutical Sciences at Chulalongkorn University (Thailand), and Chulabhorn Research Institute (Thailand) have been taking part in this JSPS-NRCT Core University Program as core universities. The Program is also supported by the 20 institution members in both countries. This program is running the five research subject under a key word of natural medicine which are related to i) age-related diseases, ii) allergy and cancer, iii) hepatitis and infectious diseases, iv) structure, synthesis, and bioactivity of natural medicines, and v) molecular biology of Thai medicinal plant components and database assembling of Thai medicinal plants. The program also encourages university members to strengthen related research activities, to share advanced academic and scientific knowledge on natural medicines.

Yamagiwa S, Kamimura H, Ichida T. · Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510, Japan. · Med Mol Morphol. · Pubmed #19294486 No free full text.

Abstract: The liver is a distinctive immune organ with predominant innate immunity, being rich in innate immune cells such as natural killer (NK) cells. In humans, NK cells comprise about 30%-50% of intrahepatic lymphocytes, whereas peripheral blood lymphocytes contain about 5%-20% NK cells. Accumulating evidence suggests that NK cells play an important role not only in host defense against invading microorganisms and tumor transformation in the liver but also in liver injury and repair. In recent years, significant progress has been made in terms of understanding how NK cells recognize their target cells and carry out their effector functions. It is now clear that NK cells are strictly regulated by numerous activating and inhibitory NK cell receptors that recognize various classes of cell surface ligands, some of which are expressed by normal healthy cells. Therefore, to further elucidate the involvement of NK cells in the pathogenesis of liver diseases, an understanding of recent advances in NK cell biology is crucial. This review provides an overview of recent advances in our knowledge of human NK cell receptors and their ligands in the context of liver diseases.

Morita S, Matsuda Y, Oshima T, Kubota T, Kawauchi Y, Kobayashi M, Nomoto M, Aoyagi Y. · The Third Department of Internal Medicine, Niigata University School of Medicine, Japan. · Nippon Shokakibyo Gakkai Zasshi. · Pubmed #19262054 No free full text.

Abstract: A 73-year-old man with chronic hepatitis C was Successfully treated for hepatocellular carcinoma (HCC) by localized treatment. During the follow-up period, abdominal computed tomography (CT) revealed no HCC recurrence in the liver. However, 9 months after the treatment, abdominal lymph nodes appeared enlarged on CT. Laparoscopic biopsy of the lymph nodes showed that the lesion was HCC, and TS-1/cisplatin chemotherapy was performed. However, extra-hepatic lymph nodes rapidly grew, leading to obstructive jaundice and finally death 10 months after of HCC metastasis. Although abdominal lymph node metastasis of HCC has been widely considered to be rare, the confirmation of effective therapy is awaited because histological studies have suggested that this pathologic lesion may occur more often than expected.

Kasuya T, Kuroda S. · Osaka University, Institute of Scientific and Industrial Research, Department of Structural Molecular Biology, Ibaraki, Japan. · Expert Opin Drug Deliv. · Pubmed #19236207 No free full text.

Abstract: A wide variety of nanoparticles (NPs) that can deliver incorporated therapeutic materials such as compounds, proteins, genes and siRNAs to the human liver have been developed to treat liver-related diseases. This review describes NP-based drug and gene delivery systems such as liposomes (including lipoplex), polymer micelles, polymers (including polyplex) and viral vectors. It focuses upon the modification of these NPs to enhance liver specificity or delivery efficiency in vitro and in vivo. We discuss recent advances in drug and gene delivery systems specific to the human liver utilizing bio-nanocapsules comprising hepatitis B virus (HBV) envelope L protein, which has a pivotal role in HBV infection. These NP-based medicines may offer novel strategies for the treatment of liver-related diseases and contribute to the development of nanomedicines targeting other tissues.

Kiuchi K, Kitagawa C, Miyashiro M. · Department of Ophthalmology, Osaka Saiseikai Izuo Hospital, Osaka, Japan. · Nippon Ganka Gakkai Zasshi. · Pubmed #19227928 No free full text.

Abstract: BACKGROUND: We treated a patient with anterior ischemic optic neuropathy caused by peginterferon. CASE: Upon medical examination of the eyes before starting interferon therapy for chronic hepatitis C at Saiseikai Izuo hospital, a 64-year-old man showed corrected visual acuity of 0.9 in the right eye and 1.0 in the left. No abnormality was visible in either eye except for mild cataracts. Six weeks after combination therapy with peginterferon alpha-2b and ribavirin was started, corrected visual acuity was found to have decreased in the right eye, and swelling of the optic nervehead in both eyes was evident. Bilateral anterior ischemic optic neuropathy caused by interferon therapy was diagnosed. Combination therapy with peginterferon alpha-2 b and ribavirin was discontinued, and administration of prednisolone was started at a dose of 60 mg. However, visual acuity declined in both eyes and the visual field defects worsend. At the most recent examination, visual acuity was 1.0 in the right eye and 0.01 in the left. The visual field included only the temporal periphery in the left eye, and part of the central and upper temporal periphery in the right. CONCLUSION: Since the outcome of visual acuity and visual fields in anterior ischemic optic neuropathy caused by interferon can be poor, an effective therapy for this complication needs to be developed.