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Regulation of microRNA by hepatitis B virus infection and their possible association with control of innate immunity

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World Journal of Gastroenterology 2014年第23期20卷 7197-7206页

作者： Xia Jiang Tatsuo Kanda Shuang Wu masato nakamura Tatsuo Miyamura Shingo Nakamoto Arup Banerjee Osamu Yokosuka Department of Gastroenterology and Nephrology Graduate School of MedicineChiba UniversityChiba 260-8677Japan Department of Molecular Virology Graduate School of MedicineChiba UniversityChiba 260-8677Japan Vaccine and Infectious Disease Research Center and Translational Health Science and Technology Institute Gurgaon-122016HaryanaIndia

Hepatitis B virus(HBV)chronically infects more than350 million people *** causes acute and chronic hepatitis,and is one of the major causes of cirrhosis and hepatocellular *** exist complex interactions between HBV and the immune system including adaptive and innate *** receptors(TLRs)and TLR-signaling pathways are important parts of the innate immune response in HBV *** is well known that TLR-ligands could suppress HBV replication and that TLRs play important roles in anti-viral *** immunological studies demonstrated that HBV e antigen(HBeAg)is more efficient at eliciting T-cell tolerance,including production of specific cytokines IL-2 and interferon gamma,than HBV core *** downregulates cytokine production in hepatocytes by the inhibition of MAPK or NF-κB activation through the interaction with receptor-interacting serine/threonine protein ***(miRNAs)are also able to regulate various biological processes such as the innate immune *** the expressions of approximately 1000 miRNAs were compared between human hepatoma cells HepG2 and HepG2.2.15,which could produce HBV virion that infects chimpanzees,using real-time RT-PCR,we observed several different expression levels in miRNAs related to *** we and others have shown that HBV modulates the host immune response,several of the miRNAs seem to be involved in the TLR signaling *** possibility that alteration of these miRNAs during HBV infection might play a critical role in innate immunity against HBV infection should be *** article is intended to comprehensively review the association between HBV and innate immunity,and to discuss the role of miRNAs in the innate immune response to HBV infection.

关键词： Hepatitis B virus HepG2.2.15 Innate immunity MicroRNA Persistent infection Toll-like receptor

Direct-acting Antiviral Agents for the Treatment of Chronic Hepatitis C Virus Infection

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Journal of Clinical and Translational Hepatology 2014年第1期2卷 1-6页

作者： Tatsuo Kanda Shingo Nakamoto masato nakamura Xia Jiang Tatsuo Miyamura Shuang wu Osamu Yokosuka Department of Gastroenterology and Nephrology Chiba University Graduate School of Medicine Inohana Chuo-ku Chiba Japan

Hepatitis C virus (HCV) is a leading cause of cirrhosis and hepatocellular carcinoma (HCC) in the US and ***,eradication of HCV may reduce the occurrence of HCC in HCV-infected *** 2011,the use of firstgeneration HCV NS3/4A protease inhibitors such as telaprevir and boceprevir was initiated for clinical treatment of *** of telaprevir and boceprevir plus peginterferon and ribavirin increased rates of sustained virological response (SVR) in HCV genotype 1-infected ***,this treatment regimen also led to severe adverse ***-generation direct-acting antiviral agents (DAAs) for HCV,such as simeprevir plus peg-interferon and ribavirin also resulted in higher SVR rates,with similar adverse events to other peg-interferon and ribavirin *** SVR rates in HCV genotype 1-and 2-infected patients were achieved with 12-16 weeks of sofosbuvir plus other class DAAs with/without ribavirin and 12 weeks of sofosbuvir plus ribavirin,respectively,For "difficult-to-treat"HCV-infected patients,more therapeutic options are *** studies examining the efficacy and adverse effects of such therapies will be required for the development of additional treatments.

关键词： Daclatasvir Interferon-free Protease inhibitors Simeprevir Sofosbuvir

Direct-acting Antivirals and Host-targeting Agents against the Hepatitis A Virus

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Journal of Clinical and Translational Hepatology 2015年第3期3卷 205-210页

作者： Tatsuo Kanda Shingo Nakamoto Shuang Wu masato nakamura Xia Jiang Yuki Haga Reina Sasaki Osamu Yokosuka Department of Gastroenterology and Nephrology Chiba University Graduate School of Medicine Inohana Chuo-ku Chiba Japan

Hepatitis A virus (HAV) infection is a major cause of acute hepatitis and occasionally leads to acute liver failure in both developing and developed *** effective vaccines for HAV are available,the development of new antivirals against HAV may be important for the control of HAV infection in developed countries where no universal vaccination program against HAV exists,such as *** are two forms of antiviral agents against HAV:direct-acting antivirals (DAAs) and host-targeting agents (HTAs).Studies using small interfering ribonucleic acid (siRNA) have suggested that the HAV internal ribosomal entry site (IRES) is an attractive target for the control of HAV replication and *** the HTAs,amantadine and interferon-lambda 1 (IL-29) inhibit HAV IRES-mediated translation and HAV *** kinase (JAK) inhibitors inhibit La protein expression,HAV IRES activity,and HAV *** on this review,both DAAs and HTAs may be needed to control effectively HAV infection,and their use should continue to be explored.

关键词： Amantadine DAA HAV HTA La protein Drug overview

Endoscopic papillary large balloon dilation for bile duct stones in elderly patients

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World Journal of Clinical Cases 2015年第4期3卷 353-359页

作者： Yuji Sakai Toshio Tsuyuguchi Harutoshi Sugiyama Reina Sasaki Dai Sakamoto masato nakamura Yuuto Watanabe Takao Nishikawa Shin Yasui Rintaro Mikata Osamu Yokosuka Department of Gastroenterology and Nephrology Graduate School of Medicine Chiba University

AIM: To investigate whether endoscopic papillary large balloon dilation(EPLBD) can be safety and effectively performed in patients aged ≥ 80 years. METHODS: Lithotomy by EPLBD was conducted in 106 patients with bile duct stones ≥ 13 mm in size or with three or more bile duct stones ≥ 10 mm. The patients were divided into group A(< 80 years) and group B(≥ 80 years). Procedure success rate, number of endoscopic retrograde cholangiopancreatographies(ERCP), and incidence of complications were examined in both ***: Group B tended to include significantly more patients with peripapillary diverticulum, hypertension, hyperlipemia, cerebrovascular disease/dementia, respiratory disease/cardiac disease, and patients administered an anticoagulant or antiplatelet agent(P < 0.05). The success rate of the initial lithotomy was 88.7(94/106)%. The final lithotomy rate was 100(106/106)%. Complications due to treatment procedure occurred in 4.72(5/106)% of the patients. There was no significant difference in procedure success rate, number of ERCP, or incidence of complications between group A and group ***: EPLBD can be safely performed in elderly patients, the same as in younger patients.

关键词： Elderly patients Endoscopic papillary large balloon dilation Endoscopic sphincterotomy Large bile duct stones Choledocholithiasis

New tapered metallic stent for unresectable malignant hilar bile duct obstruction

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World Journal of Clinical Cases 2015年第10期3卷 887-893页

作者： Yuji Sakai Toshio Tsuyuguchi Takao Nishikawa Harutoshi Sugiyama Reina Sasaki Dai Sakamoto Yuto Watanabe masato nakamura Shin Yasui Rintaro Mikata Osamu Yokosuka Department of Gastroenterology and Nephrology Graduate School of Medicine Chiba University

AIM: To examine the usefulness of a new tapered metallic stent(MS) in patients with unresectable malignant hilar bile duct ***: This new tapered MS was placed in 11 patients with Bismuth Ⅱ or severer unresectable malignant hilar bile duct obstruction, as a prospective study. The subjects were six patients with bile duct carcinoma, three with gallbladder cancer, and two with metastatic bile duct obstruction. Stenosis morphology was Bismuth Ⅱ: 7, Ⅲa: 3, and Ⅳ: 1. UMIN Clinical Trial Registry(UMIN000004758).RESULTS: MS placement was 100%(11/11) successful. There were no procedural accidents. The mean patency period was 208.401 d, the median survival period was 142.000 d, and the mean survival period was 193.273 d. Occlusion rate was 36.4%(4/11); the causes of occlusion were ingrowth and overgrowth in 2 patients each, 18.2%, respectively. Patients with occlusion underwent endoscopic treatment one more time and all were treatable. CONCLUSION: The tapered MS proved useful in patients with unresectable malignant hilar bile duct obstruction because it provided a long patency period, enabled re-treatment by re-intervention, and no procedural accidents occurred.

关键词： Malignant hilar bile duct obstruction Metallic stent Tapered metallic stent

IL-28B polymorphisms and treatment response in hepatitis C virus patients with persistently normal alanine aminotransferase

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World Journal of Hepatology 2013年第11期5卷 635-641页

作者： Tatsuo Miyamura Tatsuo Kanda masato nakamura Xia Jiang Shuang Wu Shingo Nakamoto Shigeru Mikami Nobuo Takada Fumio Imazeki Osamu Yokosuka Department of Gastroenterology and Nephrology Chiba University Graduate School of Medicine Department of Internal Medicine Kikkoman General Hospital Department of Internal Medicine Toho University Sakura Medical Centre Safety and Health Organization Chiba University

AIM:To examine the association between the interleukin 28B(IL-28B)genotype and treatment response in hepatitis C virus(HCV)-infected patients with persistently normal alanine aminotransferase(PNALT).METHODS:We compared the treatment response of HCV-infected patients with PNALT to that of patients with *** February 2010 and April2013,278 patients infected with HCV were enrolled in this *** of the patients were treated with peginterferon-alpha 2a or 2b plus *** addition,180μg of peginterferon alpha-2a or 1.5μg/kg peginterferon alpha-2b per week plus weight-based ribavirin(600-1000 mg/d)were typically administered for 24 wk to HCV genotype 2-infected patients or for 48-72 wk to HCV genotype 1-infected *** all of the patients,the IL-28B rs8099917 genotype was determined using a TaqMan single-nucleotide polymorphism *** RNA was measured using the COBAS TaqMan HCV ***:Female patients were dominant in the PNALT group(P<0.0001).Among 72 HCV genotype 1-infected patients with PNALT,the early virologic response(EVR)rates(P<0.01)and the sustained virologic response(SVR)rates(P<0.01)were higher in patients with the IL-28B TT genotype than in those with the IL-28B TG/GG *** HCV genotype 1-infected patients with PNALT,multivariate logistic-regression analysis showed that SVR was independently predicted by the IL-28B rs8099917 TT type(P<0.05)and having an EVR(P<0.01).The IL-28B rs8099917 TT genotype strongly correlated with treatment response in HCV genotype 1-infected Asian patients with ***:The IL-28B genotype may be useful for selecting HCV genotype 1-infected patients with PNALT who should receive interferon-based treatment.

关键词： Hepatitis C virus Interleukin 28B Persistent normal alanine aminotransferase levels Standard of care Treatment response

Sofosbuvir treatment and hepatitis C virus infection

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World Journal of Hepatology 2016年第3期8卷 183-190页

作者： masato nakamura Tatsuo Kanda Yuki Haga Reina Sasaki Shuang Wu Shingo Nakamoto Shin Yasui Makoto Arai Fumio Imazeki Osamu Yokosuka Department of Gastroenterology and Nephrology Chiba UniversityGraduate School of MedicineChiba 260-8670Japan Department of Molecular Virology Chiba UniversityGraduate School of MedicineChiba 260-8677Japan Safety and Health Organization Chiba UniversityChiba 263-8522Japan

Hepatitis C virus(HCV) infection is a serious problem *** use of interferon-based therapy has made HCV eradication *** recent appearance of direct-acting antiviral agents(DAAs) has changed HCV *** the use of DAAs with peginterferon and ribavirin has improved treatment ***,the combination of different orally administered DAAs has enabled interferon-free therapy with much higher efficacy and *** particular,sofosbuvir,a nucleotide-based NS5 B inhibitor,prevents HCV RNA synthesis by acting as a "chain terminator".Treatment with sofosbuvir has attained an extremely high rate of sustained virologic *** current review summarizes the efficacy and safety of sofosbuvir therapy.

关键词： Hepatitis C virus Interferon Interferonfree Genotype Sofosbuvir

Prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis by pancreatic duct stenting using a loop-tipped guidewire

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World Journal of Clinical Cases 2016年第8期4卷 213-218页

作者： Yuji Sakai Toshio Tsuyuguchi Harutoshi Sugiyama Masahiro Hayashi Jun-ichi Senoo Reina Sasaki Yuko Kusakabe masato nakamura Shin Yasui Rintaro Mikata Masaru Miyazaki Osamu Yokosuka Department of Gastroenterology and Nephrology Graduate School of Medicine Chiba University Department of General Surgery Graduate School of Medicine Chiba University

AIM: To examine whether it is possible to prevent the occurrence of post-endoscopic retrograde cholangiopancreatography(ERCP) pancreatitis in patients experiencing difficulties with selective biliary duct cannulation by pancreatic duct stenting using a looptipped ***: Procedure success rate, frequency of unintended insertion of the guidewire into side branches of the pancreatic duct, and incidence of procedural accidents were examined using a loop-tipped guidewire(Group A, 20 patients), and a conventional straighttype guidewire(Group B, 20 patients).RESULTS: The success rate of the procedure was 100% in both groups. Unintended insertion of the guidewire into a side branch of the pancreatic duct occurred 0.056 ± 0.23(0-1) times in Group A and 2.3 ±1.84(0-5) times in Group B; thus, unintended insertion of the guidewire into a side branch of the pancreatic duct was seen significantly less frequently in Group A. There were no procedural accidents in Group A, whereas pancreatitis occurred in one Group B patient; however, the difference between the two groups was not statistically significant. The serum amylase level after ERCP was 257.15 ± 136.4(88-628) IU/L in Group A, and 552.05 ± 534.57(101-2389) IU/L in Group B, showing a significantly lower value in Group A. Hyperamylasemia was found in two patients(10%) in Group A, and nine(45%) in Group B, showing a significantly lower value in Group ***: The results suggest that in patients who experience difficulties with biliary cannulation, the use of a loop-tipped guidewire for pancreatic duct stenting may assist with the prevention of post-ERCP pancreatitis, and thereby to a reduction of the risk of post-ERCP pancreatitis or hyperamylasemia.

关键词： Hyperamylasemia Post-endoscopic retrograde cholangiopancreatography pancreatitis Guidewire

Endoscopic papillary large balloon dilation for removal of bile duct stones

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World Journal of Gastroenterology 2014年第45期20卷 17148-17154页

作者： Yuji Sakai Toshio Tsuyuguchi Yoshiaki Kawaguchi Nobuto Hirata So Nakaji Katsuya Kitamura Shigeru Mikami Tatsuya Fujimoto Masashi Ijima Eishin Kurihara Shuhei Oana Takayoshi Nishino Ryo Tamura Dai Sakamoto masato nakamura Takao Nishikawa Harutoshi Sugiyama Hitoshi Yoshida Tetsuya Mine Osamu Yokosuka Department of Gastroenterology and Nephrology Graduate School of Medicine Chiba University Department of Gastroenterology Tokai University Hospital Department of Gastroenterology Kameda Medical Center Division of Gastroenterology Department of Medicine Showa University School of Medicine Department of Internal Medicine Kikkoman General Hospital Department of Gastroenterology Kimitsu Central Hospital Department of Gastroenterology Isesaki Municipal Hospital Department of Gastroenterology Iwate Medical University Hospital Department of Gastroenterology Tokyo Women’s Medical University Yachiyo Medical Center

AIM: To investigate the efficacy and outcomes of endoscopic papillary large balloon dilation (EPLBD) for bile duct stones in a multicenter prospective study.

关键词： Endoscopic retrograde cholangiopancreatography Endoscopic sphincterotomy Endoscopic papillary large balloon dilation Large bile duct stones Multiple bile duct stones