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Quantitation of HBsAg predicts response to entecavir therapy in HBV genotype C patients

World Journal of Gastroenterology 2012年第39期18卷 5570-5575页

作者： Etsuro Orito kei fujiwara Hiroshi Kanie Tesshin Ban Tomonori Yamada Katsumi Hayashi Department of Gastroenterology Nagoya Daini Red Cross HospitalNagoya 466-8650Japan

AIM： To analysis the factors that predict the response to entecavir therapy in chronic hepatitis patients with hepatitis B virus （HBV） genotype C. METHODS： Fifty patients [hepatitis B e antigen （HBeAg）- negative：HBeAg-positive = 26：24] with HBV genotype C, who received nalve entecavir therapy for 〉 2 years, were analyzed. Patients who showed HBV DNA levels ≥ 3.0 log viral copies/mL after 2 years of entecavir ther- apy were designated as slow-responders, while those that showed 〈 3.0 log copies/mL were termed rapid- responders. Quantitative hepatitis B surface antigen （HBsAg） levels （qHBsAg） were determined by the Archi- tect HBsAg QT immunoassay. Hepatitis B core-related antigen was detected by enzyme immunoassay. Pre-C and Core promoter mutations were determined using by polymerase chain reaction （PCR）. Drug-resistance muta- tions were detected by the PCR-Invader method. RESULTS： At year 2, HBV DNA levels in all patients in the HBeAg-negative group were 〈 3.0 log copies/mL. In contrast, in the HBeAg-positive group, 41.7% were slow-responders, while 58.3% were rapid-responders. No entecavir-resistant mutants were detected in the slow-responders. When the pretreatment factors were compared between the slow- and rapid-responders; the median qHBsAg in the slow-responders was 4.57 log IU/mL, compared with 3.63 log IU/mL in the rapid- responders （P 〈 0.01）. When the pretreatment factors predictive of HBV DNA-negative status at year 2 in all 50 patients were analyzed, HBeAg-negative status, low HBV DNA levels, and low qHBsAg levels were signifi- cant （P 〈 0.01）. Multivariate analysis revealed that the low qHBsAg level was the most significant predictive factor （P = 0.03）. CONCLUSION： Quantitation of HBsAg could be a use- ful indicator to predict response to entecavir therapy.

关键词： Chronic hepatitis B Quantitation of hepa-titis B surface antigen Entecavir Hepatitis B virusgenotype C SIow-responders Hepatitis B core-relatedantigen Core promoter mutation Pre-C mutation

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Genotype and phylogenetic characterization of hepatitis B virus among multi-ethnic cohort in Hawaii

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World Journal of Gastroenterology 2004年第15期10卷 2218-2222页

作者： Mayumi Sakurai Fuminaka Sugauchi Naoky Tsai Seiji Suzuki Izumi Hasegawa kei fujiwara Etsuro Orito Ryuzo Ueda Masashi Mizokami Department of Clinical Molecular Informative Medicine Nagoya City University Graduate School of Medical SciencesNagoya 467-8601Japan Division of Gastroenterology John A.Bums School of MedicineUniversity of HawaiiUSA Department of Clinical Internal Medicine and Molecular Science Nagoya City University Graduate School of Medical SciencesNagoya 467-8601Japan

AIM: Hepatitis B virus (HBV) genomes in carriers from Hawaii have not been evaluated previously. The aim of thepresent study was to evaluate the distribution of HBV genotypes and their clinical relevance in ***: Genotyping of HBV among 61 multi-ethnicc arriers in Hawaii was performed by genetic *** complete genomes and 61 core promoter/precore regions of HBV were sequenced ***: HBV genotype distribution among the 61 carderswas 23.0% for genotype A, 14.7% for genotype B and 62.3% for genotype C. Genotypes A, B and C were obtained from the carriers whose ethnicities were Filipino and Caucasian,Southeast Asian, and various Asian and Micronesian,respectively. All cases of genotype B were composed of recombinant strains with genotype C in the precore plus core region named genotype Ba. HBeAg was detected more frequently in genotype C than in genotype B (68.4% vs 33.3%, P<0.05) and basal core promoter (BCP) mutation (T1762/A1764) was more frequently found in genotype C than in genotype B. Twelve of the 38 genotype C strains possessed C at nucleotide (nt) position 1858 (C-1858).However there was no significant difference in clinical characteristics between C-1858 and T-1858 variants. Based on complete genome sequences, phylogenetic analysis revealed one patient of Micronesian ethnicity as having C1858 clustered with two isolates from Polynesia with *** addition, two strains from Asian ethnidties were clustered with known isolates in carriers from Southeast ***: Genotypes A, B and C are predominant types among multi-ethnic HBV carriers in Hawaii, and distribution of HBV genotypes is dependent on the ethnic background of the carriers in Hawaii.

关键词：基因型系统描述乙型肝炎病毒多种部队夏威夷 HBV 重组细胞

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Classifying genotype F of hepatitis B virus into F1 and F2 subtypes

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World Journal of Gastroenterology 2005年第40期11卷 6295-6304页

作者： Hideaki Kato kei fujiwara Robert G. Gish Hiroshi Sakugawa Hiroshi Yoshizawa Fuminaka Sugauchi Etsuro Orito Ryuzo Ueda Yasuhito Tanaka Takanobu Kato Yuzo Miyakawa Masashi Mizokami Department of Internal Medicine and Molecular Science Hepatology and Gastroenterology First Department of Medicine Department of Epidemiology and Control of Infectious Diseases Department of Clinical Molecular Informative Medicine Miyakawa Memorial Research Foundation

AIM： To explore the propriety of providing hepatitis B virus （HBV） genotypes F and H with two distinct genotypes. METHODS： Eleven HBV isolates of genotype F （HBV/F） were recovered from patients living in San Francisco, Japan, Panama, and Venezuela, and their full-length sequences were determined. Phylogenetic analysis was carded out among them along with HBV isolates previously reported. RESULTS： Seven of them clustered with reported HBV/F Isolates in the phylogenetic tree constructed on the entire genomic sequence. The remaining four flocked on another branch along with three HBV isolates formerly reported as genotype H. These seven HBV isolates, including the four in this study and the three reported, had a sequence divergence of 7.3-9.5% from the other HBV/F isolates, and differed by 〉13.7% from HBV isolates of the other six genotypes （A-E and G）. Based on a marked genomic divergence, falling just short of 〉8% separating the seven genotypes, these seven HBV/F isolates were classified into F2 subtype and the former seven into F1 subtype provisionally. In a pairwise comparison of the S-gene sequences among the 7 HBV/F2 isolates and against 47 HBV/F1 isolates as well as 136 representing the other six genotypes （A-E and G）, two clusters separated by distinct genetic distances ***： Based on these analyses, dassifying HBV/ F isolates into two subtypes （F1 and F2） would be more appropriate than providing them with two distinct genotypes （F and H）.

关键词： Genotypes Hepatitis B virus Phylogeneticanalysis Subtypes

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New combination test for hepatitis C virus genotype and viral load determination using Amplicor GT HCV MONITOR test v2.0

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World Journal of Gastroenterology 2005年第4期11卷 469-475页

作者： Motokazu Mukaide Yasuhito Tanaka Hirokazu Kakuda kei fujiwara Fuat Kurbanov Eturo Orito Kentaro Yoshioka Kiyotaka Fujise Shoji Harada Takazumi Kozaki Kazuo Takemura Kazumasa Hikiji Masashi Mizokami SRL Inc. 5-6-50ShinmachiHino-shiTokyo 191-0002Japan Department of Clinical Molecular Informative Medicine Nagoya City University Graduate School of Medical Sciences KawasumiMizuhoNagoya 467-8601Japan Department of Internal Medicine and Molecular Science Nagoya City University Graduate School of Medical Sciences KawasumiMizuhoNagoya 467-8601Japan Department of Clinical Molecular Informative Medicine Nagoya City University Graduate School of Medical Sciences KawasumiMizuhoNagoya 467-8601 Japan Third Department of Internal Medicine Nagoya University School of Medicine65 TsurumaShowaNagoya 466-8550Japan Division of Gastroenterology and Hepatology Department of Internal Medicine (Kashiwa) The Jikei University School of Medicine163-1KashiwashitaKashiwaChiba 277-8567Japan SRL Inc. 5-6-50ShinmachiHmo-shiTokyo 191-0002Japan

AIM: To develop a new sensitive and inexpensive hepatitis C virus (HCV) combination test (HCV Guideline test) that enables the determination of HCV genotypes 1, 2 and 3, and simultaneous determination of HCV viral load using commercial Amplicor GT HOV MONITOR test v2.0 (microwell version). METHODS: The HCV Guideline test used the PCR product generated in commercial Amplicor GT HCV Monitor test v2.0 for viral load measurement using microwell plate version of Amplicor HCV Monitor and also captured on separate plates containing capture probes and competitive oligonucleotide probes specific for HCV genotypes 1, 2 and 3, The HCV genotype was subsequently determined using the biotin-labeled PCR product and five biotin-labeled HCV-specific probes. RESULTS: The sensitivity of the HCV Guideline test was 0.5 KIU/mL. Specificity of the HCV Guideline test was confirmed by direct sequencing of HCV core region and molecular evolutionary analyses based on a panel of 31 samples. The comparison of the HCV Guideline test and an in-house HCV core genotyping assay using 252 samples from chronic hepatitis C patients indicated concordant results for 97.2% of samples (59.5% genotype 1, 33.7% genotype 2, 6.0% genotype 3, and 0.8% mixed genotypes). Similarly, the HCV Guideline test showed concordance with a serological test, and the serological test failed to assign any serotype in 12.7% of the samples, indicating a better sensitivity of the HCV Guideline test. CONCLUSION: Clinically, both viral load and genotypes (1, 2 and 3) have been found to be major predictors of antiviral therapy outcome regarding chronic hepatitis C based on guidelines and they are, in normal circumstances, performed as separate stand-alone assays. The HCV Guideline test is a useful method for screening large cohorts in a routine clinical setting for determining the treatment regimen and for predicting the outcome of antiviral therapy of chronic hepatitis C.

关键词： Hepatitis CVirus HCV Guideline test Viral Load Genotype

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Distribution of HBV genotypes among HBV carriers in Benin:phylogenetic analysis and virological characteristics of HBV genotype E

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World Journal of Gastroenterology 2005年第41期11卷 6410-6415页

作者： kei fujiwara Yasuhito Tanaka Etsuro Orito Tomoyoshi Ohno Takanobu Kato Kanji Sugihara Izumi Hasegawa Mayumi Sakurai Kiyoaki Ito Atsushi Ozasa Yuko Sakamoto Isao Arita Ahmed El-Gohary Agossou Benoit Sophie I Ogoundele-Akplogan Namiko Yoshihara Ryuzo Ueda Masashi Mizokami Department of Internal Medicine and Molecular Science Nagoya City University Graduate School of Medical Sciences NagoyaJapan Department of Clinical Molecular Informative Medicine Nagoya City University Graduate School of Medical Sciences NagoyaJapan AIDS Research Center National Institute of Infectious Disease TokyoJapan Agency for Cooperation in International Health Kumamoto Japan Clinical Pathology Department Faculty of Medicine Suez Canal UniversityIsmailiaEgypt Central National Blood Transfusion Center Cotonou Benin Hematology Lab-CNHUC Cotonou Benin

AIM: To determine the distribution of Hepatitis B virus (HBV) genotypes in Benin, and to clarify the virological characteristics of the dominant ***: Among 500 blood donors in Benin, 21 HBsAg-positive donors were enrolled in the study. HBV genotypes were determined by enzyme immunoassay and restriction fragment length polymorphism. Complete genome sequences were determined by PCR and direct ***: HBV genotype E (HBV/E) was detected in 20/21 (95.2%), and HBV/A in 1/21 (4.8%). From the age-specific prevalence of HBeAg to anti-HBe seroconversion (SC) in 19 HBV/E subjects, SC was estimated to occur frequently in late teens in HBV/*** comparison of four complete HBV/E genomes from HBeAg-positive subjects in this study and five HBV/E sequences recruited from the database revealed that HBV/E was distributed throughout West Africa with very low genetic divers ity (nucleotide homology 96.7-99.2%).Based on the sequences in the basic core promoter (BCP)to precore region of the nine HBV/E isolates compared to those of the other genotypes, a nucleotide substitution in the BCP, G1757A, was observed in HBV/***: HBV/E is predominant in the Republic of Benin, and SC is estimated to occur in late teens in HBV/E. The specific nucleotide substitution G1757A in BCP, which might influence the virological characteristics,is observed in HBV/E.

关键词： HBV genotype West Africa Basic corepromoter

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Change in arterial tumor perfusion is an early biomarker of lenvatinib efficacy in patients with unresectable hepatocellular carcinoma

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World Journal of Gastroenterology 2019年第19期25卷 2365-2372页

作者： Hidekatsu Kuorda Tamami Abe Yudai fujiwara Takuya Okamoto Miki Yonezawa Hiroki Sato kei Endo Takayoshi Oikawa kei Sawara Yasuhiro Takikawa Division of Hepatology Department of Internal Medicine Iwate Medical University

BACKGROUND Lenvatinib is one of the first-line tyrosine kinase inhibitors used for unresectable hepatocellular carcinoma(HCC). In the present study, we evaluated the potential of early changes in the time-intensity curve(TIC) of arterial phase on contrastenhanced ultrasound(CEUS) as early imaging biomarkers of lenvatinib *** To evaluate the potential of the early changes in the TIC of CEUS as early imaging biomarkers of lenvatinib efficacy in patients with unresectable *** We analyzed 20 consecutive patients with unresectable HCC treated with lenvatinib from March to November 2018. Tumor response at 8 wk was assessed by computed tomography using the modified Response Evaluation Criteria in Solid Tumors(m RECIST). CEUS was performed at baseline before treatment(Day 0) and on day 7(Day 7), and the images were analyzed in the arterial phase for 20 seconds after the contrast agent arrived at the target tumor. Three perfusion parameters were extracted from the TICs: the slope of wash-in(Slope),time to peak(TTP) intensity, and the total area under the curve(AUC) during wash-in. The rate of change in the TIC parameters between Day 0 and Day 7 was compared between treatment responders and non-responders based on m *** The rate of change for all TIC parameters showed significant differences between the responders(n = 9) and non-responders(n = 11)(Slope, P = 0.025; TTP, P =0.004; and AUC, P = 0.0003). The area under the receiver operating curve values for slope, TTP, and AUC for the prediction of responders were 0.805, 0.869, and0.939, *** CEUS may be useful for the early prediction of tumor response to lenvatinib therapy in patients with unresectable HCC.

关键词： Hepatocellular carcinoma Lenvatinib Contrast-enhanced ultrasound Timeintensity curve

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Recent updates of therapeutic strategy of esophagogastric junction adenocarcinoma

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Journal of Cancer Metastasis and Treatment 2021年第1期7卷 727-736页

作者： Suguru Maruyama Yu Imamura Yasukazu Kanie kei Sakamoto Daisuke fujiwara Akihiko Okamura JunKanamori Masayuki Watanabe Department of Gastroenterological Surgery Cancer Institute Hospital of Japanese Foundation of Cancer ResearchTokyo 135-8550Japan.

The incidence of esophagogastric junction(EGJ)adenocarcinoma has been increasing in Asian *** the recent advances in multidisciplinary treatments,EGJ adenocarcinoma remains aggressive with unfavorable *** surgical strategy,EGJ adenocarcinoma arises between the esophagus and the stomach,and thus tumor cells spread through the lymphatic system both upward to the mediastinum and downward to the ***,an optimal extent of lymphadenectomy remains *** drug therapy,the latest topic in gastric and EGJ adenocarcinoma is trastuzumab deruxtecan,which is an antibody-drug conjugate consisting of an anti-HER2 *** addition,many clinical trials have recently demonstrated the efficacy of immune checkpoint ***,recent advances in sequencing technology have revealed that gastroesophageal adenocarcinoma could be categorized into four molecular subtypes:epstein-Barr virus-associated,high-level microsatellite instability,genomically stable,and chromosomal instability ***,these subtypes show distinct clinical phenotypes and molecular *** review the current surgical strategy and drug treatment such as molecular-targeted agents,immune checkpoint inhibitors,and molecular-subtype-based therapeutic strategies in EGJ *** and molecular characteristics and response to immune checkpoint inhibitors differ among molecular *** strategies based on molecular subtypes may be clinically beneficial for patients with EGJ adenocarcinoma.

关键词： Esophagogastric junction adenocarcinoma Barrett’s esophagus microsatellite instability molecular subtype

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Risk factors for bleeding after endoscopic mucosal resection

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World Journal of Gastroenterology 2005年第46期11卷 7335-7339页

作者： Masatsugu Shiba Kazuhide Higuchi Kaori Kadouchi Ai Montani Kazuki Yamamori Hirotoshi Okazaki Makiko Taguchi Tomoko Wada Atsushi Itani Toshio Watanabe Kazunari Tominaga Yoshihiro fujiwara Tomoshige Hayashi kei Tsumura Tetsuo Arakawa Department of GastroenterologyOsaka City University Medical School OsakaJapan Department of GastroenterologyOsaka City University Medical School OsakaJapan Department of Preventive Medicine and Environmental HealthOsaka City University Medical SchoolOsakaJapan Department of GastroenterologyOsaka City University Medical School OsakaJapan Department of CardiologyOsaka City University Medical SchoolOsakaJapan

AIM： To clarify the risk factors for bleeding after endoscopic mucosal resection （EMR）. METHODS： A total of 297 consecutive patients who underwent EMR were enrolled. Some of the patients had multiple lesions. Bleeding requiring endoscopic treatment was defined as bleeding after EMR. Odds ratios （OR） with 95% confidence intervals （CI）, calculated by logistic regression with multivariate adjustments for covariates, were the measures of association. RESULTS： Of the 297 patients, 57 （19.2%） patients with bleeding after EMR were confirmed. With multivariate adjustment, the cutting method of EMR, diameter, and endoscopic pattern of the tumor were associated with the risk of bleeding after EMR. The multivariate-adjusted OR for bleeding after EMR using endoscopic aspiration mucosectomy was 3.07 （95%CI, 1.59-5.92） compared with strip biopsy. The multiple-adjusted OR for bleeding after EMR for the highest quartile （16-50 mm） of tumor diameter was 5.63 （95%CI, 1.84-17.23） compared with that for the lowest （4-7 mm）. The multiple-adjusted OR for bleeding after EMR for depressed type of tumor was 4.21 （95%CI, 1.75-10.10） compared with elevated type. CONCLUSION： It is important to take tumor charactedstics （tumor size and endoscopic pattern） and cutting method of EMR into consideration in predicting bleeding after EMR.

关键词： Endoscopic mucosal resection Bleeding Tumor characteristics Cutting method

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