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Eiichi Ogawa,1 Norihiro Furusyo,1 Mindie H Nguyen2 1Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan; 2Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA Abstract: Tenofovir alafenamide (TAF), a novel prodrug of tenofovir (TFV), has been approved for the treatment of chronic hepatitis B virus (HBV) infection. TAF has been shown to be a potent inhibitor of HBV replication at a low dose, with high intracellular concentration and more than 90% lower systemic TFV concentration than tenofovir disoproxil fumarate (TDF). In two randomized, double-blind, multinational, Phase 3, non-inferiority trials for hepatitis B e antigen (HBeAg)-positive and -negative patients (primary analysis: 48 weeks), TAF 25 mg orally once-daily was not inferior to TDF 300 mg in achieving an HBV DNA level

Background The Wisteria floribunda agglutinin-positive human Mac-2-binding protein ( WFA+-M2 BP) is a new liver fibrosis glycobiomarker with unique fibrosis-related glyco-alteration. WFA+-M2 BP is also a useful surrogate marker for the risk of developing hepatocellular carcinoma and for the liver functional reserve. Aim To evaluate the diagnostic ability of WFA+-M2 BP for liver fibrosis in the clinical setting and the clinical utility of WFA+-M2 BP for predicting the efficacy of direct-acting anti-viral ( DAA) treatment for chronic hepatitis C patients. Methods The study included 159 genotype 1 hepatitis C patients who received DAA-based treatment (telaprevir or simeprevir) combined with pegylated-interferon alpha plus ribavirin (108 telaprevir- and 51 simeprevir-based triple treatment). The relation between baseline serum WFA+-M2 BP and treatment efficacy was evaluated. Results The serum WFA+-M2 BP level significantly increased with the progress of liver fibrosis. Area under the receiver operating characteristic curve analysis identified 2.17 as the cut-off index ( COI) for WFA+-M2 BP for diagnosing advanced fibrosis. The sustained virological response ( SVR) rate was significantly, negatively correlated with the serum WFA+-M2 BP level. Multiple logistic regression analysis found a low serum WFA+-M2 BP level (<2.17 COI) to be independently associated with SVR (odds ratio, 4.35, P = 0.027). Even for prior nonresponders and patients with the interleukin-28B minor allele or histological advanced fibrosis, treatment outcome was favourable for patients with a low serum WFA+-M2 BP level. Conclusion Serum WFA+-M2 BP is a non-invasive liver fibrosis marker useful for predicting the efficacy of DAA-based triple therapy for chronic hepatitis C patients. [ABSTRACT FROM AUTHOR]

Objectives: To assess the utility of Helicobacter pylori antibody testing, we evaluated the correlation between the H. pylori antibody titre and H. pylori -associated pathogenicity and the changes in antibody titre after H. pylori eradication therapy., Design: A retrospective observational cohort study., Setting and Participants: From 2004 to 2016, medical check-ups were performed in different regions of Japan. In total, 324 subjects infected with H. pylori who received H. pylori eradication therapy were enrolled; H. pylori was eradicated in 266 of these subjects. We examined the associations between H. pylori antibody titre with pepsinogen and the presence or absence of H. pylori -associated pathogenic proteins, such as cytotoxin-associated gene A and vacuolating cytotoxin gene A, at baseline and after H. pylori eradication therapy., Results: The H.pylori antibody titre showed a positive correlation with pepsinogen II and a negative correlation with the pepsinogen I/II ratio. Moreover, the H.pylori antibody titre significantly correlated with the positive rates of H. pylori -associated pathogenic protein before eradication therapy. Antibody titres decreased after eradication, the pepsinogen I/II ratio increased and the H. pylori -associated pathogenic protein-positive rate decreased in patients with successful eradication. The determination of eradication using the decline in antibody titre 6 months after eradication therapy was useful (area under the receiver operating characteristic curve: 0.98)., Conclusions: Our data indicate that the H. pylori antibody titre may represent the degree of pathogenicity. The H. pylori antibody titre was associated with attenuation of pathogenicity in patients with H. pylori eradication, indicating the clinical utility of H. pylori antibody testing., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: As practice patterns and hepatitis C virus (HCV) genotypes (GT) vary geographically, a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal. This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs, focusing on GT3 and GT6., Methods: We analyzed the sustained virological response (SVR12) of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific, North America, and Europe between 07/01/2014-07/01/2021., Results: The mean age was 62±13 years, with 49.6% male. The demographic breakdown was 91.1% Asian (52.9% Japanese, 25.7% Chinese/Taiwanese, 5.4% Korean, 3.3% Malaysian, and 2.9% Vietnamese), 6.4% White, 1.3% Hispanic/Latino, and 1% Black/African-American. Additionally, 34.8% had cirrhosis, 8.6% had hepatocellular carcinoma (HCC), and 24.9% were treatment-experienced (20.7% with interferon, 4.3% with direct-acting antivirals). The largest group was GT1 (10,246 [64.6%]), followed by GT2 (3,686 [23.2%]), GT3 (1,151 [7.2%]), GT6 (457 [2.8%]), GT4 (47 [0.3%]), GT5 (1 [0.006%]), and untyped GTs (261 [1.6%]). The overall SVR12 was 96.9%, with rates over 95% for GT1/2/3/6 but 91.5% for GT4. SVR12 for GT3 was 95.1% overall, 98.2% for GT3a, and 94.0% for GT3b. SVR12 was 98.3% overall for GT6, lower for patients with cirrhosis and treatment-experienced (TE) (93.8%) but ≥97.5% for treatment-naive patients regardless of cirrhosis status. On multivariable analysis, advanced age, prior treatment failure, cirrhosis, active HCC, and GT3/4 were independent predictors of lower SVR12, while being Asian was a significant predictor of achieving SVR12., Conclusions: In this diverse multinational real-world cohort of patients with various GTs, the overall cure rate was 96.9%, despite large numbers of patients with cirrhosis, HCC, TE, and GT3/6. SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent (>91%)., Competing Interests: FJ: Speaker fees: Gilead Sciences, MSD, and Ascletis. Consultancy: Gilead Sciences, MSD. FJ has been an Editorial Board Member of Journal of Clinical and Translational Hepatology since 2023. YJW: Speaker fees: Gilead Science, AbbVie. Research Grant: Medicine Academic Clinical Program, SingHealth, Singapore. YJW has been an Editorial Board Member of Journal of Clinical and Translational Hepatology since 2020. HT: Speaker fees: Gilead Science, AbbVie, Eisai, Fujifilm WAKO, Takeda, Kowa, Terumo, Astra Zeneca. VWSW: Consultancy: AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Inventiva, Novo Nordisk, Pfizer, Sagimet Biosciences, TARGET PharmaSolutions, Visirna. Speaker fees: Abbott, AbbVie, Gilead Sciences, Novo Nordisk, Unilab. Research grants: Gilead Sciences. Stock: Co-founder of Illuminatio Medical Technology Limited. MA: Speakers’ fees: AbbVie, Gilead Sciences. SD: Speakers fees: Gilead Sciences. MFY: Speakers’ fees: Fujirebio Incorporation, Gilead Sciences, Roche, Sysmex Corporation. Consulting or advisory board: AbbVie, Abbott Diagnostics, Aligos Therapeutics, AiCuris, Antios Therapeutics, Arbutus Biopharma, Arrowhead Pharmaceuticals, Assembly Biosciences, Clear B Therapeutics, Dicerna Pharmaceuticals, Finch Therapeutics, Fujirebio Incorporation, GlaxoSmithKline, Gilead Sciences, Immunocore, Janssen, Precision BioSciences, Roche, Sysmex Corporation, Tune Therapeutics, Vir Biotechnology and Visirna Therapeutics. Research grant: AbbVie, Assembly Biosciences, Arrowhead Pharmaceuticals, Fujirebio Incorporation, Gilead Sciences, Immunocore, Sysmex Corporation and Roche. MFY has been an Associate Editor of Journal of Clinical and Translational Hepatology since 2021. CW: Research grant: Gilead Sciences. MLYu: Research support (grant) from Abbvie, BMS, Gilead, Merck, and Roche diagnostics. Consultant of Abbvie, BMS, Gilead, Roche, and Roche diagnostics. Speaker of Abbvie, BMS, Eisai, Gilead, Roche, and Roche diagnostics. MLYu has been an Associate Editor of Journal of Clinical and Translational Hepatology since 2023. MHN: Research grants via institution: Pfizer, Enanta, Astra Zeneca, GSK, Delfi, Innogen, Exact Science, CurveBio, Gilead, Vir Biotech, Helio Health, National Cancer Institute, Glycotest. Consulting/Advisory board: Intercept, Exact Science, Gilead, GSK. JL, MLYe, WLC and JFH have been Editorial Board Members of Journal of Clinical and Translational Hepatology since 2022. HR has been an Editor-in-Chief of Journal of Clinical and Translational Hepatology since 2013. The other authors have no conflict of interests related to this publication., (© 2024 Authors.)

Background: Data on patients switched to tenofovir alafenamide (TAF) from nucleos(t)ide analogues (NUCs) other than tenofovir disoproxil fumarate are limited., Aims: To assess the treatment and renal/bone safety outcomes following the switch to TAF., Methods: We prospectively enrolled adult patients with chronic hepatitis B (CHB) who switched from any NUC to TAF at 14 centres in Japan, Korea, Taiwan and the U.S. Study outcomes were viral suppression (VR; HBV DNA < 20 IU/mL), biochemical response (BR; alanine aminotransferase normalisation), and changes in estimated glomerular filtration rate (eGFR) and T-scores (L-spine) by bone absorptiometry by 24 months after switch to TAF., Results: We enrolled 270 eligible patients. Mean age was 58.1; 58.2% were male; 12.2% had cirrhosis and 73.3% previously received entecavir monotherapy. VR rate increased significantly from 95.2% to 98.8% by 24 months after the switch to TAF (p = 0.014). Between the switch and 24 months later, the mean spine T-score improved significantly from -1.43 ± 1.36 to -1.17 ± 1.38 (p < 0.0001), while there was no significant change in mean eGFR (88.4 ± 16.9-89.5 ± 16.3 mL/min/1.73 m 2 , p = 0.13). On multivariable analysis adjusted for age, sex, baseline spine T-score and prior TDF or adefovir dipivoxil use, male sex was significantly associated with lower risk of worsening spine T-score (odds ratio: 0.29, p = 0.020), while age was significantly associated with a higher risk of worsening chronic kidney disease stage (OR: 1.07, p = 0.019)., Conclusions: At 24 months after the switch to TAF, VR rates and spine bone density improved significantly while renal function remained stable., (© 2023 John Wiley & Sons Ltd.)

Background: Tenofovir alafenamide (TAF) may be preferable to other nucleos(t)ide analogues (NA) regarding outcomes against chronic hepatitis B virus (HBV) infection., Aims: To evaluate the longer term virological/biochemical effectiveness of TAF and the renal safety of sequential therapy to TAF in real-world settings METHODS: This multi-centre, retrospective cohort study included consecutive adult patients who were switched from other NAs to TAF. We assessed the virological and biochemical responses up to 144 weeks. We performed sensitivity analyses for a subgroup with chronic kidney disease (CKD) at baseline., Results: We analysed the data of 391 patients with chronic hepatitis B previously treated with entecavir (ETV) (n = 174), tenofovir disoproxil fumarate (TDF) (n = 116) or an NA combination (n = 101) for ≥ 24 months. HBV DNA <10 IU/ml at week 144 was found for 99% of patients, regardless of prior NA regimen or HBV DNA level at baseline. For patients who switched from TDF to TAF, total, low-density lipoprotein, high-density lipoprotein cholesterol and triglycerides were significantly increased after the switch. Patients who switched from a nucleotide analogue to TAF had an improved estimated glomerular filtration rate, although the rate of hypophosphataemia (<2.5 mg/dl) remained 9.7% at week 144. The virological and biochemical responses of patients with CKD were similar to the overall results., Conclusions: Switching to TAF remained effective and safe for up to 3 years. Given the increasing comorbidities related to ageing, it will be important to carefully follow the change in the lipid levels of patients with a prior TDF-based regimen., (© 2022 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background: The bioactivities of commensal duodenal microbiota greatly influence the biofunction of hosts. We investigated the role of Helicobacter pylori infection in extra-gastroduodenal diseases by determining the impact of H. pylori infection on the duodenal microbiota. We sequenced 16 S rRNA genes in samples aspirated from the descending duodenum of 47 (male, 20; female, 27) individuals who were screened for gastric cancer. Samples were analysed using 16 S rRNA gene amplicon sequencing, and the LEFSe and Kyoto Encyclopaedia of Genes and Genomes methods were used to determine whether the duodenal microflora and microbial biofunctions were affected using H. pylori infection., Results: Thirteen and 34 participants tested positive and negative for H. pylori, respectively. We identified 1,404 bacterial operational taxonomic units from 23 phyla and 253 genera. H. pylori infection changed the relative mean abundance of three phyla (Proteobacteria, Actinobacteria, and TM7) and ten genera (Neisseria, Rothia, TM7-3, Leptotrichia, Lachnospiraceae, Megasphaera, F16, Moryella, Filifactor, and Paludibacter). Microbiota features were significantly influenced in H. pylori-positive participants by 12 taxa mostly classified as Gammaproteobacteria. Microbial functional annotation revealed that H. pylori significantly affected 12 microbial metabolic pathways., Conclusions: H. pylori disrupted normal bacterial communities in the duodenum and changed the biofunctions of commensal microbiota primarily by upregulating specific metabolic pathways. Such upregulation may be involved in the onset of diseases associated with H. pylori infection., (© 2022. The Author(s).)

Purpose: The Kyushu and Okinawa Population Study (KOPS) was established to investigate gene-environmental interactions in non-communicable diseases in Japan. Besides collecting blood samples and anthropometric measurements, we also obtained medical histories, psychological status and lifestyle habits, including physical activities and dietary patterns., Participants: KOPS is a community-based prospective cohort study and consists of participants from four southwestern areas in Japan. Baseline surveys were conducted between 2004 and 2007 (wave 1), and 2009 and 2012 (wave 2) at the sites of municipality-based health check-ups. A total of 17 077 participants were included, comprising 10 697 participants of wave 1 and 6380 participants of wave 2; the median age in both groups was 61 years. Among them, 3006 individuals participated in both wave 1 and wave 2 surveys., Findings to Date: We have focused on either risk or confounding factors for non-communicable diseases. We have assessed the clinical utility of the newly developed biomarkers for impaired glucose tolerance, such as urinary myo-inositol and glycated albumin, and atherosclerosis, such as small dense low-density lipoprotein cholesterol. We have conducted an international collaborative study with Framingham Offspring Study to investigate ethnic differences in impaired glucose tolerance and cardiovascular diseases. We have found that insulin resistance and deficiency might account for the ethnic differences in impaired glucose tolerance and cardiovascular disease risks. As gene-environmental interaction analyses, we found a synergic effect of interleukin 28B single nucleotide polymorphisms (SNPs) and gender on the spontaneous elimination of hepatitis C, and a beneficial interaction of SNPs of high-density lipoprotein cholesterol and gender on the impact of physical activity. In addition, we reported eight novel loci contributing to the development and severity of coronary artery disease from a large genome-wide association study., Future Plans: We plan to investigate further the clinical utility of the newly developed biomarkers and the gene-environmental interactions using prospective data., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The Japan Multi-institutional Collaborative Cohort (J-MICC) study was launched in 2005 to examine gene-environment interactions in lifestyle-related diseases, including cancers, among the Japanese. This report describes the study design and baseline profile of the study participants., Methods: The participants of the J-MICC Study were individuals aged 35 to 69 years enrolled from respondents to study announcements in specified regions, inhabitants attending health checkup examinations provided by local governments, visitors at health checkup centers, and first-visit patients at a cancer hospital in Japan. At the time of the baseline survey, from 2005 to 2014, we obtained comprehensive information regarding demographics, education, alcohol consumption, smoking, sleeping, exercise, food intake frequency, medication and supplement use, personal and family disease history, psychological stress, and female reproductive history and collected peripheral blood samples., Results: The baseline survey included 92,610 adults (mean age: 55.2 [standard deviation, 9.4] years, 44.1% men) from 14 study regions in 12 prefectures. The participation rate was 33.5%, with participation ranging from 19.7% to 69.8% in different study regions. The largest number of participants was in the age groups of 65-69 years for men and 60-64 years for women. There were differences in body mass index, educational attainment, alcohol consumption, smoking, and sleep duration between men and women., Conclusions: The J-MICC Study collected lifestyle and clinical data and biospecimens from over 90,000 participants. This cohort is expected to be a valuable resource for the national and international scientific community in providing evidence to support longer healthy lives.

We evaluated the changes of gadoxetic acid uptake of the liver parenchyma after hepatitis C virus (HCV) eradication by direct-antiviral agent (DAA) therapy. The increase rate of the liver-to-muscle signal intensity ratio, the skewness and the kurtosis were calculated in the hepatobiliary phase. After sustained virological response, gadoxetic acid uptake of the liver parenchyma increased, but became heterogeneous. Our study proved that HCV eradication by DAA therapy could significantly affect gadoxetic acid uptake.

Aim: The association between small dense low-density lipoprotein cholesterol (sdLDL-C) levels and carotid intimal medial thickness (cIMT) progression has not been evaluated fully. We assessed specialized lipoproteins, including sdLDL-C, with regard to cIMT progression in a prospective observational study in Japan., Methods: Plasma total cholesterol, direct LDL-C, sdLDL-C, LDL-triglycerides (LDL-TG), high-density lipoprotein cholesterol (HDL-C), HDL2-C, HDL3-C, triglycerides, Lp(a), and adiponectin were measured in 2,030 men and women (median age 59 years, free of cardiovascular disease (CVD) and off cholesterol lowering medication). At both baseline and after a five-year follow-up, cIMT was assessed. Univariate, multivariate regression, and least square analyses were performed to examine the relationships between direct LDL-C, sdLDL-C, and other lipoproteins with cIMT progression., Results: The median cIMT at baseline was 0.63 mm and five-year progression was 0.18 mm. After adjustment for standard CVD risk factors, including age, gender, systolic blood pressure, total cholesterol, HDL-C, smoking, diabetes, and hypertension treatment, only direct LDL-C, sdLDL-C, and the sdLDL-C/LDL-C ratio were associated with cIMT progression. Even in subjects with direct LDL-C ＜100 mg/dL, who were considered at low CVD risk, elevated sdLDL-C were associated with cIMT progression (P for trend=0.009) in a model with established CVD risk factors, although the sdLDL-C/LDL-C ratio did not. Those correlations did not change by including triglycerides as a controlling factor or excluding premenopausal women from the analyzed population., Conclusions: Small dense LDL-C has a stronger relationship with cIMT progression than LDL-C does; therefore, measuring sdLDL-C may allow for the formulation of optimal therapy for CVD prevention.

Advanced fibrosis/cirrhosis and related biomarkers have been recognized as useful predictors of the development of hepatocellular carcinoma (HCC) by patients with chronic hepatitis C (CHC) following hepatitis C virus (HCV) cure by direct-acting antivirals (DAAs). However, it remains unclear if DAAs themselves have an influence on or facilitate the development of HCC. This multicenter cohort study included CHC patients without a history of HCC who achieved HCV elimination by DAAs. Cohorts of 835 patients treated with a sofosbuvir (SOF)-based regimen and 835 treated with a SOF-free regimen were matched 1:1 by propensity scoring with nine variables to evaluate differences in HCC incidence. The median observation period was 3.5 years. Sixty-nine cases of HCC were found during 5483.9 person-years (PY) over the entire follow-up period. The annual incidence was similar for both groups (SOF-based 1.25 and SOF-free 1.27 per 100 PY, respectively: adjusted hazard ratio (HR) 1.26, 95% confidence interval (CI) 0.75-2.12, p = 0.39). However, the annual incidence within the first two years was higher for patients treated with SOF than for those without, but did not reach significance (1.50 and 0.97 per 100 PY incidence rates, respectively: adjusted HR 2.05, 95% CI 0.98-4.25, p = 0.06). In summary, DAA treatment with SOF was not associated with an increase in the development of de novo HCC.

Few studies have investigated the interactions between HDL-C-related SNPs identified by genome-wide association (GWA) study and physical activity (PA) on HDL-C. First, we conducted a sex-stratified GWA study in a discovery sample (2,231 men and 2,431 women) and replication sample (2,599 men and 3,109 women) to identify SNPs influencing log-transformed HDL-C in Japanese participants in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. We also replicated previously reported HDL-C-related SNPs in a combined (discovery plus replication) sample (4,830 men and 5,540 women). We then analyzed the interactions of the HDL-C-related SNPs with PA on HDL-C. The sex-stratified GWA analyses identified 11 and 10 HDL-C-related SNPs in men and women as targets for an interaction analysis. Among these, only one interaction of ABCA1 rs1883025 with PA was statistically significant in men, after Bonferroni correction [ P -interaction = 0.001 (α = 0.05/21 = 0.002)]. The per-major-allele (C allele) increase in log-transformed HDL-C was lost in men with low PA (β = 0.008) compared with those with medium (β = 0.032) or high PA (β = 0.034). These findings suggest that the benefit of carrying a C allele of ABCA1 rs1883025 on enhancing HDL-C may be attenuated in inactive men., (Copyright © 2020 Nishida et al.)

A 37-year-old woman presented to our hospital with mild abdominal pain experienced for 2 months and hepatic nodules in segments 3 and 8. Peripheral blood eosinophilia was observed, and toxocariasis was serologically diagnosed. Seventeen days after the first imaging evaluation, a new lesion was found in segment 9 of the right lung, which was contiguous through the diaphragm to the hepatic nodule in segment 8. After treatment with albendazole, the liver and lung nodules disappeared. We suspect that larvae had directly invaded the lung from the liver, through the diaphragm.

Background: Increases in circulating LDL cholesterol (LDL-C) and high-sensitivity C-reactive protein (hsCRP) concentrations are significant risk factors for cardiovascular disease (CVD). We assessed direct LDL-C and hsCRP concentrations compared to standard risk factors in the Framingham Offspring Study., Methods: We used stored frozen plasma samples (-80 °C) obtained after an overnight fast from 3147 male and female participants (mean age, 58 years) free of CVD at cycle 6 of the Framingham Offspring Study. Overall, 677 participants (21.5%) had a CVD end point over a median of 16.0 years of follow-up. Total cholesterol (TC), triglyceride (TG), HDL cholesterol (HDL-C), direct LDL-C (Denka Seiken and Kyowa Medex methods), and hsCRP (Dade Behring method) concentrations were measured by automated analysis. LDL-C was also calculated by both the Friedewald and Martin methods., Results: Considering all CVD outcomes on univariate analysis, significant factors included standard risk factors (age, hypertension, HDL-C, hypertension treatment, sex, diabetes, smoking, and TC concentration) and nonstandard risk factors (non-HDL-C, direct LDL-C and calculated LDL-C, TG, and hsCRP concentrations). On multivariate analysis, only the Denka Seiken direct LDL-C and the Dade Behring hsCRP were still significant on Cox regression analysis and improved the net risk reclassification index, but with modest effects. Discordance analysis confirmed the benefit of the Denka Seiken direct LDL-C method for prospective hard CVD endpoints (new-onset myocardial infarction, stroke, and/or CVD death)., Conclusions: Our data indicate that the Denka Seiken direct LDL-C and Dade Behring hsCRP measurements add significant, but modest, information about CVD risk, compared to standard risk factors and/or calculated LDL-C., (© 2019 American Association for Clinical Chemistry.)

Objectives: A number of publications have demonstrated the cost-effectiveness of sofosbuvir plus ribavirin (SOF+RBV) compared with the former standard therapy with interferon (IFN)-containing regimens. Unlike these cost-effective analyses, where efficacy parameters were obtained from registration trials for drug approval, this analysis is a cost-effectiveness analysis of SOF+RBV for genotype (GT) 2 non-cirrhosis (NC) and compensated cirrhosis (CC) patients using efficacy parameters obtained from a multicentre cohort study (Kyushu University Liver Disease Study; KULDS) in Kyushu area in Japan in order to reflect real-world clinical practice in Japan., Method: A Markov model followed 10 000 patients (62 years old) over their lifetime. Four populations were followed: treatment-naïve (TN)-NC, treatment-experienced (TE)-NC, TN-CC and TE-CC. Comparators were Peg-IFNα2b+RBV for TN-NC and CC patients and telaprevir (TVR)+Peg-IFNα2b+RBV for TE-NC patients. The sustained virological response (SVR) rates of SOF+RBV were taken from KULDS and those of comparators were obtained from systematic literature reviews. There were nine states (NC, CC, decompensated cirrhosis [DC], hepatocellular carcinoma [HCC], SVR [NC], SVR [CC], liver transplantation [LT], post-LT and death) in this model, and an increase in the progression rate to HCC due to ageing was also considered. The analysis was conducted from the perspective of a public healthcare payer, and a discount rate of 2% was set for both cost and effectiveness., Results: Incremental cost-effectiveness ratios (ICERs) of SOF+RBV versus Peg-IFNα2b+RBV were ¥323 928 /quality-adjusted life year (QALY) for TN-NC patients, ¥92 256/QALY for TN-CC patients and ¥1 519 202/QALY for TE-CC patients. The ICER of SOF+RBV versus TVR+Peg-IFNα2b+RBV was ¥849 138/QALY for TE-NC patients. The robustness of the results was determined by sensitivity analysis., Conclusions: The results of this analysis strongly demonstrate the robustness of our previous findings that SOF+RBV regimens are cost-effective in the real world and clinical trial settings for Japanese GT2 NC and CC patients., Competing Interests: Competing interests: AI received the research grants from Gilead Sciences K.K., for this study. He received grants from AbbVie GK., grants from Abbott Japan Inc., grants from Beckton Dickinson and Company, personal fees from Chugai Pharmaceuticals Inc., personal fees from Astellas Pharma Inc., grants from Eli Lilly Japan K.K., personal fees from CSL Behring Japan Inc., personal fees from Fuji film Inc., personal fees from Takeda Pharmaceutical Inc., grants from Milliman Inc., grants from Creativ-Ceuticals Inc., grants from PFIZER INC., grants from Intuitive Surgical G.K., personal fees from Sanofi Japan Inc., grants from Terumo corporation, outside the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

: The association between nutrient patterns and metabolic syndrome (MetS) has not been examined in a Japanese population. A cross-sectional study was performed on 30,108 participants (aged 35-69 years) in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. Dietary intake was assessed using a 46-item food frequency questionnaire. MetS was diagnosed according to the Joint Interim Statement Criteria of 2009, using body mass index instead of waist circumference. Factor analysis was applied to energy-adjusted intake of 21 nutrients, and three nutrient patterns were extracted: Factor 1 (fiber, potassium and vitamins pattern); Factor 2 (fats and fat-soluble vitamins pattern); and Factor 3 (saturated fatty acids, calcium and vitamin B 2 pattern). In multiple logistic regression analysis adjusted for sex, age, and other potential confounders, Factor 1 scores were associated with a significantly reduced odds ratio (OR) of MetS and all five components. Factor 2 scores were associated with significantly increased prevalence of MetS, obesity, and high blood pressure. Factor 3 scores were significantly associated with lower OR of MetS, high blood pressure, high serum triglycerides and low HDL cholesterol levels. Analysis of nutrient patterns may be useful to assess the overall quality of diet and its association with MetS., Competing Interests: The authors declare no conflict of interest.

Gout is a common arthritis caused by elevated serum uric acid (SUA) levels. Here we investigated loci influencing SUA in a genome-wide meta-analysis with 121,745 Japanese subjects. We identified 8948 variants at 36 genomic loci ( P <5 × 10 -8 ) including eight novel loci. Of these, missense variants of SESN2 and PNPLA3 were predicted to be damaging to the function of these proteins; another five loci- TMEM18 , TM4SF4 , MXD3-LMAN2 , PSORS1C1-PSORS1C2 , and HNF4A -are related to cell metabolism, proliferation, or oxidative stress; and the remaining locus, LINC01578 , is unknown. We also identified 132 correlated genes whose expression levels are associated with SUA-increasing alleles. These genes are enriched for the UniProt transport term, suggesting the importance of transport-related genes in SUA regulation. Furthermore, trans-ethnic meta-analysis across our own meta-analysis and the Global Urate Genetics Consortium has revealed 15 more novel loci associated with SUA. Our findings provide insight into the pathogenesis, treatment, and prevention of hyperuricemia/gout., Competing Interests: The authors declare no competing interests.

Genome-wide association studies (GWAS) have identified greater than 30 variants associated with ovarian cancer, but most of these variants were investigated in European populations. Here, we integrated GWAS and subsequent functional analyses to identify the genetic variants with potential regulatory effects. We conducted GWAS for ovarian cancer using 681 Japanese cases and 17,492 controls and found that rs137672 on 22q13.1 exhibited a strong association with a P-value of 1.05 × 10(-7) and an odds ratio of 0.573 with a 95% confidence interval of 0.466-0.703. In addition, three previously reported SNPs, i.e., rs10088218, rs9870207 and rs1400482, were validated in the Japanese population (P < 0.05) with the same risk allele as noted in previous studies. Functional studies including regulatory feature analysis and electrophoretic mobility shift assay (EMSA) revealed two regulatory SNPs in 22q13.1, rs2072872 and rs6509, that affect the binding affinity to some nuclear proteins in ovarian cancer cells. The plausible regulatory proteins whose motifs could be affected by the allele changes of these two SNPs were also proposed. Moreover, the protective G allele of rs6509 was associated with a decreased SYNGR1 expression level in normal ovarian tissues. Our findings elucidated the regulatory variants in 22q13.1 that are associated with ovarian cancer risk., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Although several genetic factors may play a role in leisure-time exercise behavior, there is currently no evidence of a significant genomewide association, and candidate gene replication studies have produced inconsistent results., Methods: We conducted a two-stage genomewide association study and candidate single-nucleotide polymorphisms (SNP) association study on leisure-time exercise behavior using 13,980 discovery samples from the Japan Multi-Institutional Collaborative Cohort (J-MICC) study, and 2036 replication samples from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center-2 study. Leisure-time physical activity was measured using a self-administered questionnaire that inquired about the type, frequency and duration of exercise. Participants with ≥4 MET·h·wk of leisure-time physical activity were defined as exhibiting leisure-time exercise behavior. Association testing using mixed linear regression models was performed on the discovery and replication samples, after which the results were combined in a meta-analysis. In addition, we tested six candidate genetic variants derived from previous genomewide association study., Results: We found that one novel SNP (rs10252228) located in the intergenic region between NPSR1 and DPY19L1 was significantly associated with leisure-time exercise behavior in discovery samples. This association was also significant in replication samples (combined P value by meta-analysis = 2.2 × 10). Several SNP linked with rs10252228 were significantly associated with gene expression of DPY19L1 and DP19L2P1 in skeletal muscle, heart, whole blood, and the nervous system. Among the candidate SNP, rs12612420 in DNAPTP6 demonstrated nominal significance in discovery samples but not in replication samples., Conclusions: We identified a novel genetic variant associated with regular leisure-time exercise behavior. Further functional studies are required to validate the role of these variants in exercise behavior.

Gastric cancer is the third leading cause of cancer mortality in Japan and worldwide. Although previous studies identify various genetic variations associated with gastric cancer, host genetic factors are largely unidentified. To identify novel gastric cancer loci in the Japanese population, herein, we carried out a large-scale genome-wide association study using 6171 cases and 27 178 controls followed by three replication analyses. Analysis using a total of 11 507 cases and 38 904 controls identified two novel loci on 12q24.11-12 (rs6490061, P = 3.20 × 10 -8 with an odds ratio [OR] of 0.905) and 20q11.21 (rs2376549, P = 8.11 × 10 -10 with an OR of 1.109). rs6490061 is located at intron 19 of the CUX2 gene, and its expression was suppressed by Helicobacter pylori infection. rs2376549 is included within the gene cluster of DEFB families that encode antibacterial peptides. We also found a significant association of rs7849280 in the ABO gene locus on 9q34.2 (P = 2.64 × 10 -13 with an OR of 1.148). CUX2 and ABO expression in gastric mucosal tissues was significantly associated with rs6490061 and rs7849280 (P = 0.0153 and 8.00 × 10 -11 ), respectively. Our findings show the crucial roles of genetic variations in the pathogenesis of gastric cancer., (© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Brief exposure to passive smoking immediately elevates blood pressure. However, little is known about the association between exposure to passive smoking and chronic hypertension. We aimed to examine this association in a cross-sectional study, after controlling multiple potential confounders.Participants included 32,098 lifetime nonsmokers (7,216 men and 24,882 women) enrolled in the Japan Multi-Institutional Collaborative Cohort Study. Passive smoking was assessed using a self-administered questionnaire. The single question about exposure to passive smoking had five response options: "sometimes or almost never," "almost every day, 2 hours/day or less," "almost every day, 2 to 4 hours/day," "almost every day, 4 to 6 hours/day," and "almost every day, 6 hours/day or longer." Hypertension was defined as any of the following: systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or use of antihypertensive medication. Multivariate-adjusted odds ratio (OR) and 95% confidence interval (CI) for hypertension were estimated by exposure level to passive smoking using unconditional logistic regression models.The multivariate-adjusted OR for hypertension in those exposed almost every day was 1.11 (95% CI: 1.03-1.20) compared with those exposed sometimes or almost never. The OR for a 1-hour per day increase in exposure was 1.03 (95% CI: 1.01-1.06, Pfor trend = .006). This association was stronger in men than in women; the ORs were 1.08 (95% CI: 1.01-1.15, Pfor trend = .036) and 1.03 (95% CI: 1.00-1.05, Pfor trend = .055), respectively.Our findings suggest importance of tobacco smoke control for preventing hypertension.

Aim: To analyze associations among the serum endostatin level, renal function, and carotid atherosclerosis of healthy residents of Japan., Methods: Among 1,057 Japanese residents who attended free public physical examinations between 2010 and 2011, we evaluated the data of 648 healthy residents (200 men and 448 women, age 24 to 84 years) for whom the serum endostatin level and common carotid intima-media thickness (IMT) were measured. Renal function was assessed by estimated glomerular filtration rate (eGFR). Multiple linear regression analysis was done to determine the association of eGFR and serum endostatin level after adjustment for known covariates. Mediation analysis was done using Baron and Kenny's regression approach., Results: The median endostatin level was 63.7 ng/mL (interquartile range: 49.7-93.2). The mean eGFR was 78.4±14.8 mL/min/1.73m 2 . Univariate analysis showed that age (r=－0.37, P＜0.01), non current smoking (85.8±13.0 vs. 77.5±14.8 mL/min/1.73 m 2 , P＜0.01), hemoglobin A1c (r=－0.08, P=0.05), low-density lipoprotein-cholesterol (r=－0.13, P＜0.01), uric acid (r=－0.15, P＜0.01), carotid IMT (r=－0.11, P＜0.01), and log-transformed endostatin (r=－0.36, P＜0.01) were significantly associated with eGFR. In multiple linear regression analysis, log-transformed endostatin was significantly associated with eGFR (beta=－0.24, P＜0.01). While, carotid IMT was no longer significant. Mediation analysis showed serum endostatin level to be a mediator in the association between carotid IMT and eGFR., Conclusions: The association between carotid IMT and eGFR is mediated by the serum endostatin level of healthy individuals.

Background: Genotype 3 (GT3) is a common chronic hepatitis C (CHC) genotype in Asia. Direct-acting antiviral (DAA) regimens have high cure rates, but real-world results are limited for Asia., Aim: To determine the real-world effectiveness of DAAs for patients with CHC GT3 in Asia., Methods: A systematic search was performed in PubMed (including MEDLINE), Embase, and selected international meeting abstract repositories. Eligible studies were postmarketing observational studies from Asia with the primary outcome of sustained virological response 12 weeks after completion of treatment (SVR12)., Results: A total of 15 studies with 4230 patients yielded a pooled SVR12 of 92.7%. High heterogeneity ( I 2 =93.2%, P <0.0001) was noted. In subgroup analyses, patients with cirrhosis had 10.9% lower SVR12 than non-cirrhotic patients (88.6% vs 98.9%; P <0.0001) and contributed 69.5% of the heterogeneity. Prior treatment failure did not reduce the pooled SVR12 (treatment-naïve: 94.6%, 95% CI 91.3% to 96.7% vs treatment-experienced: 94.0%, 95% CI 77.5% to 98.6%; P =0.89). Twenty-four weeks of sofosbuvir+ribavirin dual therapy was the most commonly used regimen which led to similar SVR12 (OR=1.1, P =0.73) but lower adverse event rate than 12 weeks of sofosbuvir+ribavirin+pegylated interferon triple therapy., Conclusion: Sofosbuvir+ribavirin for 24 weeks is the most widely used and generally well-tolerated DAA therapy in Asia. However, its effectiveness is not optimal in GT3 patients with cirrhosis., Competing Interests: Competing interests: NF: grant/research support: MSD, Gilead Sciences, Bristol-Myers Squibb and Janssen Pharmaceuticals; speaker’s bureau: Gilead Sciences, MSD, Bristol Myers and Janssen Pharmaceuticals; advisory board: Gilead Sciences, AbbVie and Bristol-Myers Squibb. MHN: grant/research support: BK Kee Foundation, Asian Health Foundation, Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, National Cancer Institute, Pfizer Pharmaceutical; advisory board member or consultant: Dynavax Laboratories, Gilead Sciences, Intercept Pharmaceuticals, Alnylam Pharmaceutical, Bristol-Myers Squibb, Novartis Pharmaceutical and Janssen Pharmaceuticals.

Background: Sofosbuvir plus ribavirin (SOF+RBV) for 12 weeks is the standard treatment for chronic hepatitis C (CHC) genotype 2 (GT2) in most of Asia despite availability of new CHC medications. SOF-RBV real-world effectiveness has only been reported in small and/or single-centre studies. Our goal was to determine the real-world effectiveness of 12-week SOF+RBV therapy for CHC GT2 in Asia., Methods: A systematic search on PubMed and Embase was conducted through 30 June 2017. We identified full articles and conference proceedings of at least 10 adult patients with CHC GT2 treated with SOF+RBV for 12 weeks under real-world setting in Asia., Results: A total of 2208 patients from 13 studies were included. The pooled sustained virological response 12 weeks after the end of treatment (SVR12) was 95.8% (95% CI 94.6% to 96.9%) with non-significant heterogeneity (I 2 =34.4%). Anaemia (27.9%) was the most common adverse event (AE), with serious AEs in 2.0% and only 0.7% discontinued therapy prematurely. In subgroup analyses, patients with cirrhosis had 8.7% lower SVR12 than non-cirrhotic patients ( P <0.0001), and treatment-experienced patients had 7.2% lower SVR12 than treatment-naïve patients ( P =0.0002). Cirrhotic treatment-experienced patients had the lowest SVR12 at 84.5%. There were no significant differences in pooled SVR12 among patient subgroups: RBV dose reduction versus no dose reduction ( P =0.30); hepatocellular carcinoma (HCC) versus no HCC ( P =0.10); GT 2a versus 2b ( P =0.86); and <65 vs ≥65 years of age ( P =0.20)., Conclusions: SOF+RBV for 12 weeks was safe and effective for patients with CHC GT2 in Asia, although those with cirrhosis and prior treatment failure had a lower pooled SVR12 rate., Trial Registration Number: CRD42017067928., Competing Interests: Competing interests: RCC: grant/research support, Gilead Sciences. NF: grant/research support: MSD, Gilead Sciences, Bristol-Myers Squibb and Janssen Pharmaceuticals; speaker’s bureau: Gilead Sciences, MSD, Bristol Myers, and Janssen Pharmaceuticals; advisory board: Gilead Sciences, AbbVie and Bristol-Myers Squibb. MHN: grant/research support: BK Kee Foundation, Asian Health Foundation, Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceutical, National Cancer Institute, and Pfizer; pharmaceutical; advisory board member or consultant: Dynavax Laboratories, Gilead Sciences, Intercept Pharmaceuticals, Alnylam Pharmaceutical, Bristol-Myers Squibb, Novartis Pharmaceutical and Janssen Pharmaceutical.

Aim: The present large-scale Japanese population study was performed to evaluate the relation between the serum thyroid stimulating hormone (TSH) level and renal function., Methods: Out of 1,374 residents who participated in a free public physical examination between 2010 and 2011, we evaluated the data of 888 participants for whom the serum TSH level and estimated glomerular filtration rate (eGFR) were successfully measured. The participants were categorized into three groups based on TSH levels (normal TSH, ≤2.4; high-normal TSH, 2.5-4.4; and subclinical hypothyroid, ≥4.5 μIU/mL). Multiple linear regression analysis adjusted for cardiovascular risk factors was performed to determine the relationship between serum TSH level and renal function., Results: The mean±SD TSH level was 2.0±1.4 μIU/mL, and 75.9% (n=674) of the participants had normal, 17.9% (n=159) had high-normal, and 6.2% (n=55) had subclinical hypothyroid TSH levels. The mean eGFR significantly decreased with increased TSH levels (normal TSH, 79.3±14.1; high-normal TSH, 77.4±13.0; and subclinical hypothyroid, 72.3±12.2 mL/min/1.73 m 2 : P for trend ＜0.01). Multiple linear regression analysis extracted log-transformed TSH level as an independent factor correlated with eGFR in the high-normal TSH group (beta=-0.18, P=0.02)., Conclusions: Our findings demonstrated a significant correlation between serum TSH levels and eGFR in high-normal TSH participants. In healthy individuals, high-normal TSH levels indicate increased the risk of chronic kidney disease.

Coffee is one of the most widely consumed beverages worldwide, and its role in human health has received much attention. Although genome-wide association studies (GWASs) have investigated genetic variants associated with coffee consumption in European populations, no such study has yet been conducted in an Asian population. Here, we conducted a GWAS to identify common genetic variations that affected coffee consumption in a Japanese population of 11,261 participants recruited as a part of the Japan Multi-Institutional Collaborative Cohort (J-MICC) study. Coffee consumption was collected using a self-administered questionnaire, and converted from categories to cups/day. In the discovery stage (n = 6,312), we found 2 independent loci (12q24.12-13 and 5q33.3) that met suggestive significance (P < 1 × 10 -6 ). In the replication stage (n = 4,949), the lead variant for the 12q24.12-13 locus (rs2074356) was significantly associated with habitual coffee consumption (P = 2.2 × 10 -6 ), whereas the lead variant for the 5q33.3 locus (rs1957553) was not (P = 0.53). A meta-analysis of the discovery and replication populations, and the combined analysis using all subjects, revealed that rs2074356 achieved genome-wide significance (P = 2.2 × 10 -16 for a meta-analysis). These findings indicate that the 12q24.12-13 locus is associated with coffee consumption among a Japanese population.

A 39-year-old Japanese man presented to our hospital complaining of left chest pain and rash on the hands and feet. Plain thoracic computed tomography (CT) revealed multiple nodular shadows in the left lower lobe of the lung. A diagnosis of secondary syphilis was made based on the appearance of the rash and positive serologic tests for syphilis. The patient was started on amoxicillin but was switched to minocycline due to amoxicillin-induced rash on both forearms. Thoracic CT after five months of treatment revealed that the multiple lung nodular shadows had contracted, and secondary syphilis with pulmonary involvement was diagnosed.

Background: Polyarteritis nodosa (PAN) is a primary systemic necrotizing vasculitis with diffuse organ involvements, resulting in a high mortality rate due to multiple organ failure. Although the small bowel is the frequently targeted organ of PAN-associated vasculitis, rectal involvement is very rare, and only one case of rectal bleeding has been previously reported. The mortality rate of PAN with gastrointestinal (GI) perforation is reportedly much higher than that of without severe GI involvement. We herein report the first case of rectal perforation due to PAN, successfully managed with an adequate surgical intervention., Case Presentation: A 66-year-old woman with PAN had abdominal pain and melena with guarding. Computed tomography scan showed abdominal free air and bubbles in the rectal hematoma. We diagnosed it acute peritonitis, and emergency surgery was performed. After removing rectal hematoma and necrotic tissue, a huge lack of rectal wall spreading to the pelvirectal space was observed. In order to totally remove the necrotic tissue, abdominoperineal resection was needed. Together with histopathological examinations which showed neutrophils and fibrinous necrosis, we finally diagnosed rectal perforation due to PAN. At 19-month follow-up after surgery, she was still healthy with a stable disease of PAN., Conclusions: We herein reported the first case of successfully managed rectal perforation due to PAN. Early adequate surgical resection may be important for the case with rectal perforation.

Aim: Stroke is associated closely with vascular homeostasis, and several complex processes and interacting pathways, which involve various genetic and environmental factors, contribute to the risk of stroke. Although adrenomedullin (ADM) has a number of physiological and vasoprotective functions, there are few studies of the ADM receptor system in humans. The ADM receptor comprises a calcitonin-receptor-like receptor (CLR) and receptor activity-modifying proteins (RAMPs). We analyzed single nucleotide polymorphisms (SNPs) in the RAMP2 and CLR genes to determine their association with stroke in the light of gene-environment interactions., Methods: Using cross-sectional data from the Japan Multi-Institutional Collaborative Cohort Study in the baseline surveys, 14,087 participants from 12 research areas were genotyped. We conducted a hypothesis-based association between stroke prevalence and SNPs in the RAMP2 and CLR genes based on data abstracted from two SNPs in RAMP2 and 369 SNPs in CLR. We selected five SNPs from among the CLR variants (rs77035639, rs3815524, rs75380157, rs574603859, and rs147565266) and one RAMP2 SNP (rs753152), which were associated with stroke, for analysis., Results: Five of the SNPs (rs77035639, rs3815524, rs75380157, rs147565266, and rs753152) showed no significant association with obesity, ischemic heart disease, hypertension, dyslipidemia, and diabetes. In the logistic regression analysis, rs574603859 had a lower odds ratio (0.238; 95% confidence interval, 0.076-0.745, adjusted for age, sex, and research area) and the other SNPs had higher odds ratios for association with stroke., Conclusions: This was the first study to investigate the relationships between ADM receptor genes (RAMP2 and CLR) and stroke in the light of gene-environment interactions in human.

Aim: To examine the association between the serum endostatin levels and subclinical atherosclerosis independent of traditional risk factors in a healthy Japanese population., Methods: Among 1,057 residents who attended free public physical examinations between 2010 and 2011, we evaluated the data of 648 healthy residents for whom the serum endostatin level and common carotid intima-media thickness (IMT) were successfully measured., Results: The median endostatin level was 63.7 ng/mL (interquartile ranges: 49.7-93.2 ng/mL), and the mean carotid IMT was 0.68±0.12 mm. Residents with above median endostatin had significantly higher carotid IMT than did those with below median endostatin (0.71±0.14 vs. 0.65±0.09 mm, P＜0.001). Multiple linear regression analysis demonstrated that increased serum endostatin is significantly associated with carotid IMT (above vs. below median endostatin level; beta=0.11, P=0.03), independent of the known covariates of age, sex, body mass index, drinking and smoking status, systolic blood pressure, diastolic blood pressure, hemoglobin A1c, low density lipoprotein cholesterol, estimated glomerular filtration rate, and log-transformed high sensitive C-reactive protein., Conclusions: A higher serum endostatin level reflected subclinical atherosclerosis in this Japanese population.

Background: Helicobacter pylori infection is a known risk factor for duodenal ulcers, gastritis, and gastric cancer. The eradication of H. pylori is successful in treating these disorders; however, the success rate of eradication therapy is declining. There may be an interaction with nutrient intake to account for this decline. Objective: We investigated the influence of food and nutrient intake on H. pylori eradication therapy. Design: In this study, 4014 subjects underwent endoscopy, were tested for serum antibodies to H. pylori (2046 positive; 51.0%), and had their food intake assessed with the use of a food-frequency questionnaire (FFQ). Of the positive subjects, endoscopies showed that 389 (19.0%) had gastritis and/or duodenal ulcers and were also positive for a 13 C-urea breath test (UBT). These 389 subjects received 1-wk H. pylori eradication therapy with lansoprazole, amoxicillin, and clarithromycin and a second UBT 8 wk after treatment. Complete demographic characteristics, serum lipid, insulin, glycated hemoglobin, C-reactive protein (CRP), and creatinine concentrations as well as complete FFQs were available for 352 subjects. Multivariate logistic regression analyses were performed to determine factors that were associated with successful H. pylori eradication therapy. Results: The success rate of eradication therapy was 60.4% (235 of 389). Factors associated with the failure of eradication therapy included increased age ( P = 0.02), higher CRP concentrations ( P < 0.01), higher dietary cholesterol ( P < 0.01), higher ω-3 (n-3) fatty acid ( P < 0.01), higher ω-3 (n-3) fatty acid ( P = 0.02) or fish intake ( P = 0.01), and higher vitamin D intake ( P = 0.02). Moreover, the higher vitamin D intake was strongly linked to higher fish intake. A limitation of the study is that we did not assess the antibiotic resistance of H. pylori Conclusions: Our results indicate that higher egg and fish intake may be negatively correlated with successful H. pylori eradication therapy in H. pylori -positive subjects with gastritis and/or duodenal ulcers., (© 2017 American Society for Nutrition.)

We compared markers of glucose homeostasis and their association with diabetes and impaired fasting glucose (IFG) in Fukuoka, Japanese subjects (n = 1108) and age-, gender- and menopausal status-matched participants in the Framingham Offspring Study (n = 1096). The markers examined included fasting glucose, insulin, adiponectin, and glycated albumin, as well as body mass index (BMI), use of medications, and history of diabetes. The results showed that IFG prevalence in Japanese men (15.9%) and women (7.4%) were 50% less than those observed in Framingham men (34.5%) and women (21.4%) (P < 0.001). However, the diabetes prevalence in Japanese men at 13.3% was twice as high (P < 0.01) as the rate in Framingham men at 6.5%, while these rates were similar in women. Median insulin levels in Japanese men (4.6 μIU/mL) and women (4.3 μIU/mL) were about 50% lower (P < 0.001) than those in Framingham men (10.8 μIU/mL) and women (9.9 μIU/mL), as were insulin resistance values (P < 0.001). These population differences were also observed after subjects were stratified by glucose levels. In conclusion, our data indicate that there is significantly less IFG, lower insulin levels, and insulin resistance, but higher diabetes prevalence in Fukuoka men than in Framingham men, indicating that insulin deficiency may be an important cause of diabetes in Japan.

Aim: To evaluate the diagnostic performance of computed tomography (CT) volumetry for discriminating the fibrosis stage in patients with nonalcoholic fatty liver disease (NAFLD)., Methods: A total of 38 NAFLD patients were enrolled. On the basis of CT imaging, the volumes of total, left lateral segment (LLS), left medial segment, caudate lobe, and right lobe (RL) of the liver were calculated with a dedicated liver application. The relationship between the volume percentage of each area and fibrosis stage was analyzed using Spearman's rank correlation coefficient. A receiver operating characteristic (ROC) curve analysis was performed to determine the accuracy of CT volumetry for discriminating fibrosis stage., Results: The volume percentages of the caudate lobe and the LLS significantly increased with the fibrosis stage ( r = 0.815, P < 0.001; and r = 0.465, P = 0.003, respectively). Contrarily, the volume percentage of the RL significantly decreased with fibrosis stage ( r = -0.563, P < 0.001). The volume percentage of the caudate lobe had the best diagnostic accuracy for staging fibrosis, and the area under the ROC curve values for discriminating fibrosis stage were as follows: ≥ F1, 0.896; ≥ F2, 0.929; ≥ F3, 0.955; and ≥ F4, 0.923. The best cut-off for advanced fibrosis (F3-F4) was 4.789%, 85.7% sensitivity and 94.1% specificity., Conclusion: The volume percentage of the caudate lobe calculated by CT volumetry is a useful diagnostic parameter for staging fibrosis in NAFLD patients., Competing Interests: Conflict-of-interest statement: One author (Fujioka T) is an employee of Philips Electronics Japan.

Background: In Japanese Kampo medical practice, suidoku (fluid disturbance) is one of the most important concepts for selecting the proper medication. Suidoku is an excessive or uneven distribution of fluid that is indicated by splashing sounds and pitting edema. However, few objective reports about suidoku have been published. Bioelectrical impedance analysis (BIA) uses resistance values obtained from weak electrical currents to estimate body composition, including intracellular and extracellular water and muscle and fat mass. In this study, we used BIA to search for objective factors that can discriminate the various types of suidoku., Methods: Two hundred twenty-nine patients who visited the Kampo Medicine Clinic of Kyushu University Hospital from June 2010 to August 2015 were divided into non-suidoku (n = 180, 80 male and 100 female), splashing sound (n = 32, 8 male and 24 female) and edema groups (n = 17, 5 male and 12 female). Body composition values were taken from the electronic medical records of InBody730 (a vertical, segmental, multi-frequency analyzer by InBody, Tokyo Japan) testing done at the initial visit. Various parameters of the body composition values of female in the non-suidoku and suidoku groups (splashing sound and edema groups) were compared: there were too few male patients to provide significance., Results: The age and body weight were significantly lower in the splashing sound group than in the non-suidoku group (p < 0.05). In contrast, the body weight of the edema group was significantly heavier than that of the non-suidoku group (p < 0.05). In ROC analysis, the percent Body Fat ≤ 27.8 %, Muscle Mass Index of the Trunk ≤ 6.5 kg/m 2 , VFA (Visceral fat area) ≤ 5.4 and BMI ≤ 19.2 kg/m 2 were associated with splashing sound, and Muscle Mass Index of Legs ≥ 4.8 kg/m 2 and BMI ≥ 21.4 kg/m 2 were associated with edema., Conclusion: Our data suggest that the use of this type of BIA to estimate body composition would be a useful tool for the diagnosis of suidoku for women.