Language：English   Publishing type：Research paper (scientific journal)  

AIMS: The multisociety consensus nomenclature has introduced steatotic liver disease (SLD) with diverse subclassifications, which are metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-associated steatotic liver disease (MetALD), alcohol-associated liver disease (ALD), specific etiology, and cryptogenic. We investigated their prevalence, as per the new definition, in individuals undergoing health check-ups. Additionally, we analyzed the distribution of Fibrosis-4 (FIB-4) index and vibration-controlled transient elastography (VCTE)-derived liver stiffness measurement (LSM) for MASLD. METHODS: In this cross-sectional study, 6530 subjects undergoing a health check-up in Japan were included. Conventional B-mode ultrasound was carried out on all 6530 subjects, and those with MASLD underwent VCTE. RESULTS: The prevalence of SLD was 39.5%, comprising MASLD 28.7%, MetALD 8.6%, ALD 1.2%, specific etiology SLD 0.3%, and cryptogenic SLD 0.7%. Subjects with VCTE-derived LSM ≥8 kPa constituted 2.1% of MASLD. FIB-4 ≥1.3 showed that the sensitivity, specificity, positive predictive value (PPV), and negative predictive value for diagnosing VCTE-derived LSM ≥8 kPa were 60.6%, 77.0%, 5.3%, and 98.9%, respectively. The referral rate to specialists was 23.8% using FIB-4 ≥1.30. "FIB-4 ≥1.3 in subjects <65 years and FIB-4 ≥2.0 in subjects ≥65 years" showed higher PPV (6.7%) and lower referral rate (17.1%) compared with FIB-4 ≥1.3, but the sensitivity (54.5%) did not show adequate diagnostic capability as a noninvasive test for diagnosing VCTE-derived LSM ≥8 kPa. CONCLUSIONS: Acknowledging the selection bias in hepatology centers, we undertook this prospective health check-up study. Although the FIB-4 index proves to be a convenient marker, it might not perform well as a primary screening tool for liver fibrosis in the general population (UMIN Clinical Trials Registry No. UMIN000035188).

DOI： 10.1111/hepr.14117

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Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

Background and Objectives: The incidence of metabolic dysfunction-associated steatohepatitis (MASH)-related hepatocellular carcinoma (HCC) is increasing worldwide, alongside the epidemic of obesity and metabolic syndrome. Based on preliminary reports regarding the potential association of HCC and periodontitis, this study aimed to analyze the involvement of periodontal bacteria as well as the oral and intestinal bacterial flora in MASH-related HCC (MASH-HCC). Materials and Methods: Forty-one patients with MASH and nineteen with MASH-HCC participated in the study, completing survey questionnaires, undergoing periodontal examinations, and providing samples of saliva, mouth-rinsed water, feces, and peripheral blood. The oral and fecal microbiome profiles were analyzed by 16S ribosomal RNA sequencing. Bayesian network analysis was used to analyze the causation between various factors, including MASH-HCC, examinations, and bacteria. Results: The genus Fusobacterium had a significantly higher occupancy rate (p = 0.002) in the intestinal microflora of the MASH-HCC group compared to the MASH group. However, Butyricicoccus (p = 0.022) and Roseburia (p &lt; 0.05) had significantly lower occupancy rates. The Bayesian network analysis revealed the absence of periodontal pathogenic bacteria and enteric bacteria affecting HCC. However, HCC directly affected the periodontal bacterial species Porphyromonas gingivalis, Tannerella forsythia, Fusobacterium nucleatum, and Prevotella intermedia in the saliva, as well as the genera Lactobacillus, Roseburia, Fusobacterium, Prevotella, Clostridium, Ruminococcus, Trabulsiella, and SMB53 in the intestine. Furthermore, P. gingivalis in the oral cavity directly affected the genera Lactobacillus and Streptococcus in the intestine. Conclusions: MASH-HCC directly affects periodontal pathogenic and intestinal bacteria, and P. gingivalis may affect the intestinal bacteria associated with gastrointestinal cancer.

DOI： 10.3390/medicina60071150

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DOI： 10.3390/tomography10040036

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Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: Approved drug therapies for nonalcoholic steatohepatitis (NASH) are lacking, for which various agents are currently being tested in clinical trials. Effective drugs for liver fibrosis, the factor most associated with prognosis in NASH, are important. AREAS COVERED: This study reviewed the treatment of NASH with a focus on the effects of existing drugs and new drugs on liver fibrosis. EXPERT OPINION: Considering the complex pathophysiology of fibrosis in NASH, drug therapy may target multiple pathways. The method of assessing fibrosis is important when considering treatment for liver fibrosis in NASH. The Food and Drug Administration considers an important fibrosis endpoint to be histological improvement in at least one fibrosis stage while preventing worsening of fatty hepatitis. To obtain approval as a drug for NASH, efficacy needs to be demonstrated on endpoints such as liver-related events and myocardial infarction. Among the current therapeutic agents for NASH, thiazolidinedione, sodium-glucose co-transporter 2, and selective peroxisome proliferator-activated receptors α modulator have been reported to be effective against fibrosis, although further evidence is required. The effects of pan-peroxisome proliferator-activated receptors, obeticholic acid, and fibroblast growth factor-21 analogs on liver fibrosis in the development stage therapeutics for NASH are of particular interest.

DOI： 10.1080/14728214.2024.2328036

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BACKGROUND & AIMS: FibroScan® Expert 630 and FibroScan® Mini+430 are novel vibration-controlled transient elastography devices equipped with the same SmartExam software, which allows continuous measurement of controlled attenuation parameter (CAP) during the entire examination. This study aims to compare the CAP variabilities and the quantification for liver fibrosis and steatosis between the conventional FibroScan and the SmartExam-equipped machines in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: This retrospective study included 118 patients with biopsy-proven MASLD who underwent liver biopsy at two tertiary centres between 2021 and 2023. Liver stiffness and steatosis measurements were performed using both FibroScan machines and M and XL probes for each individual. Liver histology was used as the reference standard for liver fibrosis and steatosis staging. RESULTS: Standard deviations of continuous CAP (cCAP) were significantly lower than those of CAP for all probes (p < .0001). CAP variability was significantly associated with body mass index (p < .01), probe selection (p < .001) as well as the random effect of centre. Only the effect of probe selection (p < .001) was significantly associated with cCAP variability. No significant difference was found in the performance of staging liver fibrosis and steatosis between two types of machines at the same cut-offs. CONCLUSIONS: The SmartExam-based VCTE reduces the variability of CAP measurement and achieves a similar accuracy as the FibroScan 502 device for the estimation of both hepatic steatosis and fibrosis. Future studies should determine if cCAP is a better tool to monitor changes in steatosis than the original CAP.

DOI： 10.1111/liv.15862

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<h4>Background</h4>Cholesterol levels and bile acid metabolism are important drivers of metabolic dysfunction-associated steatohepatitis (MASH) progression. Using a mouse model, we investigated the mechanism by which cholesterol exacerbates MASH and the effect of colestyramine (a bile acid adsorption resin) and elobixibat (an apical sodium-dependent bile acid transporter inhibitor) concomitant administration on bile acid adsorption and MASH status.<h4>Methods</h4>Mice were fed a high-fat high-fructose diet with varying concentrations of cholesterol to determine changes in fatty liver according to liver status, water intake, defecation status, insulin resistance, bile acid levels, intestinal permeability, atherosclerosis (in apolipoprotein E knockout mice), and carcinogenesis (in diethylnitrosamine mice). Using small interfering ribonucleic acid (siRNA), we evaluated the effect of sterol regulatory element binding protein 1c (SREBP1c) knockdown on triglyceride synthesis and fatty liver status following the administration of elobixibat (group E), colestyramine (group C), or both (group EC).<h4>Results</h4>We found greater reductions in serum alanine aminotransferase levels, serum lipid parameters, serum primary bile acid concentrations, hepatic lipid levels, and fibrosis area in EC group than in the monotherapy groups. Increased intestinal permeability and watery diarrhea caused by elobixibat were completely ameliorated in group EC. Group EC showed reduced plaque formation rates in the entire aorta and aortic valve of the atherosclerosis model, and reduced tumor counts and tumor burden in the carcinogenesis model.<h4>Conclusions</h4>Excessive free cholesterol in the liver can promote fatty liver disease. Herein, combination therapy with EC effectively reduced free cholesterol levels in MASH model mice. Our study provides strong evidence for combination therapy as an effective treatment for MASH.

DOI： 10.1097/hc9.0000000000000285

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Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is the most common liver disease. It has a rapidly growing patient population owing to the increasing prevalence of obesity and type 2 diabetes. Patients with MASLD are primarily treated by family physicians when fibrosis is absent or mild and by gastroenterologists/hepatologists when fibrosis is more advanced. It is imperative that a system for the appropriate treatment and surveillance of hepatocellular carcinoma be established in order to ensure that highly fibrotic cases are not overlooked among the large number of MASLD patients. Family physicians should check for viral hepatitis, autoimmune hepatitis, alcoholic liver disease, and drug-induced liver disease, and should evaluate fibrosis using NIT; gastroenterologists/hepatologists should perform liver biopsy, ultrasound elastography (260 units in Japan as of October 2023), and MR elastography (35 units in Japan as of October 2023). This review presents the latest findings in MASLD and the role, accuracy, and clinical use of NIT. It also describes the collaboration between Japanese primary care and gastroenterologists/hepatologists in Japan in the treatment of liver diseases, including MASLD.

DOI： 10.3390/life13112144

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Drug-induced liver injury (DILI) is a major cause of acute liver injury, liver failure, and liver transplantation worldwide. In recent years, immune checkpoint inhibitors have become widely used. This has led to an increase in DILI, for which pathophysiology and management methods differ significantly from the past. As the number of cases of acute liver injury and liver transplantation due to DILI is expected to increase, information about a DILI is becoming more valuable. DILI is classified into two types according to its etiology: intrinsic DILI, in which the drug or its metabolites cause liver damage that is dose-dependent and predictable; and idiosyncratic DILI, in which liver damage is also dose-independent but unpredictable. In addition, depending on the course of the disease, chronic DILI or drug-induced autoimmune hepatitis may be present. The number of DILI cases caused by antimicrobial agents is decreasing, whereas that caused by drugs for malignant tumors and health foods is increasing. The Roussel Uclaf Causality Assessment Method is widely used to assess causality in DILI. Liver injury is a type of immune-related adverse event. The pattern of hepatic injury in immune-related adverse events is mostly hepatocellular, but mixed type and bile stasis have also been reported. Sclerosing cholangitis caused by immune checkpoint inhibitors has also been reported as a unique type of injury. Treatment mainly comprises withdrawal of immune checkpoint inhibitors and steroid administration; however, mycophenolate mofetil may be considered if the disease is refractory to steroids.

DOI： 10.14218/JCTH.2022.00067S

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BACKGROUND: The prognosis of metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly associated with liver fibrosis. We aimed to investigate whether liver stiffness measurement (LSM) and changes in LSM (ΔLSM) on magnetic resonance elastography (MRE) can predict clinical events in patients with MASLD. METHODS: We included 405 patients with MASLD who underwent at least two MREs. The patients were divided into five groups corresponding to fibrosis stages (0-4) based on initial LSM and classified as progressors (ΔLSM ≥ 19%) or non-progressors (ΔLSM < 19%) based on the difference between the first and last LSM. RESULTS: The mean follow-up period was 72.6 months, and the mean interval between MREs was 23.5 months. There were 52 (12.8%) progressors and 353 (87.2%) non-progressors. The initial LSM was significantly associated with the cumulative probabilities of decompensated cirrhosis, hepatocellular carcinoma (HCC), liver-related events, extrahepatic malignancies, and overall mortality but not with cardiovascular disease. Progressors had significantly higher hazard ratios (HRs) for decompensated cirrhosis, HCC, and liver-related events but not for extrahepatic malignancies, cardiovascular disease, or overall mortality. Among patients without cirrhosis, the HR for developing cirrhosis among progressors was 60.15. Progressors had a significantly higher risk of liver-related events, even in the low initial LSM (fibrosis stage 0-2) subgroups. CONCLUSIONS: Both initial LSM and ΔLSM can predict liver-related events in patients with MASLD, even for low initial LSM. This integrated assessment can allow more detailed risk stratification compared with single LSM assessments and identify high-risk patients with MASLD among those previously considered as low risk.

DOI： 10.1007/s00535-023-02049-9

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DOI： 10.21037/hbsn-23-342

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Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease, and there has been a rapid increase in cases worldwide. NAFLD is rapidly becoming the leading cause of hepatocellular carcinoma and is also associated with an increased risk of cardiovascular disease or exacerbation of other organ diseases, thus posing a significant health problem from both a medical and a socioeconomic perspective. NAFLD is a systemic disease and requires the involvement of numerous medical professionals. Multidisciplinary collaboration, in which different professionals within different specialties come together and work together toward a common goal, supports better patient care by integrating perspectives of multiple experts and facilitating the exchange of opinions. Due to the large number of potential patients, gastroenterologists and hepatologists cannot manage the patients alone, and collaboration between specialists in various fields, including family doctors, dentists, nutritionists, and pharmacists is required for treatment of NAFLD. This review will discuss NAFLD from the perspective of various specialties and introduce multidisciplinary collaboration.

DOI： 10.5009/gnl220545

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DOI： 10.1111/apt.17505

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BACKGROUND: Clinical trials enroll patients with active fibrotic non-alcoholic steatohepatitis (NASH) (NAFLD activity score≥4) and significant fibrosis (F≥2); however, screening failure rates are high following biopsy. We developed new scores to identify active fibrotic NASH using FibroScan and magnetic resonance imaging (MRI). METHODS: We conducted prospective primary (n=176), retrospective validation (n=169) and University of California San Diego (UCSD; n=234) studies of liver biopsy-proven NAFLD. Liver stiffness measurement (LSM) using FibroScan or magnetic resonance elastography (MRE), controlled attenuation parameter (CAP) or proton density fat fraction (PDFF), and AST were combined to develop two-step strategy-FibroScan-based LSM followed by CAP with AST (F-CAST) and MRE-based LSM followed by PDFF with AST (M-PAST)-and compared with FibroScan-AST (FAST) and MRI-AST (MAST) for diagnosing active fibrotic NASH. Each model was categorized using rule-in and rule-out criteria. RESULTS: Areas under receiver operating characteristic curves (AUROCs) of F-CAST (0.826) and M-PAST (0.832) were significantly higher than those of FAST (0.744, p=0.004) and MAST (0.710, p<0.001). Following the rule-in criteria, positive predictive values of F-CAST (81.8%) and M-PAST (81.8%) were higher than those of FAST (73.5%) and MAST (70.0%). Following the rule-out criteria, negative predictive values of F-CAST (90.5%) and M-PAST (90.9%) were higher than those of FAST (84.0%) and MAST (73.9%). In the validation and UCSD cohorts, AUROCs did not differ significantly between F-CAST and FAST, but M-PAST had a higher diagnostic performance than MAST. CONCLUSIONS: The two-step strategy, especially M-PAST, showed reliability of rule-in/-out for active fibrotic NASH, with better predictive performance compared with MAST. This article is protected by copyright. All rights reserved.

DOI： 10.1111/hepr.13927

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Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s12328-023-01789-8

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Other Link： https://link.springer.com/article/10.1007/s12328-023-01789-8/fulltext.html

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3390/app13063893

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The increasing incidence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), along with global lifestyle changes, requires further in-depth research to elucidate the mechanisms and develop new treatment strategies. In addition, the number of patients with periodontal disease has increased recently, suggesting that periodontal disease is sometimes associated with systemic conditions. In this review, we summarize recent studies linking periodontal disease and NAFLD, the concept of the mouth-gut-liver axis, oral and intestinal microbiota, and liver disease. We suggest new research directions toward a detailed mechanistic understanding and novel targets for treatment and prevention. Forty years have passed since the concepts of NAFLD and NASH were first proposed. however, no effective prevention or treatment has been established. We also found that the pathogenesis of NAFLD/NASH is not limited to liver-related diseases but has been reported to be associated with various systemic diseases and an increasing number of causes of death. In addition, changes in the intestinal microbiota have been shown to be a risk factor for periodontal diseases, such as atherosclerosis, diabetes, rheumatoid arthritis, nonalcoholic fatty liver disease, and obesity.

DOI： 10.3390/nu15051269

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

<h4>Aim</h4>We aimed to evaluate the diagnostic accuracy of the measurement of serum type IV collagen 7S (T4C7S) concentration for the staging of liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD).<h4>Methods</h4>A systematic literature search was performed using the PubMed, Cochrane Library, and Web of Science Core Collection databases for studies of the accuracy of serum T4C7S concentration for the staging of fibrosis using Fibrosis stage (F) 0-4 in patients with NAFLD diagnosed by liver biopsy.<h4>Results</h4>Nine articles describing 1,475 participants with NAFLD were included. For fibrosis ≥F1, with n=849, summary estimates of sensitivity of 0.79, specificity of 0.69, and area under the curve (AUC) of 0.80 were obtained using a median T7C4S cut-off value of 4.6 ng/ml. For fibrosis ≥F2, with n=1,090, summary estimates of sensitivity of 0.78, specificity of 0.78, and AUC of 0.84 were obtained using a median cut-off value of 4.9 ng/ml. For fibrosis ≥F3, with n=1,311 participants and a median cut-off value of 5.4 ng/ml, a pooled sensitivity of 0.82, specificity of 0.81, and AUC of 0.83 were obtained. For fibrosis ≥F4, with n=753 and a median cut-off value of 6.6 ng/ml, a pooled sensitivity of 0.85, specificity of 0.81, and AUC of 0.85 were obtained.<h4>Conclusions</h4>Serum T4C7S concentration was found to be an accurate method of staging liver fibrosis in patients with NAFLD. This article is protected by copyright. All rights reserved.

DOI： 10.1111/hepr.13857

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With the increasing incidence of non-alcoholic fatty liver disease (NAFLD) and the aging of the population, sarcopenia is attracting attention as one of the pathological conditions involved in the development and progression of NAFLD. In NAFLD, sarcopenia is closely associated with insulin resistance and results from the atrophy of skeletal muscle, an insulin target organ. In addition, inflammatory cytokines that promote skeletal muscle protein breakdown, low adiponectin levels leading to decreased insulin sensitivity, and hyperleptinemia are also involved in NAFLD pathogenesis. The presence of sarcopenia is a prognostic factor and increases the risk of mortality in patients with cirrhosis and post-treatment liver cancer. Sarcopenia, the presence of which mainly occurs due to decreased muscle mass, combined with increased visceral fat, can lead to sarcopenia-associated obesity, which increases the risk of NASH, liver fibrosis, and cardiovascular disease. In order to treat sarcopenia, it is necessary to properly evaluate sarcopenia status. Patients with high BMI, as in sarcopenic obesity, may improve with caloric restriction. However, inadequate oral intake may lead to further loss of muscle mass. Aerobic and resistance exercise should also be used appropriately.

DOI： 10.3390/nu15040891

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Non-invasive imaging techniques have greatly advanced the assessment of liver fibrosis and steatosis but are not fully evaluated in overweight patients. We evaluated the diagnostic performance of vibration-controlled transient elastography (VCTE) and magnetic resonance elastography (MRE) to assess fibrosis and controlled attenuation parameter (CAP) and MR imaging (MRI)-proton density fat fraction (MRI-PDFF) to assess steatosis in overweight and obese patients with non-alcoholic fatty liver disease (NAFLD). We included 163 biopsy-proven patients with NAFLD who underwent VCTE, MRE/MRI-PDFF, and liver biopsy (years 2014-2020) who were classified according to their body mass index (BMI) as normal (BMI < 25 kg/m2, n = 38), overweight (25 ≤ BMI < 30 kg/m2, n = 68), and obese (BMI ≥ 30 kg/m2, n = 57). VCTE and MRE detected fibrosis of stages ≥ 2, ≥ 3, and 4 with an area under the receiver operating curve (AUROC) of 0.83-0.94 (VCTE) and 0.85-0.95 (MRE) in all groups, without considerable differences. MRI-PDFF detected steatosis of grades ≥ 2 and 3 with high AUROC in all groups (0.81-1.00). CAP's diagnostic ability (0.63-0.95) was lower than that of MRI-PDFF and decreased with increasing BMI compared to MRI-PDFF. VCTE and MRE similarly accurately assess fibrosis, although MRI-PDFF is more accurate than CAP in detecting steatosis in overweight and obese patients with NAFLD.

DOI： 10.1038/s41598-022-25843-6

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Non-alcoholic fatty liver disease is currently the most common chronic liver disease, affecting up to 25% of the world's population. Simple fatty liver, in which fat is deposited in the liver without fibrosis, has been regarded as a benign disease in the past, but it is now known to be prognostic. In the future, more emphasis should be placed on the quantification of liver fat. Traditionally, fatty liver has been assessed by histological evaluation, which requires an invasive examination, but technological innovations have made it possible to evaluate fatty liver by noninvasive imaging methods such as ultrasonography, computed tomography, and magnetic resonance imaging. In addition, quantitative as well as qualitative measurements for the detection of fatty liver have become available. In this review, we summarize currently used qualitative evaluations of fatty liver and discuss quantitative evaluations that are expected to further develop in the future.

DOI： 10.3350/cmh.2022.0357

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BACKGROUND AND AIM: SmartExam is a novel computational method compatible with FibroScan that uses a software called SmartDepth and continuous controlled attenuation parameter measurements to evaluate liver fibrosis and steatosis. This retrospective study compared the diagnostic accuracy of conventional and SmartExam-equipped FibroScans for liver stiffness measurement (LSM). METHODS: The liver stiffness and the associated controlled attenuation parameters of 167 patients were measured using conventional and SmartExam-Equipped FibroScan as well as reference methods like magnetic resonance elastography (MRE) and magnetic resonance imaging-based proton density fat fraction measurements (MRI-PDFF) to assess its diagnostic performance. M or XL probes were selected based on the probe-to-liver capsule distance for all FibroScan examinations. RESULTS: The liver stiffness and controlled attenuation parameter (CAP) correlation coefficients calculated from conventional and SmartExam-equipped FibroScan were 0.97 and 0.82, respectively. Using MRE/MRI-PDFF as a reference and the DeLong test for analysis, LSM and the area under the receiver operating characteristic curve for CAP measured by conventional and SmartExam-equipped FibroScan showed no significant difference. However, the SmartExam-equipped FibroScan measurement (33.6 seconds) took 1.4 times longer than conventional FibroScan (23.2 seconds). CONCLUSIONS: SmartExam has a high diagnostic performance comparable to that of conventional FibroScan. Since the results of the conventional and SmartExam-equipped FibroScan were strongly correlated, it can be considered useful for assessing the fibrosis stage and steatosis grade of the liver in clinical practice, with less variability but little longer measurement time compared to the conventional FibroScan.

DOI： 10.1111/jgh.16076

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

A 2-step approach, Fibrosis-4 index (FIB-4) followed by vibration-controlled transient elastography (VCTE), has been proposed to predict advanced fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). We aimed to develop a novel 3-step approach for predicting advanced fibrosis. We enrolled 284 biopsy-confirmed NAFLD patients from two tertiary care centers and developed subgroups (n = 190), including 3.7% of patients with advanced fibrosis, assuming a primary care setting. In the 3-step approach, patients with intermediate-to-high FIB-4 in the first step underwent an enhanced liver fibrosis test or measurement of type IV collagen 7S domain as the second step, and VCTE was performed if the second step value was higher than the cutoff. In 284 cases, a tertiary care cohort with 36.3% advanced fibrosis, the 3-step approach showed significantly higher specificity and positive predictive value than the 2-step approach. In the subgroup with 3.7% advanced fibrosis, the 3-step approach significantly reduced the referral rate to specialists, the number of high-risk patients (i.e., liver biopsy candidates), and healthcare costs by 12.5% to 15.8%. The 3-step approach may improve the diagnostic performance to predict advanced fibrosis in NAFLD, which could lower rates of referrals to specialists, liver biopsies, and medical costs.

DOI： 10.1038/s41598-022-22767-z

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DOI： 10.3390/IJMS231911689

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1002/jgh3.12808

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Language：Japanese   Publisher：(NPO)日本歯周病学会  

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Language：Japanese   Publisher：日本消化器病学会-関東支部  

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DOI： 10.1136/BMJOPEN-2021-060335

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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DOI： 10.21037/HBSN-21-579

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INTRODUCTION: No reports on both blood and fecal bile acids (BAs) in patients with nonalcoholic fatty liver disease (NAFLD) exist. We simultaneously assessed the serum and fecal BA patterns in healthy participants and those with NAFLD. METHODS: We collected stools samples from 287 participants from 5 hospitals in Japan, (healthy control [HC]: n = 88, mild fibrosis: n = 104, advanced fibrosis group: n = 95). Blood samples were collected and analyzed for serum BAs and 7α-hydroxy-4-cholesten-3-one (C4)-a surrogate marker for BA synthesis ability-from 141 patients. Concentrations of BAs, including cholic acid (CA), deoxycholic acid (DCA), chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA), and lithocholic acid (LCA), were measured using liquid chromatography-mass spectrometry. RESULTS: Total fecal BA concentration was significantly higher in the NAFLD group with worsening of fibrosis than in the HC group. Most of the fecal BAs were secondary and unconjugated. In the fecal BA fraction, CA, DCA, CDCA, UDCA, and LCA were significantly higher in the NAFLD than in the HC group. The total serum BA concentration was higher in the NAFLD group with worsening of fibrosis than in the HC group. In the serum BA fraction, CA, LCA, and C4 concentrations were significantly higher in the NAFLD than in the HC group. DISCUSSION: Fecal and serum BA and C4 concentrations were high in patients with NAFLD with worsening of fibrosis, suggesting involvement of abnormal BA metabolism in NAFLD with fibrosis progression. Abnormalities in BA metabolism may be a therapeutic target in NAFLD with fibrosis.

DOI： 10.14309/ctg.0000000000000503

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DOI： 10.1002/hep4.1993

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BACKGROUND AND AIM: Liver stiffness measurement (LSM) and spleen stiffness measurement (SSM@50 Hz) using standard vibration-controlled transient elastography (VCTE) have been studied as a noninvasive test for screening of gastroesophageal varices (GEV) in chronic liver disease (CLD). Recently, a novel spleen-dedicated VCTE (SSM@100 Hz) has been developed. We evaluated the diagnostic performance of SSM@100 Hz, SSM@50 Hz, LSM, and other noninvasive tests using esophagogastroduodenoscopy (EGD) as the reference as well as the correlation with hepatic venous pressure gradient (HVPG). METHODS: A total of 123 patients with CLD enrolled in this cross-sectional study. SSM@100 Hz, SSM@50 Hz, and LSM were determined by VCTE. EGD and HVPG were performed within 12 weeks before or after VCTE. RESULTS: GEV were present in 60 patients. Failure or suboptimal SSM were fewer at 100 Hz (4.0%) than at 50 Hz (17.7%). All SSM values obtained at 100 Hz were lower than the 100 kPa ceiling threshold, but 10 patients reached the 75 kPa ceiling threshold for SSM@50 Hz. SSM@100 Hz was most accurate (area under the receiver operating characteristic [AUROC] = 0.944) for the diagnosis of GEV compared to SSM@50 Hz, LSM, and scoring systems. AUROC of SSM@100 Hz for diagnosis of high-bleeding risk varices (HRV) was 0.941, which was significantly higher than that of SSM@50 Hz (AUROC = 0.842, P = 0.002). SSM@100 Hz showed higher specificity (82.0%) for diagnosis of HRV than SSM@50 Hz (specificity = 67.1%). SSM@100 Hz was significantly correlated with HVPG (r = 0.71, P < 0.001). CONCLUSIONS: The novel spleen-dedicated VCTE examination can be used for noninvasive assessment of GEV and HVPG in CLD. Japan Registry of Clinical Trials Registry No. jRCTs032200119.

DOI： 10.1002/jgh3.12689

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DOI： 10.1002/HEP4.1993

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BACKGROUND AND AIMS: Despite that hepatic fibrosis often affects the liver globally, spatial distribution can be heterogeneous. This study aimed to investigate the effect of liver stiffness (LS) heterogeneity on concordance between MR elastography (MRE)-based fibrosis staging and biopsy staging in patients with NAFLD. APPROACH AND RESULTS: We retrospectively evaluated data from 155 NAFLD patients who underwent liver biopsy and 3 Tesla MRE and undertook a retrospective validation study of 169 NAFLD patients at three hepatology centers. Heterogeneity of stiffness was assessed by measuring the range between minimum and maximum MRE-based LS measurement (LSM). Variability of LSM was defined as the stiffness range divided by the maximum stiffness value. The cohort was divided into two groups (homogenous or heterogeneous), according to whether variability was below or above the average for the training cohort. Based on histopathology and receiver operating characteristic (ROC) analysis, optimum LSM thresholds were determined for MRE-based fibrosis staging of stage 4 (4.43, kPa; AUROC, 0.89) and stage ≥3 (3.93, kPa; AUROC, 0.89). In total, 53 had LSM above the threshold for stage 4. Within this group, 30 had a biopsy stage of <4. In 86.7% of these discordant cases, variability of LSM was classified as heterogeneous. In MRE-based LSM stage ≥3, 88.9% of discordant cases were classified as heterogeneous. Results of the validation cohort were similar to those of the training cohort. CONCLUSIONS: Discordance between biopsy- and MRE-based fibrosis staging is associated with heterogeneity in LSM, as depicted with MRE.

DOI： 10.1002/hep.32302

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Language：Japanese   Publisher：(一社)日本アルコール・アディクション医学会  

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Language：Japanese   Publisher：(株)南江堂  

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J00974&link_issn=&doc_id=20211203160010&doc_link_id=issn%3D0022-1961%26volume%3D128%26issue%3D6%26spage%3D1159&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0022-1961%26volume%3D128%26issue%3D6%26spage%3D1159&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction associated fatty liver disease (MAFLD) have important associations with cardiovascular disease (CVD). The main objective of this study was to compare the frequency of incidence rate of CVD in the NAFLD or MAFLD patients utilizing a large claims database. METHODS: Using the JMDC database from April 2013 to March 2019, we retrospectively analyzed data for 1,542,688 and 2,452,949 people to estimate the relationship between CVD and NAFLD, MAFLD, respectively. RESULTS: The incidence rates of CVD were 0.97 (95% CI 0.94-1.01) and 2.82 (95% CI 2.64-3.01) per 1000 person-years in the non-NAFLD and NAFLD groups, respectively, and 1.01 (95% CI 0.98-1.03) and 2.69 (95% CI 2.55-2.83) per 1000 person-years in the non-MAFLD and MAFLD groups, respectively. The overall prevalence of hypertriglyceridemia and diabetes mellitus (DM) was 13.1, and 4.2%, respectively, in the non-NAFLD group and 63.6, and 20.2%, respectively, in the NAFLD group. The overall prevalenceof hypertriglyceridemia and DM was 13.6 and 4.3%, respectively, in the non-MAFLD group and 64.1, and 20.6%, respectively, in the MAFLD group. HRs for CVD increased with hypertriglyceridemia and DM. CONCLUSIONS: Results indicated that incident rate of CVD increased with NAFLD/MAFLD; the complication rate of DM and hypertriglyceridemia among NAFLD/MAFLD patients is high and may affect the development of CVD.

DOI： 10.1007/s00535-021-01828-6

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BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic disease. SGL5213, which is minimally absorbed and is restricted to the intestinal tract, is a potent intestinal sodium-glucose cotransporter 1 (SGLT1) inhibitor. In this study, we investigated the protective effect of SGL5213 in a rodent model of NAFLD. METHODS: Using a rodent model of NAFLD, we compared SGL5213 efficacy with miglitol, which is an α-glucosidase inhibitor. We used a high-fat and high-sucrose diet-induced NAFLD model. RESULTS: SGL5213 and miglitol improved obesity, liver dysfunction, insulin resistance, and the NAFLD severity. To further investigate the effects of SGL5213, we analyzed the mRNA expression of genes involved in lipid metabolism, inflammation, and liver fibrosis, and cecal pH levels. SGL5213 and miglitol treatment significantly decreased mRNA expression of factors involved in inflammation and liver fibrosis. SGL5213 treatment significantly decreased cecal pH levels, which did not occur with miglitol. CONCLUSIONS: SGL5213 had a protective effect on the pathogenesis of NAFLD in a rodent model. We considered that inhibiting glucose absorption and increasing glucose content in the gastrointestinal tract with SGL5213 might have contributed to the protective effect in NAFLD. SGL5213 is a promising therapeutic agent for NAFLD with obesity and insulin resistance.

DOI： 10.1016/j.jphs.2021.07.002

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Language：Japanese   Publisher：(有)科学評論社  

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Language：Japanese   Publisher：医歯薬出版(株)  

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BACKGROUND AND AIM: Gut microbiota composition is associated with the pathogenesis of non-alcoholic fatty liver disease. However, the association between gut microbiota composition and non-alcoholic fatty liver disease in non-obese patients remains unclear. We compared clinical parameters and gut microbiota profiles of healthy controls and non-obese and obese patients with non-alcoholic fatty liver disease. METHODS: We examined the clinical parameters and gut microbiota profiles by 16S rRNA sequences and short-chain fatty acid levels in fecal samples from 51 non-obese patients with non-alcoholic fatty liver disease (body mass index <25 kg/m2 ) and 51 obese patients with non-alcoholic fatty liver disease (body mass index ≥30 kg/m2 ) who underwent pathological examination and 87 controls at five hospitals in Japan. RESULTS: Although no significant differences between the non-obese and other groups were observed in alpha diversity, a significant difference was found in beta diversity. We observed a significant decrease in serum alanine aminotransferase levels, Eubacterium population, and butyric acid levels in non-obese patients with non-alcoholic fatty liver disease compared with those in obese patients with non-alcoholic fatty liver disease. A significant negative correlation was found between the stage of hepatic fibrosis and Eubacterium abundance in non-obese patients with non-alcoholic fatty liver disease. CONCLUSIONS: The decrease in the abundance of Eubacterium that produces butyric acid may play an important role in the development of non-alcoholic fatty liver disease in non-obese individuals. This study was registered at the University Hospital Medical Information Network clinical trial registration system (UMIN000020917).

DOI： 10.1111/jgh.15487

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The liver directly accepts blood from the gut and is, therefore, exposed to intestinal bacteria. Recent studies have demonstrated a relationship between gut bacteria and nonalcoholic fatty liver disease (NAFLD). Approximately 10-20% of NAFLD patients develop nonalcoholic steatohepatitis (NASH), and endotoxins produced by Gram-negative bacilli may be involved in NAFLD pathogenesis. NAFLD hyperendotoxicemia has intestinal and hepatic factors. The intestinal factors include impaired intestinal barrier function (leaky gut syndrome) and dysbiosis due to increased abundance of ethanol-producing bacteria, which can change endogenous alcohol concentrations. The hepatic factors include hyperleptinemia, which is associated with an excessive response to endotoxins, leading to intrahepatic inflammation and fibrosis. Clinically, the relationship between gut bacteria and NAFLD has been targeted in some randomized controlled trials of probiotics and other agents, but the results have been inconsistent. A recent randomized, placebo-controlled study explored the utility of lubiprostone, a treatment for constipation, in restoring intestinal barrier function and improving the outcomes of NAFLD patients, marking a new phase in the development of novel therapies targeting the intestinal barrier. This review summarizes recent data from studies in animal models and randomized clinical trials on the role of the gut-liver axis in NAFLD pathogenesis and progression.

DOI： 10.3390/ijms22158161

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Cholestatic liver disease is a disease that causes liver damage and fibrosis owing to bile stasis. It is represented by primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), but the pathophysiological pathways that cause bile stasis in both diseases are different. The pathogenesis of the disease is still unclear, although autoimmune mechanisms have been postulated and partially elucidated. Although the disease may progress slowly with only mild liver dysfunction, it may progress to liver cirrhosis or liver failure, which require liver transplantation. As a medical treatment, ursodeoxycholic acid is widely used for PBC and has proved to be very effective against disease progression in cases of PBC. On the other hand, its efficacy is limited in cases of PSC, and the research and development of various drugs are underway. Furthermore, the clinical course of both diseases is quite variable, making the design of clinical trials fairly difficult. In this review, we present the general natural history of PBC and PSC, and provide information on the latest drug therapies currently available and those that are under investigation.

DOI： 10.1007/s40265-021-01545-7

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Language：Japanese   Publisher：(株)アークメディア  

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Lymphoepithelioma-like cholangiocarcinoma (LELCC) is a rare intrahepatic tumor. There are usually no specific physical findings, and the tumors are often diagnosed incidentally and are frequently large-sized at diagnosis. The imaging findings of LELCC resemble those of hepatocellular carcinoma (HCC). Tumors are often found in large-sized and advanced at diagnosis, and the main treatment of the disease is surgical resection. Herein, we report treating a patient with early stage LELCC by radiofrequency ablation (RFA). We diagnosed this tumor in a 27-year-old Chinese female with a history of chronic hepatitis B (CHB). Based on the findings of blood examination, abdominal ultrasonography, and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI), this tumor was diagnosed as suspected HCC. Ultrasound-guided percutaneous tumor biopsy and RFA were performed at the same time. The histopathological findings finally revealed the diagnosis of LELCC. To the best of our knowledge, this is the first report, in the English-language literature, of the treatment of LELCC by RFA; we suggest that RFA might be a candidate treatment for small-sized early stage LELCC.

DOI： 10.1007/s12328-020-01303-4

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INTRODUCTION: The treatment of diabetes has a significant impact on the pathogenesis of non-alcoholic fatty liver disease (NAFLD). We compared the effectiveness of tofogliflozin, a selective sodium-glucose cotransporter 2 inhibitor, and pioglitazone for the treatment of NAFLD patients with type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: This open-label, prospective, single-center, randomized clinical trial recruited NAFLD patients with type 2 diabetes mellitus and a hepatic fat fraction of at least 10% as assessed based on the MRI-proton density fat fraction (MRI-PDFF). Eligible patients were stratified according to hemoglobin A1c (HbA1c), alanine transaminase, and MRI-PDFF levels and randomly assigned (1:1) to receive either 20 mg tofogliflozin or 15-30 mg pioglitazone, orally, once daily for 24 weeks. The primary endpoint was an absolute change in MRI-PDFF at 24 weeks. Efficacy and safety was assessed in all treated patients. This trial was registered in the Japan Registry of Clinical Trials. RESULTS: Overall, 40 eligible patients were randomly assigned to receive tofogliflozin (n=21) or pioglitazone (n=19). Changes in hepatic steatosis after 24 weeks of treatment were evaluated by MRI-PDFF, which showed a significant decrease in both groups (-7.54% (p<0.0001) and -4.12% (p=0.0042) in the pioglitazone and tofogliflozin groups, respectively). Compared with baseline, the body weight decreased by 2.83±2.86 kg (-3.6%, p=0.0443) in the tofogliflozin group and increased by 1.39±2.62 kg (1.7%, p=0.0002) in the pioglitazone group after 24 weeks. No life-threatening events or treatment-related deaths occurred. CONCLUSIONS: Tofogliflozin was well tolerated, and it reduced the MRI-PDFF levels in NAFLD patients with type 2 diabetes mellitus. TRIAL REGISTRATION NUMBER: jRCTs031180159.

DOI： 10.1136/bmjdrc-2020-001990

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Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. It occurs with a prevalence of up to 25%, of which 10-20% cases progress to nonalcoholic steatohepatitis (NASH), cirrhosis, and liver cancer. The histopathology of NASH is characterized by neutrophilic infiltration, and endotoxins from gram-negative rods have been postulated as a contributing factor. Elevations in endotoxin levels in the blood can be classified as intestinal and hepatic factors. In recent years, leaky gut syndrome, which is characterized by impaired intestinal barrier function, has become a significant issue. A leaky gut may prompt intestinal bacteria dysbiosis and increase the amount of endotoxin that enters the liver from the portal vein. These contribute to persistent chronic inflammation and progressive liver damage. In addition, hepatic factors suggest that liver damage can be induced by low-dose endotoxins, which does not occur in healthy individuals. In particular, increased expression of CD14, an endotoxin co-receptor in the liver, may result in leptin-induced endotoxin hyper-responsiveness in obese individuals. Thus, elevated blood endotoxin levels contribute to the progression of NASH. The current therapeutic targets for NASH treat steatosis and liver inflammation and fibrosis. While many clinical trials are underway, no studies have been performed on therapeutic agents that target the intestinal barrier. Recently, a randomized placebo-controlled trial examined the role of the intestinal barrier in patients with NAFLD. To our knowledge, this study was the first of its kind and study suggested that the intestinal barrier may be a novel target in the future treatment of NAFLD.

DOI： 10.3389/fendo.2021.770986

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Non-alcoholic fatty liver disease (NAFLD) is now recognized as the most common chronic liver disease worldwide, along with the concurrent epidemics of metabolic syndrome and obesity. Patients with NAFLD have increased risks of end-stage liver disease, hepatocellular carcinoma, and liver-related mortality. However, the largest cause of death among patients with NAFLD is cardiovascular disease followed by extrahepatic malignancies, whereas liver-related mortality is only the third cause of death. Extrahepatic complications of NAFLD include chronic kidney disease, extrahepatic malignancies (such as colorectal cancer), psychological dysfunction, gastroesophageal reflux disease, obstructive sleep apnea syndrome, periodontitis, hypothyroidism, growth hormone deficiency, and polycystic ovarian syndrome. The objective of this narrative review was to summarize recent evidences about extrahepatic complications of NAFLD, with focus on the prevalent/incident risk of such diseases in patients with NAFLD. To date, an appropriate screening method for extrahepatic complications has not yet been determined. Collaborative care with respective experts seems to be necessary for patient management because extrahepatic complications can occur across multiple organs. Further studies are needed to reveal risk profiles at baseline and to determine an appropriate screening method for extrahepatic diseases.

DOI： 10.3390/diagnostics10110912

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The prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) has increased rapidly worldwide, making NAFLD/NASH an important global health problem from both a medical and socioeconomic standpoint. NAFLD is also regarded as a liver component of metabolic syndrome and is reported to be associated with the risk factors for metabolic syndrome. It has been suggested that NAFLD/NASH be recognized both as a liver-specific disease and as an early mediator of systemic diseases. Liver biopsy is recommended as the gold standard method for the diagnosis of NASH and for the staging of liver fibrosis in patients with NAFLD. However, because of its high cost, high risk, and high weightage as a healthcare resource, invasive liver biopsy is a poorly suited diagnostic test for such a highly prevalent condition. Therefore, the development of reliable noninvasive methods for the assessment of liver fibrosis has been sought to estimate the risk of progression of NASH to cirrhosis, estimate the risk of cardiovascular events, aid in the surveillance for HCC, and guide therapy in patients with NAFLD/NASH. In this review, we highlight the principles and recent advances in ultrasound elastography techniques (Real-time Tissue Elastography®, vibration-controlled transient elastography, point shear wave elastography, and two-dimensional shear wave elastography) used to evaluate the liver fibrosis stage and steatosis grade in patients with NAFLD.

DOI： 10.1007/s10396-020-01040-8

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AIM: Although liver biopsy is the gold standard for the diagnosis and staging of non-alcoholic fatty liver disease (NAFLD), repeated assessment of patients' liver tissue conditions are impractical. We assessed the 10-year changes in liver stiffness measurements (LSM) utilizing vibration-controlled transient elastography in NAFLD patients. METHODS: From January 2006 to September 2007, LSM was carried out for 97 biopsy-proven NAFLD patients. Of these, 34 patients underwent 10-year LSM reassessments (14 of them with paired biopsies). RESULTS: We evaluated the changes in the fibrosis stage as estimated using LSM (FS-LSM). Over a 10-year period, 32.4% had FS-LSM progression, 50% had static disease, and 17.6% had FS-LSM improvement. From among the initially diagnosed non-alcoholic steatohepatitis patients, 18% had progressed to considerable stage 4 (cirrhosis) 10 years later. In this cohort, none of the patients who had been initially diagnosed as FS-LSM stage 0 had progressed to cirrhosis 10 years later. The changes in LSM were correlated with the change in the histological fibrosis stage, the NAFLD activity score, and the change in the sum of the steatosis, activity, and fibrosis score. Improving more than 1 body mass index (kg/m2 ) and having a higher initial aspartate aminotransferase, alanine aminotransferase (ALT), or ALT responder (>30% improvement or reduction to less than 40 IU/L) were factors contributing to LSM improvements (≥2 kPa). CONCLUSIONS: Vibration-controlled transient elastography is likely to become a more clinically important tool for the long-term monitoring of NAFLD patients.

DOI： 10.1111/hepr.13349

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(株)日本メディカルセンター  

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Language：Japanese   Publisher：(株)日本メディカルセンター  

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Language：Japanese   Publisher：(NPO)日本歯周病学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(NPO)日本歯周病学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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Language：Japanese   Publisher：日本消化器病学会-関東支部  

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Language：Japanese   Publisher：(株)診断と治療社  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J00697&link_issn=&doc_id=20231218110014&doc_link_id=10.34433%2Fdt.0000000514&url=https%3A%2F%2Fdoi.org%2F10.34433%2Fdt.0000000514&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Language：Japanese   Publisher：日本消化器病学会-関東支部  

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Language：Japanese   Publisher：(株)アークメディア  

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Language：Japanese   Publisher：(株)診断と治療社  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J00697&link_issn=&doc_id=20231218110014&doc_link_id=10.34433%2Fdt.0000000514&url=https%3A%2F%2Fdoi.org%2F10.34433%2Fdt.0000000514&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(有)科学評論社  

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Language：Japanese   Publisher：産業開発機構(株)  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J00116&link_issn=&doc_id=20230519190009&doc_link_id=%2Fan7eizoc%2F2023%2F005506%2F011%2F0056-0061%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fan7eizoc%2F2023%2F005506%2F011%2F0056-0061%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：産業開発機構(株)  

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Language：Japanese   Publisher：(公社)日本超音波医学会  

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Language：Japanese   Publisher：(公社)日本超音波医学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(公社)日本超音波医学会  

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Language：Japanese   Publisher：(公社)日本超音波医学会  

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Language：Japanese   Publisher：(NPO)日本高齢消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：日本消化器病学会-関東支部  

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Language：Japanese   Publisher：(一社)日本集中治療医学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(有)科学評論社  

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Language：Japanese   Publisher：(公社)日本超音波医学会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J00833&link_issn=&doc_id=20220921440003&doc_link_id=%2Fed5choon%2F2022%2F004905%2F005%2F0397-0410%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fed5choon%2F2022%2F004905%2F005%2F0397-0410%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(NPO)日本歯周病学会  

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Language：Japanese   Publisher：(NPO)日本高齢消化器病学会  

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：Japanese   Publisher：(有)科学評論社  

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Language：Japanese   Publisher：(公社)日本超音波医学会  

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Language：Japanese   Publisher：日本消化器病学会-関東支部  

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Language：Japanese   Publisher：梵天書房  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：医学図書出版(株)  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J06599&link_issn=&doc_id=20211101360016&doc_link_id=%2Faa6kancd%2F2021%2F000701%2F017%2F0096-0100%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faa6kancd%2F2021%2F000701%2F017%2F0096-0100%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：日本消化器病学会-関東支部  

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Language：Japanese   Publisher：(有)科学評論社  

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Language：Japanese   Publisher：(一社)日本言語聴覚士協会  

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Language：Japanese   Publisher：(株)日本メディカルセンター  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：日本消化器病学会-関東支部  

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Language：Japanese   Publisher：(株)日本臨床社  

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Language：Japanese   Publisher：(公財)腸内細菌学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：Japanese   Publisher：医学図書出版(株)  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J00001&link_issn=&doc_id=20200824440007&doc_link_id=%2Faa6icutc%2F2020%2F004407%2F008%2F0445-0452%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faa6icutc%2F2020%2F004407%2F008%2F0445-0452%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(有)科学評論社  

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Language：Japanese   Publisher：日本消化器病学会-関東支部  

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Language：Japanese   Publisher：日本消化器病学会-関東支部  

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Language：Japanese   Publisher：日本消化器病学会-関東支部  

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Language：Japanese   Publisher：日本大学医学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(株)響文社  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：日本内科学会-関東地方会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(株)アークメディア  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(NPO)日本消化吸収学会  

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Language：Japanese   Publisher：(NPO)日本高齢消化器病学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J00192&link_issn=&doc_id=20170713310006&doc_link_id=10.11280%2Fgee.59.1329&url=https%3A%2F%2Fdoi.org%2F10.11280%2Fgee.59.1329&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：神奈川県医師会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J04450&link_issn=&doc_id=20170112130046&doc_link_id=10.11641%2Fpde.89.1_144&url=https%3A%2F%2Fdoi.org%2F10.11641%2Fpde.89.1_144&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(NPO)日本消化吸収学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(NPO)日本消化吸収学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：神奈川県医師会  

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Language：Japanese   Publisher：神奈川県医師会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(NPO)日本消化吸収学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：神奈川県医師会  

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Language：Japanese   Publisher：広島市立広島市民病院  

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Language：Japanese   Publisher：広島医学会  

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Language：Japanese   Publisher：(一社)日本組織適合性学会  

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Event date： 2024.6

Presentation type：Symposium, workshop panel (public)  

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Event date： 2024.6

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2024.6

Presentation type：Symposium, workshop panel (public)  

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Event date： 2024.6

Language：English   Presentation type：Poster presentation  

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Event date： 2024.3

Language：English   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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Event date： 2023.12

Presentation type：Symposium, workshop panel (public)  

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Event date： 2023.6

Presentation type：Symposium, workshop panel (public)  

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Event date： 2023.5

Presentation type：Symposium, workshop panel (nominated)  

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Event date： 2023.4

Presentation type：Symposium, workshop panel (public)  

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Event date： 2023.2

Language：English   Presentation type：Oral presentation (general)  

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Event date： 2022.11

Presentation type：Oral presentation (general)  

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Event date： 2022.11

Language：English   Presentation type：Poster presentation  

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Event date： 2022.6

Presentation type：Symposium, workshop panel (public)  

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Event date： 2021.8

Language：English   Presentation type：Poster presentation  

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Event date： 2021.6

Presentation type：Symposium, workshop panel (public)  

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Event date： 2019.12

Presentation type：Oral presentation (general)  

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Event date： 2018.4

Presentation type：Poster presentation  

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Event date： 2017.11 - 2017.12

Presentation type：Symposium, workshop panel (public)  

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Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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Presentation type：Poster presentation  

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Presentation type：Oral presentation (general)  

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Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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Presentation type：Symposium, workshop panel (nominated)  

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Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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Presentation type：Oral presentation (general)  

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Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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