Prevalence and associated metabolic factors of nonalcoholic fatty liver disease in the general population from 2014 to 2018 in Japan: A large-scale multicenter retrospective study.

AIM: The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. The aim of this study was to determine the recent prevalence and clinical characteristics of NAFLD in Japan. METHODS: This study initially included 410 061 retrospectively enrolled adults from the medical health checkup registry for metabolic syndrome, chronic kidney disease, and fatty liver in Japan (MIRACLE-J; UMIN-CTR no. UMIN000049419), who were evaluated between 2014 and 2018 at 13 health centers in Japan. Individuals consuming >20 g of alcohol/day or with chronic liver disease were excluded. Fatty liver was diagnosed by ultrasonography. The probability of NAFLD with advanced fibrosis was estimated based on the fibrosis-4 index and NAFLD fibrosis score. RESULTS: A total of 71 254 participants were included in the final analysis. The overall prevalence of NAFLD was 25.8%. There was a significant, twofold difference in NAFLD prevalence between men (37.4%) and women (18.1%). Nonalcoholic fatty liver disease prevalence increased linearly with body mass index, triglycerides, and low-density lipoprotein cholesterol regardless of threshold values, even in the absence of obesity. Among patients with NAFLD, 14% had diabetes mellitus, 31% had hypertension, and 48% had dyslipidemia. The estimated prevalence of NAFLD with advanced fibrosis was 1.7% and 1.0% according to the fibrosis-4 index and NAFLD fibrosis score, respectively. CONCLUSIONS: The prevalence of NAFLD was approximately one-quarter of the general population in Japan. There was a linear relationship between NAFLD prevalence and various metabolic parameters, even in nonobese participants. The prevalence of NAFLD with advanced fibrosis was estimated to be 1%-2%.

Impact of body size on first-line Helicobacter pylori eradication success using vonoprazan and amoxicillin dual therapy.

BACKGROUND: As a first-line therapy for Helicobacter pylori, dual therapy with vonoprazan and amoxicillin (VA-dual) provides an eradication rate similar to that of vonoprazan-based triple therapy. As the factors associated with the eradication rate of H. pylori with VA-dual are unknown,we investigated them in this study. MATERIALS AND METHODS: Overall, 163 patients diagnosed with H. pylori infection received VA-dual (vonoprazan 20 mg twice daily and amoxicillin 750 mg twice daily for 7 d). The association between successful H. pylori eradication and the following patient clinical factors was analyzed: sex, age, height, weight, body surface area (BSA), body mass index (BMI), history of early gastric carcinoma and peptic ulcer, comorbidity of cirrhosis, alcohol consumption habit, smoking habit, common use of proton pump inhibitors, and concomitant use of drugs that are substratesof cytochrome P450 (CYP) 3A4. The association between post-eradication adverse events and clinical factors was analyzed retrospectively. RESULTS: Successful H. pylori eradication was associated with a lower BSA (eradication rate: 90.8% in patients with BSA <1.723 vs. 79.6% in those with BSA ≥1.723; p = 0.045). The incidence of adverse events was higher in women than in men (adverse events: 40.0% in women vs. 19.4% in men; p = 0.004). CONCLUSIONS: Successful H. pylori eradication with VA-dual was associated with the small body size of patients. This therapy may have to be adjusted per body size.

High Body Mass Index Is Correlated with the Success of Vonoprazan-Based Second-Line Therapy for Helicobacter Pylori Infection.

Eradication of Helicobacter pylori (Hp) is necessary for preventing peptic ulcers and stomach cancer. The potassium-competitive acid blocker vonoprazan is a gastric acid secretion inhibitor that improves the success rate of Hp eradication through its immediate and persistent inhibition of acid excretion. In Japan, first-line treatment involves a regimen in which vonoprazan is combined with amoxicillin and clarithromycin, while second-line treatment involves vonoprazan combined with amoxicillin and metronidazole. However, in contrast to the vonoprazan-based first-line therapy, no studies have investigated the factors influencing the success of vonoprazan-based second-line therapy. In this study, we therefore aimed to investigate factors related to the success of vonoprazan-based second-line therapy. We analyzed the association between the success of Hp eradication and patient factors including metronidazole/amoxicillin minimal inhibitory concentrations (MICs). MICs were measured using the Hp isolated from each patient. A receiver operating characteristic (ROC) analysis was conducted to examine continuous variables and eradication success. We reviewed the records of 33 patients (age: 34-79 years, male/female: 22/11, and body mass index (BMI): 16.1-28.8 kg/m2) who underwent vonoprazan-based second-line therapy after failure of first-line therapy at seven Japanese facilities between October 2018 and June 2019. The eradication success rate was 81.8% (27/33). ROC analysis revealed an area under the curve and BMI cutoff value of 0.796 and 23.8 kg/m2, respectively. The eradication success rate was higher in patients with high BMI than in those with low BMI (p = 0.007). Our findings indicate that higher BMI is correlated with the success of vonoprazan-based second-line therapy.

[Infection status of Helicobacter pylori with antibody values of 3.0U/mL or more and less than 10.0U/mL in the LZ test "Eiken" H. pylori antibody].

The LZ test "Eiken" for H. pylori antibody (LZ test) was examined. In patients with an antibody titer of ≥3.0U/mL and <10.0U/mL among 698 patients who underwent breath tests, the status of H. pylori infection was assessed from the results of the 13C urea breath test and the findings of gastric mucosal atrophy by performing an upper gastrointestinal endoscopy. A positive 13C urea breath test was observed in 22.3% of these patients (156/698, 95% confidence interval 19.4-25.6%), and gastric mucosal atrophy of C-2 or greater was observed in 39.7%. We presumed that 156 (22.3%) patients had present H. pylori infections, 141 (20.2%) patients had experienced a previous infection, and 401 (57.5%) patients were uninfected. The infection rate of H. pylori (current infection+previous infection) was treated as a so-called "risk of gastric cancer" and was 42.6% (297/698, 95% confidence interval 38.9-46.3%). In the LZ test, the concept of a negative high value should be understood. A receiver operating characteristic curve plotted depending on whether the 13C urea breath test was positive or not gave a positive cutoff value of 5.6U/mL;values greater than the cutoff value were taken as indicative of the need to investigate the status of H. pylori infection. Even without gastric mucosal atrophy, 2.0% of these patients had a positive breath test. For gastritis localized in the antrum (C-1), 17.8% of the patients had positive breath test results.

Do body mass index trajectories affect the risk of type 2 diabetes? A case-control study.

BACKGROUND: Although obesity is a well-studied risk factor for diabetes, there remains an interest in whether "increasing body mass index (BMI)," "high BMI per se," or both are the actual risk factors for diabetes. The present study aimed to retrospectively compare BMI trajectories of individuals with and without diabetes in a case-control design and to assess whether increasing BMI alone would be a risk factor. METHODS: Using comprehensive health check-up data measured over ten years, we conducted a case-control study and graphically drew the trajectories of BMIs among diabetic patients and healthy subjects, based on coefficients in fitted linear mixed-effects models. Patient group was matched with healthy control group at the onset of diabetes with an optimal matching method in a 1:10 ratio. Simple fixed-effects models assessed the differences in increasing BMIs over 10 years between patient and control groups. RESULTS: At the time of matching, the mean ages in male patients and controls were 59.3 years [standard deviation (SD) = 9.2] and 57.7 years (SD = 11.2), whereas the mean BMIs were 25.0 kg/m(2) (SD = 3.1) and 25.2 kg/m(2) (SD = 2.9), respectively. In female patients and controls, the mean ages were 61.4 years (SD = 7.9) and 60.1 years (SD = 9.6), whereas the mean BMIs were 24.8 kg/m(2) (SD = 3.5) and 24.9 kg/m(2) (SD = 3.4), respectively. The simple fixed-effects models detected no statistical significance for the differences of increasing BMIs between patient and control groups in males (P = 0.19) and females (P = 0.67). Sudden increases in BMI were observed in both male and female patients when compared with BMIs 1 year prior to diabetes onset. CONCLUSIONS: The present study suggested that the pace of increasing BMIs is similar between Japanese diabetic patients and healthy individuals. The increasing BMI was not detected to independently affect the onset of type 2 diabetes.

A Simple Clinical Scoring System to Determine the Risk of Pancreatic Cancer in the General Population.

This study aimed to develop and validate a simple scoring system to determine the high-risk group for pancreatic cancer (PC) in the asymptomatic general population. The scoring system was developed using data from PC cases and randomly selected non-PC cases undergoing annual medical checkups between 2008 and 2013. The performance of this score was validated for participants with medical checkups between 2014 and 2016. In the development set, 45 PC cases were diagnosed and 450 non-PC cases were identified. Multivariate analysis showed three changes in clinical data from 1 year before diagnosis as independent risk factors: ΔHbA1c ≥ 0.3%, ΔBMI ≤ -0.5, and ΔLDL ≤ -20 mg/dL. A simple scoring system, incorporating variables and abdominal ultrasound findings, was developed. In the validation set, 36 PC cases were diagnosed over a 3-year period from 32,877 participants. The AUROC curve of the scoring system was 0.925 (95%CI 0.877-0.973). The positive score of early-stage PC cases, including Stage 0 and I cases, was significantly higher than that of non-PC cases (80% vs. 6%, p = 0.001). The simple scoring system effectively narrows down high-risk PC cases in the general population and provides a reasonable approach for early detection of PC.

Effectiveness of screening endoscopy for esophageal squamous cell carcinoma in Japanese males.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) has a poor prognosis; therefore, early detection is essential. In Japan, more than 90% of esophageal cancers are ESCC. Endoscopy is effective to detect ESCC in the early stage, but there is a limited number of reports examining its efficacy and effectiveness. OBJECTIVE: This study aimed to evaluate the efficacy of screening endoscopy for detecting ESCC. METHODS: This retrospective study analyzed the prevalence of ESCC, annual transition of prevalence, and the stage of each ESCC among 128,520 medical check-up patients who underwent esophagogastroduodenoscopy from April 2015 to March 2020 at Yamanashi Koseiren Health Care Center. Furthermore, a case-control study utilized the multivariate logistic regression analysis was performed to assess the risk factor of ESCC. RESULTS: Among a total of 128,520 subjects, 42 ESCC patients were detected, with 95.2% being diagnosed at early stages. Annual prevalence in males was 0.015% (2/13,122) in 2015, 0.044% (6/13,562) in 2016, 0.044% (6/13,676) in 2017, 0.074% (10/13,488) in 2018%, and 0.11% (16/14,386) in 2019. ESCC prevalence has been increasing each year. A significant increase was observed between 2015 and 2018 (p = 0.039). ESCC prevalence was 0.102% (25/24,272) when focusing on males aged over 50 years with a history of smoking and drinking. Regarding the case-control study, the multivariate logistic regression analysis revealed smoking (p = 0.044), mean corpuscular volume (MCV) (p = 0.0018), and severe gastric atrophy (p = 0.048) as positively correlated with ESCC. CONCLUSION: In conclusion, ESCC has been increasing in our center from 2015 to 2019, and the prevalence has been approaching that of gastric cancer in 2019 in male subjects. ESCC can be detected efficiently by targeting males with high MCV who have a history of drinking and smoking.

Random forest approach for determining risk prediction and predictive factors of type 2 diabetes: large-scale health check-up data in Japan.

INTRODUCTION: Early intervention in type 2 diabetes can prevent exacerbation of insulin resistance. More effective interventions can be implemented by early and precise prediction of the change in glycated haemoglobin A1c (HbA1c). Artificial intelligence (AI), which has been introduced into various medical fields, may be useful in predicting changes in HbA1c. However, the inability to explain the predictive factors has been a problem in the use of deep learning, the leading AI technology. Therefore, we applied a highly interpretable AI method, random forest (RF), to large-scale health check-up data and examined whether there was an advantage over a conventional prediction model. RESEARCH DESIGN AND METHODS: This study included a cumulative total of 42 908 subjects not receiving treatment for diabetes with an HbA1c <6.5%. The objective variable was the change in HbA1c in the next year. Each prediction model was created with 51 health-check items and part of their change values from the previous year. We used two analytical methods to compare the predictive powers: RF as a new model and multivariate logistic regression (MLR) as a conventional model. We also created models excluding the change values to determine whether it positively affected the predictions. In addition, variable importance was calculated in the RF analysis, and standard regression coefficients were calculated in the MLR analysis to identify the predictors. RESULTS: The RF model showed a higher predictive power for the change in HbA1c than MLR in all models. The RF model including change values showed the highest predictive power. In the RF prediction model, HbA1c, fasting blood glucose, body weight, alkaline phosphatase and platelet count were factors with high predictive power. CONCLUSIONS: Correct use of the RF method may enable highly accurate risk prediction for the change in HbA1c and may allow the identification of new diabetes risk predictors.

Evaluation of deep convolutional neural networks for glaucoma detection.

PURPOSE: To investigate the performance of deep convolutional neural networks (DCNNs) for glaucoma discrimination using color fundus images STUDY DESIGN: A retrospective study PATIENTS AND METHODS: To investigate the discriminative ability of 3 DCNNs, we used a total of 3312 images consisting of 369 images from glaucoma-confirmed eyes, 256 images from glaucoma-suspected eyes diagnosed by a glaucoma expert, and 2687 images judged to be nonglaucomatous eyes by a glaucoma expert. We also investigated the effects of image size on the discriminative ability and heatmap analysis to determine which parts of the image contribute to the discrimination. Additionally, we used 465 poor-quality images to investigate the effect of poor image quality on the discriminative ability. RESULTS: Three DCNNs showed areas under the curve (AUCs) of 0.9 or more. The AUC of the DCNN using glaucoma-confirmed eyes against nonglaucomatous eyes was higher than that using glaucoma-suspected eyes against nonglaucomatous eyes by approximately 0.1. The image size did not affect the discriminative ability. Heatmap analysis showed that the optic disc area was the most important area for the discrimination of glaucoma. The image quality affected the discriminative ability, and the inclusion of poor-quality images in the analysis reduced the AUC by 0.1 to 0.2. CONCLUSIONS: DCNNs may be a useful tool for detecting glaucoma or glaucoma-suspected eyes by use of fundus color images. Proper preprocessing and collection of qualified images are essential to improving the discriminative ability.

Weight cycling and the subsequent onset of type 2 diabetes mellitus: 10-year cohort studies in urban and rural Japan.

OBJECTIVE: To investigate how weight cycling (gaining and losing weight) affects the risk of diabetes. DESIGN: Cohort studies. SETTING: Primary healthcare in urban and rural Japan. PARTICIPANTS: 20 708 urban and 9670 rural residents. PRIMARY OUTCOME MEASURES: ORs for diabetes in those with weight loss, weight loss-gain, stable weight, weight gain-loss and weight gain over 10 years. Weight gain and loss were defined as a change of more than ±4% from baseline weight. RESULTS: In the urban region, the ORs relative to the stable group for the loss-gain and gain-loss groups were 0.63 (95% CI 0.45 to 0.89) and 0.51 (95% CI 0.32 to 0.82) for men and 0.72 (95% CI 0.39 to 1.34) and 1.05 (95% CI 0.57 to 1.95) for women. In the rural region, they were 1.58 (95% CI 0.78 to 3.17) and 0.44 (95% CI 0.15 to 1.29) in men and 0.41 (95% CI 0.12 to 1.44) and 0.77 (95% CI 0.28 to 2.14) in women. The ORs for an increase in weight between 5 and 10 kg from the age of 20 years were 1.54 (95% CI 1.03 to 2.30) in men and 0.96 (95% CI 0.55 to 1.65) in women. CONCLUSIONS: In Japan, weight cycling was associated with a significant reduction in the risk of diabetes for men from urban regions. The associations were unclear for women from urban regions and both men and women from rural regions. These results differ from those in Western studies, probably because of differences in diet, insulin secretion and sensitivity and weight-consciousness.

Evaluation of the associations between changes in intraocular pressure and metabolic syndrome parameters: a retrospective cohort study in Japan.

OBJECTIVE: The contributions of highly correlated cardiovascular risk factors to intraocular pressure (IOP) are not clear due to underlying confounding problems. The present study aimed to determine which metabolic syndrome parameters contribute to elevating IOP and to what extent. DESIGN: Retrospective cohort study. SETTING: A private healthcare centre in Japan. PARTICIPANTS: Individuals who visited a private healthcare centre and underwent comprehensive medical check-ups between April 1999 and March 2009 were included (20,007 in the cross-sectional study and 15,747 in the longitudinal study). PRIMARY AND SECONDARY OUTCOME MEASURES: Changes in IOP were evaluated in terms of ageing and changes in metabolic syndrome parameters. Pearson's correlation coefficients and mixed-effects models were used to examine the relationship of changes in IOP with ageing and changes in metabolic syndrome parameters in cross-sectional and longitudinal studies, respectively. RESULTS: In the cross-sectional study, IOP was negatively correlated with age and positively correlated with waist circumference, high-density lipoprotein cholesterol (HDL-C) levels, triglyceride levels, systolic blood pressure (SBP), diastolic blood pressure (DBP) and fasting plasma glucose (FPG) levels. In the longitudinal multivariate analysis, the associated IOP changes were -0.12 (p<0.0001) mm Hg with male sex; -0.59 (p<0.0001) mm Hg with 10 years of ageing; +0.42 (p<0.0001) mm Hg with 1 mmol/L increase in HDL-C levels; +0.092 (p<0.0001) mm Hg with 1 mmol/L increase in triglyceride levels; +0.090 (p<0.0001) mm Hg with 10 mm Hg increase in SBP; +0.085 (p<0.0001) mm Hg with 10 mm Hg increase in DBP; and+0.091 (p<0.0001) mm Hg with 1 mmol/L increase in FPG levels. CONCLUSIONS: Elevation of IOP was related to longitudinal worsening of serum triglyceride levels, blood pressure and FPG and improvement in serum HDL-C levels.

The relationship between gallbladder disease and smoking and drinking habits in middle-aged Japanese.

BACKGROUND: Few studies have investigated the association between smoking and ultrasonographically diagnosed gallbladder (GB) disease, and their results were uncertain. This study was conducted to examine the association between smoking and drinking and GB diseases. METHODS: A total of 9,947 subjects (age, 30-69 years; 4,953 men and 4,994 women) voluntarily received a paid medical check-up at our center in Yamanashi Prefecture in Japan. All of the subjects underwent abdominal ultrasonographic (US) examination, a demographic check, and a biochemical test, and answered a self-administered questionnaire asking about smoking habits and alcohol consumption. Of the 9,947 subjects, 483 had gallstones, 819 had gallbladder polyps, and 169 were in a state of postcholecystectomy. We compared the findings in this group with the findings in 8,417 people (4,144 males and 4,273 females) with normal gallbladder. RESULTS: Multiple regression analysis among males showed that cigarette smoking was inversely related to GB polyps (odds ratio, [OR], 0.76; 95% confidence internal [CI], 0.59-0.98 and OR, 0.74; 95% CI, 0.56-0.98, respectively, for current and ex-smokers). Ex-smokers a showed positive association with the postcholecystectomy state (OR, 2.56; 95% CI, 1.18-5.52). Light drinkers showed an inverse relation to GB stones (OR, 0.69; 95% CI, 0.49-0.99), and heavy drinkers showed an inverse relation to GB polyps (OR, 0.68; 95% CI, 0.51-0.90). Current drinkers showed an inverse relation to the postcholecystectomy state (OR, 0.48; 95% CI, 0.28-0.83). CONCLUSIONS: Cigarette smoking was inversely related to gallbladder polyps in males and was positively related to the postcholecystectomy state. Drinking was inversely related to gallstones, GB polyps, and the postcholecystectomy state in males.

The association of fatty liver and diabetes risk.

We examined whether fatty liver, as diagnosed with abdominal ultrasonography, is an independent risk factor for diabetes mellitus during 10 years of follow-up. A total of 840 subjects (467 men and 373 women) were followed for the entire 10 years. The criteria for being non-diabetic were having no history of diabetes, having a fasting plasma glucose level of less than 110 mg/dl and a serum hemoglobin A1c level of 6.4% or less. We indicated that every examine received all examinations after 12 hours of fasting. Well-trained technicians performed abdominal ultrasonography. Although univariate analysis revealed that the presence of fatty liver was related to hyperglycemia 10 years later, multiple logistic regression analysis did not support this finding. In the multiple logistic regression analysis fasting plasma glucose levels at the baseline and age were significantly related to hyperglycemia (odds ratio [OR] = 1.16, 95% confidence interval [CI]: 1.11-1.21, OR = 1.07, 95% CI: 1.01-1.14, respectively). Fatty liver was not an independent risk factor for hyperglycemia in our follow-up study 10 years after the first diagnosis. The high fasting plasma glucose levels were a risk factor for diabetes, even in the normal range.