Impact of Body Weight Gain on the Incidence of Nonalcoholic Fatty Liver Disease in Nonobese Japanese Individuals.

INTRODUCTION: We aimed to investigate the effect of recent short-term weight gain on the incidence of nonalcoholic fatty liver disease (NAFLD) in nonobese (body mass index < 25 kg/m) participants. METHODS: This retrospective cohort study included nonobese individuals who participated in an annual health checkup between 2008 and 2018 in Tokyo, Japan. We estimated the multivariable adjusted hazard ratio for the development of NAFLD diagnosed via ultrasound after a 3-kg unit gain in weight measured at a 2-year landmark time point postbaseline. Multivariable adjustments included weight change from the age of 20 and other relevant confounding factors. Sensitivity analyses using additional landmark time points at 1, 3, 4, and 5 years postbaseline and time-dependent Cox proportional hazards regressions were performed. RESULTS: Among the 27,064 nonobese participants (142,699 person years of follow-up), 2,895 were diagnosed with NAFLD. Approximately 90% of the patients with NAFLD maintained their nonobese status before disease diagnosis. The adjusted hazard ratio for the development of NAFLD (for a 3-kg unit of weight gain) at the 2-year landmark time point postbaseline was 1.60 (95% confidence interval, 1.46-1.76) in nonobese men and 1.66 (95% confidence interval, 1.51-1.83) in nonobese women. This association was maintained in the sensitivity analyses. DISCUSSION: Recent short-term weight gain is an independent risk factor for NAFLD development in nonobese men and women. Clinicians should be mindful of the association between weight gain and NAFLD onset, even in the nonobese population.

Noneffectiveness of scopolamine for facilitating detection of upper gastrointestinal neoplasia during screening esophagogastroduodenoscopy: propensity score-matched study.

BACKGROUND: Antispasmodics, such as scopolamine, are widely used in several countries prior to diagnostic and screening esophagogastroduodenoscopy (EGD), with the goal of optimizing the detection of minute lesions, typically early gastric cancer (T1 lesions). The aim of this study was to determine whether scopolamine facilitates detection of gastric cancer in the screening setting. METHODS: A propensity score-matched retrospective study was conducted in a tertiary referral medical center in Tokyo, Japan. Consecutive individuals (n = 40 776) underwent screening EGD between January 2011 and May 2016. All outcome lesions were diagnosed with histopathological confirmation. Detection of esophageal cancer, gastric adenoma, duodenal adenoma, and upper gastrointestinal neoplasia (UGIN) were investigated as secondary outcomes. RESULTS: Scopolamine was used in 31 130 patients (76.3 %) and propensity score matching yielded 6625 pairs. Bivariate analysis revealed no significant association between possible confounders (age, sex, overweight, atrophic gastritis, alcohol history, smoking history, midazolam use, endoscopist biopsy rate grade, and gastric cancer in first-degree relatives) and scopolamine use. Lesions detected were 18 gastric cancers, 11 esophageal cancers, 19 gastric adenomas, 6 duodenal adenomas, and 54 UGINs, with no significant association between scopolamine use and lesion detection. CONCLUSIONS: Scopolamine use did not appear to effectively facilitate detection of gastric or esophageal cancer, gastric or duodenal adenoma, and UGIN during screening EGD. Scopolamine should be avoided until its efficacy is confirmed by a randomized controlled trial.

The relationship between preference-based health-related quality of life and lifestyle behavior: a cross-sectional study on a community sample of adults who had undergone a health check-up.

BACKGROUND: Preference-based Health-Related Quality of Life (HRQL) is one of the most important indicators for calculating QALY (Quality-Adjusted Life Years) in a cost-effectiveness analysis. This study aimed to collect data on healthy individuals' HRQL based on the preferences of Japanese people who had undergone a comprehensive health check-up, and to examine the influence of relevant factors, such as blood biochemical data and lifestyle behavior. METHODS: We conducted a cross-sectional study targeting people who had undergone a comprehensive health check-up in 2015. Participants were asked to respond to a medical interview sheet. We then examined the utility value, as well as lifestyle habits such as alcohol intake, smoking, and exercise. HRQL was examined using EQ-5D-5L. Using a multiple regression analysis, we examined the influence of related factors, such as lifestyle and biochemical test data. RESULTS: We collected 2037 responses (mean age = 54.98 years; 55.0% female). The average preference-based health-related HRQL was 0.936 ± 0.087. A total of 1167 people (57.2%) responded that they were completely healthy. The biochemical test data that were recognized to correlate with HRQL were hemoglobin, total cholesterol, creatinine, all of which were weak (r = - 0.045-0.113). The results of multiple regression analysis showed that significant facts were: being female, age (≧70 year-old), drinking alcohol (sometimes), activity (very often), and lack of sleep. CONCLUSIONS: The HRQL of participants who had undergone a comprehensive health check-up was generally high, and only declined for those over 70 years of age. It is suggested that preference-based HRQL is related to physical activity, and that decrease of activity and lack of sleep leads to a decrease in HRQL.

Association of weight gain since age 20 with non-alcoholic fatty liver disease in normal weight individuals.

BACKGROUND AND AIMS: Interventions for lifestyle diseases including non-alcoholic fatty liver disease (NAFLD) have focused on overweight and obese populations. The impact of adult weight gain on NAFLD development among normal weight individuals remains unclear. METHODS: In this cross-sectional study, we collected data from participants presenting to a health check-up program. Ultrasound-diagnosed NAFLD prevalence was examined over 1-kg increments of weight change since age 20. Relative risks were calculated in men and women stratified by current weight (normal, overweight, and obese). Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for potential confounders. RESULTS: Among 21 496 participants, 3498 cases of NAFLD (16.3%) were observed. Prevalence of NAFLD increased with weight gain since age 20; among the 10.1-11.0 kg weight gain group, 41.6% of men and 24.8% of women had NAFLD. Multivariate analysis by quartiles showed that weight change was significantly associated with NAFLD risk in men and women. Risk of NAFLD associated with weight change (10-kg increments) was significantly higher in normal weight individuals (men: OR 7.53, 95% CI: 4.99-11.36, women: OR 12.20, 95% CI: 7.45-19.98) than overweight (men: OR 1.61, 95% CI: 0.91-2.85, women: OR 2.90, 95% CI: 0.99-8.54) and obese (men: OR 4.0, 95% CI: 2.97-5.39, women: OR 2.68, 95% CI: 2.00-3.60). CONCLUSIONS: NAFLD is robustly associated with weight change since age 20. This effect appears particularly strong in individuals at normal weight, suggesting an important role for early and longitudinal weight monitoring, even among healthy individuals at normal weight.

Image-enhanced, chromo, and cap-assisted colonoscopy for improving adenoma/neoplasia detection rate: a systematic review and meta-analysis.

OBJECTIVE: The effectiveness of narrow band imaging (NBI), chromoendoscopy (CE), and cap-assisted colonoscopy (CAC) on adenoma detection rate (ADR) has been investigated in previous meta-analyses; however, there have been no meta-analyses of autofluorescence imaging (AFI) or flexible spectral imaging color enhancement (FICE) or i-scan. The aim of this study was to determine whether AFI and FICE/i-scan was more effective than standard/high-definition white light endoscopy to improve ADR and to update previous meta-analyses of NBI, CE, and CAC. DESIGN: A systematic review and meta-analysis was conducted. Four investigators selected appropriate randomized controlled trials (RCT) using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. All RCTs in which colonoscopy were performed with AFI, FICE, i-scan, NBI, CE, and CAC were included. The risk ratios (RRs) calculated from adenoma/neoplasia detection rate were used as the main outcome measurement. RESULTS: A total of 42 studies were included in the analysis. Pooled estimates of RR (95%confidence interval [CI]) using AFI, FICE/i-scan, NBI, CE, and CAC were 1.04 (95% CI: 0.87-1.24) (I² = 0%) (fixed effects model [FEM]); 1.09 (95% CI: 0.97-1.23) (I² = 5%) (FEM); 1.03 (95% CI: 0.96-1.11) (I² = 0%) (FEM); 1.36 (95% CI: 1.23-1.51) (I² = 16%) (FEM); and 1.03 (95% CI: 0.93-1.14) (I² = 48%) (random effects model [REM]), respectively. The pooled estimate of RR (95%CI) using indigo carmine in non-ulcerative colitis (UC) patients and methylene blue in UC patients was 1.33 (95% CI: 1.20-1.48) (I² = 14%) (FEM) and 2.39 (95% CI: 1.18-4.84) (I² = 0%) (FEM), respectively. CONCLUSION: In contrast to AFI, FICE/i-scan, NBI, and CAC, only CE improves ADR. CE with methylene blue, though not NBI, is effective for surveillance of neoplasia in chronic UC patients.

Long-term cumulative incidence of metachronous advanced colorectal neoplasia after colonoscopy and a novel risk factor: a cohort study.

BACKGROUND AND AIM: Long-term cumulative incidence of and risk factors for metachronous advanced colorectal neoplasia, including both advanced colorectal adenoma (≥10 mm, or with villous or high-grade dysplasia) and colorectal cancer, are critical for surveillance strategies. The aim of this study was to determine the cumulative incidence of metachronous advanced colorectal neoplasia and its risk factors. METHODS: A retrospective cohort study was conducted on 6720 consecutive individuals who underwent general health check-ups and colonoscopy. Colorectal adenomas at initial colonoscopy were categorized as low-risk (1-2 small [<10 mm] tubular adenomas) or high-risk adenoma (≥3 tubular adenomas of any size; at least one adenoma ≥10 mm; or villous adenoma or adenoma with high-grade dysplasia). Kaplan-Meier estimates and hazard ratio by Cox-proportional hazard regression were calculated. RESULTS: The cumulative incidence (95% confidence interval [CI]) of metachronous advanced colorectal neoplasia at 5 and 10 years was 5.7% [4.6-7.1], and 11% [8.9-14] in the low-risk adenoma group, and 10% [8.6-13], and 17% [14-21] in high-risk adenoma group, respectively. Adjusted hazard ratio [95% CI] of low-risk adenoma (vs. no colorectal adenoma), high-risk adenoma (vs. no colorectal adenoma), current smoking and positive fecal immunochemical test were 1.34 [1.04-1.74], 1.94 [1.48-2.55], 1.55 [1.2-2.02] and 1.69 [1.35-2.1], respectively. Adjusted hazard ratio [95% CI] of positive fecal immunochemical test was 1.88 [1.29-2.74] in those with normal colonoscopy. CONCLUSIONS: Both low-risk and high-risk adenomas confer substantial risk for metachronous advanced colorectal neoplasia at 10 years. Positive fecal immunochemical test was a significant risk factor for metachronous advanced colorectal neoplasia despite normal colonoscopy.

Association of alcohol consumption with prevalence of fatty liver after adjustment for dietary patterns: Cross-sectional analysis of Japanese middle-aged adults.

BACKGROUND & AIMS: Moderate alcohol intake is associated with reduced prevalence or incidence of fatty liver. However, whether or not the association is independent of dietary patterns remains unclear. We aimed to evaluate the cross-sectional association of alcohol intake with fatty liver after accounting for dietary patterns and obesity. METHODS: We assessed 4579 adults aged 30-79 years who participated in routine clinical examinations in St. Luke's International Hospital, Japan (January to March, 2015). We assessed their habitual diet using diet-history questionnaire, estimated alcohol intake, and derived dietary pattern variables using factor analysis. Fatty liver was ascertained using ultrasonography. Linear and U-shaped associations of alcohol intake with fatty liver were evaluated using Poisson regression, and a post hoc analysis was conducted after detecting potential outliers for alcohol intake and excluding them using sex-specific statistics (median plus 2 × interquartile range). RESULTS: Fatty liver was ascertained in 1120 participants (24.5%). Whereas no significant association of alcohol intake with fatty liver was observed when potential outliers of alcohol intake were included (p = 0.25), a significant U-shaped association was observed after excluding the outliers with and without adjustment for dietary patterns (p = 0.003 and 0.02, respectively). The lowest prevalence was estimated when alcohol consumption was approximately 7% of energy, with a prevalence ratio of 0.72 (95% confidence interval = 0.59-0.86) compared to non-drinkers. The association became imprecise and attenuated toward the null after further adjustment for body mass index (p = 0.06). CONCLUSIONS: Alcohol intake showed a U-shaped association with fatty liver prevalence. This association was independent of underlying dietary patterns, while it was sensitive to excessive alcohol intake and obesity status, providing clinical implications for the prevention of fatty liver.

Primary gastric plasmacytoma refractory to Helicobacter pylori eradication therapy.

A 49-year-old woman underwent upper gastrointestinal endoscopic examination for epigastric discomfort, revealing giant folds on the greater curvature of the stomach. Histological examinations of biopsy specimens taken from the giant folds showed signs of chronic inflammation, and Helicobacter pylori was also identified. She underwent first-step H. pylori eradication. On follow-up endoscopy, H. pylori was not identified. However, endoscopic findings were unchanged and repeated biopsies showed dense infiltration of atypical plasma cells. No proliferation of centrocyte-like cells was seen. Immunohistochemically, plasma cells were positive for lambda-chain. Primary gastric plasmacytoma was diagnosed. Total gastrectomy was carried out with splenectomy and regional lymph node dissection. The patient remains disease free as of 6 years postoperatively.

No association between fruits or vegetables and non-alcoholic fatty liver disease in middle-aged men and women.

OBJECTIVE: It has been hypothesized that fruit and vegetable intake is inversely associated with non-alcoholic fatty liver (NAFLD). However, some studies have speculated that fruit intake might be positively associated with NAFLD owing to the fructose content of the fruit. This might cause consumers to hesitate consuming fruit. The aim of this study was to assess the association between fruit and vegetable consumption and NAFLD. METHODS: This was a cross-sectional study of 977 men and 1467 women, 40 to 69 y of age without current liver disease other than NAFLD and who did not report excess alcohol intake (i.e., ≥30 g/d in men and ≥20 g/d in women). Dietary intake was assessed using a validated diet history questionnaire. NAFLD was diagnosed from abdominal ultrasonography results. The association between quartiles of fruit or vegetable consumption and NAFLD prevalence was assessed using logistic regression analysis, with lowest category as reference. RESULTS: The prevalence of NAFLD was 34.9% in men and 11.7% in women. Adjusted for age and lifestyle factors, fruit intake was inversely associated with NAFLD in both sexes. However, these associations disappeared after further adjustment for body mass index. Consumption of total vegetables was not associated with NAFLD. In women, a linear inverse association was demonstrated between green and yellow vegetable intake and NAFLD in the final model (Ptrend = 0.04), but odds ratios for any intake category did not reach significance. CONCLUSIONS: No obesity-independent association was found between fruit or vegetable intake and NAFLD. According to the findings of this study, Japanese do not need to restrict fruit consumption to limit fructose intake as a means of preventing NAFLD.

Association between rice, bread, and noodle intake and the prevalence of non-alcoholic fatty liver disease in Japanese middle-aged men and women.

BACKGROUND & AIMS: Prevention of non-alcoholic fatty liver disease (NAFLD) through lifestyle modification is an important public health issue. Carbohydrate intake from soft drinks has received particular interest. Owing to differences in dietary habits, however, major contributors to the intake of dietary carbohydrates, such as rice, bread, and noodles, might have more influence on NAFLD prevalence in East Asian countries than consumption of soft drinks. We examined the relationship of the intake of rice, bread, and noodles, as well as overall carbohydrate intake, with NAFLD prevalence in middle-aged Japanese. METHODS: This is a cross-sectional study of 977 men and 1467 women aged 40-69 y. Dietary information was obtained using a validated self-administered diet history questionnaire. Diagnosis of NAFLD was based on the following criteria: presence of steatosis on abdominal ultrasound, alcohol intake <20 g/day in women and <30 g/day in men, and exclusion of other liver diseases. Logistic regression was performed as multivariate analysis. RESULTS: The presence of NAFLD was 34.9% (n = 341) in men and 11.7% (n = 171) in women. Carbohydrate intake was positively associated with NAFLD prevalence in women (p for trend = 0.008). There was also a positive association between rice intake and NAFLD prevalence in women; the multi-adjusted odds ratio for the highest versus the lowest quartiles of rice intake was 1.87 (95% CI: 1.03, 3.41; p for trend = 0.006). These associations were not observed in men. No association was observed between bread and noodle intake and the prevalence of NAFLD in either sex. CONCLUSIONS: Consumption of carbohydrates and rice was positively associated with NAFLD prevalence in middle-aged Japanese women.

Novel equations better predict lung age: a retrospective analysis using two cohorts of participants with medical check-up examinations in Japan.

BACKGROUND: The lung age equations developed by the Japanese Respiratory Society encounter several problems when being applied in a clinical setting. AIMS: To establish novel spirometry-derived lung age (SDL age) equations using data from a large number of Japanese healthy never-smokers with normal spirometric measurements and normal body mass indices (BMIs). METHODS: The participants had undergone medical check-ups at the Center for Preventive Medicine of St Luke's International Hospital between 2004 and 2012. A total of 15,238 Japanese participants (5,499 males and 9,739 females) were chosen for the discovery cohort. The other independent 2,079 individuals were selected for the validation cohort. The original method of Morris and Temple was applied to the discovery cohort. RESULTS: As a result of the linear regression analysis for forced expiratory volume in 1 s (FEV1), spirometric variables using forced vital capacity (FVC) improved the adjusted R(2) values to greater than 0.8. On the basis of the scatter plots between chronological age and SDL age, the best model included the equations using FEV1 and %FVC in females and males (R(2)=0.66 and 0.55, respectively), which was confirmed by the validation cohort. The following equations were developed: SDL age (females)=0.84×%FVC+50.2-40×FEV1 (l) and SDL age (males)=1.00×%FVC+50.7-33.3×FEV1 (l). CONCLUSIONS: This study produced novel SDL age equations for Japanese adults using data from a large number of healthy never-smokers with both normal spirometric measurements and BMIs.

Longitudinal Study of the Decline in Renal Function in Healthy Subjects.

BACKGROUND: Chronic kidney disease is an important concern in preventive medicine, but the rate of decline in renal function in healthy population is not well defined. The purpose of this study was to determine reference values for the estimated glomerular filtration rate (eGFR) and rate of decline of eGFR in healthy subjects and to evaluate factors associated with this decline using a large cohort in Japan. METHODS: Retrospective cross-sectional and longitudinal studies were performed with healthy subjects aged ≥18 years old who received a medical checkup. Reference values for eGFR were obtained using a nonparametric method and those for decline of eGFR were calculated by mixed model analysis. Relationships of eGFR decline rate with baseline variables were examined using a linear least-squares method. RESULTS: In the cross-sectional study, reference values for eGFR were obtained by gender and age in 72,521 healthy subjects. The mean (±SD) eGFR was 83.7±14.7 ml/min/1.73 m2. In the longitudinal study, reference values for eGFR decline rate were obtained by gender, age, and renal stage in 45,586 healthy subjects. In the same renal stage, there was little difference in the rate of decline regardless of age. The decline in eGFR depended on the renal stage and was strongly related to baseline eGFR, with a faster decline with a higher baseline eGFR and a slower decline with a lower baseline eGFR. The mean (±SD) eGFR decline rate was ‒1.07±0.42 ml/min/1.73 m2/year (‒1.29±0.41%/year) in subjects with a mean eGFR of 81.5±11.6 ml/min/1.73 m2. CONCLUSIONS: The present study clarified for the first time the reference values for the rate of eGFR decline stratified by gender, age, and renal stage in healthy subjects. The rate of eGFR decline depended mainly on baseline eGFR, but not on age, with a slower decline with a lower baseline eGFR.

Diagnostic performance of quantitative fecal immunochemical test and multivariate prediction model for colorectal neoplasms in asymptomatic individuals.

OBJECTIVE: Quantitative fecal immunochemical test (QTFIT) has the advantage of being able to describe test characteristics on a scaled rather than binary system. The aims of this study were to decide the optimal cut-off points of QTFIT and to make a multivariate prediction model for colorectal neoplasms in asymptomatic adults. MATERIALS AND METHODS: We retrospectively analyzed 1085 consecutive asymptomatic individuals who completed both full colonoscopy and QTFIT at a general health checkup clinic. Advanced adenomatous polyps (AP) were defined as APs of at least 1 cm in diameter; adenomas with villous component or high-grade dysplasia; and significant neoplasia (SN) including both advanced AP and colorectal cancer. RESULTS: The ideal cut-off value of QTFIT was chosen based on a value that maximized the sum of both sensitivity and specificity, and clinical utility. For AP, 25 ng/ml was chosen as the optimal cut-off value and provided a sensitivity of 31% [95% confidence interval (CI): 27-36] and specificity of 79% (95% CI: 76-82). For SN, the ideal QTFIT cut-off value was 25 ng/ml, providing a sensitivity of 51% (95% CI: 39-62) and specificity of 77% (95% CI: 74-80). For colorectal cancer, the optimal cut-off point was 50 ng/ml, offering a sensitivity of 75% (95% CI: 41-93) and specificity of 86% (95% CI: 85-86). The multivariate prediction model was represented by nomogram and was validated by bootstrap method. CONCLUSION: The diagnostic performance of QTFIT for CRC is promising, although its sensitivity for AP and SN is unsatisfactory. BMI, in addition to age and sex improves the accuracy of SN screening by QTFIT.

Hemodynamic assessment of the left gastric vein in patients with esophageal varices with color Doppler EUS: factors affecting development of esophageal varices.

BACKGROUND: An understanding of the development of esophageal varices is important in the evaluation of risk of variceal hemorrhage. To clarify factors affecting the development of esophageal varices, the morphology and hemodynamics of the left gastric vein were analyzed with color Doppler EUS. METHODS: Sixty-seven patients with esophageal varices underwent color Doppler EUS. Seventeen had small varices (F1), 32 had medium varices (F2), and 18 had large varices (F3). RESULTS: Hepatofugal blood flow velocity in the left gastric vein trunk increased as the size of the varices increased (p < 0.0001), whereas the diameter did not increase. The left gastric vein bifurcates into anterior and posterior branches. As the size of the varices enlarged, the branch pattern was more likely to be anterior branch dominant (p = 0.041). There was no significant difference between the 3 size groups of esophageal varices with respect to the size of the paraesophageal collaterals. The detection rate and diameter of the perforating vein increased as the size of the varices increased (p = 0.032 and 0.012, respectively). CONCLUSION: Blood flow velocity in the left gastric vein trunk, branches, and perforating veins may regulate blood flow supplying the esophageal varices and contribute to their development. These findings are important to understanding the pathogenesis of esophageal varices.