Genome-wide association study of metabolic dysfunction-associated fatty liver disease in a Korean population.

Genome-wide association studies have identified several genetic variants associated with nonalcoholic fatty liver disease. To emphasize metabolic abnormalities in fatty liver, metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been introduced; thus, we aimed to investigate single-nucleotide polymorphisms related to MAFLD and its subtypes. A genome-wide association study was performed to identify genetic factors related to MAFLD. We used a Korean population-based sample of 2282 subjects with MAFLD and a control group of 4669. We replicated the results in a validation sample which included 639 patients with MAFLD and 1578 controls. Additionally, we categorized participants into three groups, no MAFLD, metabolic dysfunction (MD)-MAFLD, and overweight/obese-MAFLD. After adjusting for age, sex, and principal component scores, rs738409 [risk allele G] and rs3810622 [risk allele T], located in the PNPLA3 gene, showed significant associations with MAFLD (P-values, discovery set = 1.60 × 10-15 and 4.84 × 10-10; odds ratios, 1.365 and 1.284, validation set = 1.39 × 10-4, and 7.15 × 10-4, odds ratios, 1.299 and 1.264, respectively). An additional SNP rs59148799 [risk allele G] located in the GATAD2A gene showed a significant association with MAFLD (P-values, discovery set = 2.08 × 10-8 and validation set = 0.034, odds ratios, 1.387 and 1.250). rs738409 was significantly associated with MAFLD subtypes ([overweight/obese-MAFLD; odds ratio (95% confidence interval), P-values, 1.515 (1.351-1.700), 1.43 × 10-12 and MD-MAFLD: 1.300 (1.191-1.416), 2.90 × 10-9]. There was a significant relationship between rs3810622 and overweight/obese-MAFLD and MD-MAFLD [odds ratios (95% confidence interval), P-values, 1.418 (1.258, 1.600), 1.21 × 10-8 and 1.225 (1.122, 1.340), 7.06 × 10-6, respectively]; the statistical significance remained in the validation set. PNPLA3 was significantly associated with MAFLD and MAFLD subtypes in the Korean population. These results indicate that genetic factors play an important role in the pathogenesis of MAFLD.

Physical activity has a more beneficial effect on the risk of all-cause mortality in patients with metabolic syndrome than in those without.

BACKGROUND: It has not been clarified whether physical activity (PA) has more benefit in terms of health outcomes, including mortality risk, among those with metabolic syndrome (MS) compared to those without. Therefore, the aim of this study is to elucidate whether regular PA has interaction with MS on health outcomes. METHODS: Participants with no underlying cardiovascular diseases who underwent national health screening in 2009 were included. According to the metabolic equivalent (MET)-minutes/week, the amount of PA among the participants was grouped as follows: Group 1 (0 MET-minutes/week), Group 2 (1-499), Group 3 (500-999), Group 4 (1000-1499), and Group 5 (≥ 1500). Multivariable Cox proportional hazard models were applied to evaluate the impacts of the amount of PA on health outcomes among those with and without MS. Health outcomes included all-cause mortality and incident cardiovascular diseases (CVDs). RESULTS: Of 9,628,109 total participants, 335,970 deaths occurred during a median 8.3-year follow-up. After adjustment for age, sex, smoking status, alcohol consumption, and body mass index, the higher the PA amount was, the lower the risk of all-cause mortality in both those with MS [adjusted hazard ratio (aHR) compared with Group 1, 0.86 (95% CI 0.85, 0.87) in Group 2; 0.82 (95% CI 0.81, 0.83) in Group 3; 0.75 (95% CI 0.74, 0.77) in Group 4; and 0.78 (95% CI 0.76, 0.80) in Group 5; P for trend < 0.001] and those without MS [aHR compared with Group 1, 0.87 (95% CI 0.86, 0.88) in Group 2; 0.84 (95% CI 0.83, 0.85) in Group 3, 0.79 (95% CI 0.78, 0.80) in Group 4, and 0.82 (95% CI 0.81, 0.84) in Group 5; P for trend < 0.001]. The beneficial effects of the amount of PA on all-cause mortality were larger among those with MS than among those without MS in a multiplicative interaction (P for interaction < 0.001). The results were similar in the analysis of the relationship between the PA amount and incident CVD. CONCLUSIONS: More PA was associated with a lower risk of all-cause mortality, which was more prominent in those with MS than in those without MS. Physicians should emphasize more the importance of PA in patients with MS.

Development and validation of a convolutional neural network model for diagnosing Helicobacter pylori infections with endoscopic images: a multicenter study.

BACKGROUND AND AIMS: Insufficient validation limits the generalizability of deep learning in diagnosing Helicobacter pylori infection with endoscopic images. The aim of this study was to develop a deep learning model for the diagnosis of H pylori infection using endoscopic images and validate the model with internal and external datasets. METHODS: A convolutional neural network (CNN) model was developed based on a training dataset comprising 13,403 endoscopic images from 952 patients who underwent endoscopy at Seoul National University Hospital Gangnam Center. Internal validation was performed using a separate dataset comprised of images of 411 individuals of Korean descent and 131 of non-Korean descent. External validation was performed with the images of 160 patients in Gangnam Severance Hospital. Gradient-weighted class activation mapping was performed to visually explain the model. RESULTS: In predicting H pylori ever-infected status, the sensitivity, specificity, and accuracy of internal validation for people of Korean descent were .96 (95% confidence interval [CI], .93-.98), .90 (95% CI, .85-.95), and .94 (95% CI, .91-.96), respectively. In the internal validation for people of non-Korean descent, the sensitivity, specificity, and accuracy in predicting H pylori ever-infected status were .92 (95% CI, .86-.98), .79 (95% CI, .67-.91), and .88 (95% CI, .82-.93), respectively. In the external validation cohort, sensitivity, specificity, and accuracy were .86 (95% CI, .80-.93), .88 (95% CI, .79-.96), and .87 (95% CI, .82-.92), respectively, when performing 2-group categorization. Gradient-weighted class activation mapping showed that the CNN model captured the characteristic findings of each group. CONCLUSIONS: This CNN model for diagnosing H pylori infection showed good overall performance in internal and external validation datasets, particularly in categorizing patients into the never- versus ever-infected groups.

The relationship between metabolic dysfunction-associated fatty liver disease and low muscle mass in an asymptomatic Korean population.

BACKGROUND: Metabolic (dysfunction)-associated fatty liver disease (MAFLD) emphasizes the metabolic dysfunction in nonalcoholic fatty liver disease (NAFLD). Although the relationship between low muscle mass and NAFLD has been suggested, the effect of MAFLD on low muscle mass is yet to be investigated. In this study, we examined the relationship between MAFLD and low muscle mass in an asymptomatic Korean population. METHODS: Examinees who underwent FibroScan® and bioelectrical impedance analyses on the same day during the period of June 2017 to December 2019 were included. Hepatic steatosis was diagnosed using controlled attenuation parameter (CAP) with two cut-off values of 248 and 294 dB/m. Low muscle mass was defined based on appendicular skeletal muscle mass/body weight (wt) or body mass index (BMI) ratios of two standard deviations below the sex-specific mean for healthy young adults. Subjects were divided into four subgroups: diabetic MAFLD (presence of diabetes mellitus [DM]), metabolic dysfunction (MD) MAFLD (≥2 metabolic abnormalities without DM), overweight MAFLD (overweight/obese without DM and <2 metabolic abnormalities) and no MAFLD. RESULTS: Among all of the 6414 subjects (mean 53.9 years of age; 85.4% male), the prevalence of MAFLD was 49.9% and 22.7% for CAP cut-off values of 248 and 294 dB/m, respectively. In the multivariate analysis, MAFLD was associated with an increased risk of both low muscle mass_wt (odds ratio [OR] 1.80, 95% confidence interval [CI] 1.38-2.35, P < 0.001) and low muscle mass_BMI (OR 1.31, 95% CI 1.01-1.70, P = 0.042). The risk of low muscle mass_wt and low muscle mass_BMI increased the most in the diabetic MAFLD subgroup compared with the no-MAFLD group (OR 2.11, 95% CI 1.51-2.96, P < 0.001 and OR 1.51, 95% CI 1.08-2.13, P = 0.017). There was an increased risk of low muscle mass_wt in the MD MAFLD subgroup (OR 1.73, 95% CI 1.31-2.28, P < 0.001). Comparable results were observed when the CAP cut-off value of 294 dB/m was applied. CONCLUSIONS: The presence of MAFLD is significantly associated with increased risk of low muscle mass with varying risks according to the MAFLD subgroups. Clinicians should be aware of the differentiated risk of low muscle mass across the subgroups of MAFLD.

Impact of comprehensive optical diagnosis training using Workgroup serrAted polypS and Polyposis classification on detection of adenoma and sessile serrated lesion.

OBJECTIVES: Many interventions have been attempted to improve adenoma detection rate (ADR) and sessile serrated lesion detection rate (SDR), and one of these interventions is educational training to recognize polyp characteristics. This study aimed to investigate the change in polyp detection rates of endoscopists before and after comprehensive training through the Gangnam-Real Time Optical Diagnosis (Gangnam-READI) program. METHODS: Fifteen gastroenterologists participated in a 1-year comprehensive training program that consisted of ex vivo and in vivo training that encompasses knowledge and skills in endoscopic characterization of colonic polyps using the Workgroup serrAted polypS and Polyposis (WASP) classification. We evaluated the impact of the training program by comparing the overall and individual ADR and SDR 6 months before and after the training. RESULTS: Overall, 18,280 polyps (9337 adenomas and 855 sessile serrated lesion) were collected. The optical diagnosis training had no significant impact on the difference in ADR after training compared to before training (47.7% vs. 46.5%, P = 0.608). A tendency for a decrease in ADR variance was noted among the endoscopists after training (74.9 vs. 32.7, P = 0.121). The overall pre-training period SDR was 4.5% and showed a statistically significant increase to 5.6%, 8.0%, and 7.1% in the first and second half of the training period, and post-training period, respectively (P = 0.003). The optical diagnosis training did not decrease variance in SDR (8.9 vs. 8.8, P = 0.985). CONCLUSION: Comprehensive optical diagnosis training with WASP classification has a significant impact on increasing the overall SDR of expert endoscopists.

Progression Rates by Age, Sex, Treatment, and Disease Activity by AASLD and EASL Criteria: Data for Precision Medicine.

BACKGROUND & AIMS: Antiviral treatment criteria are based on disease progression risk, and hepatocellular carcinoma (HCC) surveillance recommendations for patients with chronic hepatitis B (CHB) without cirrhosis is based on an annual incidence threshold of 0.2%. However, accurate and precise disease progression estimate data are limited. Thus, we aimed to determine rates of cirrhosis and HCC development stratified by age, sex, treatment status, and disease activity based on the 2018 American Association for the Study of Liver Diseases and 2017 European Association for the Study of the Liver guidelines. METHODS: We analyzed 18,338 patients (8914 treated, 9424 untreated) from 6 centers from the United States and 27 centers from Asia-Pacific countries. The Kaplan-Meier method was used to estimate annual progression rates to cirrhosis or HCC in person-years. RESULTS: The cohort was 63% male, with a mean age of 46.19 years, with baseline cirrhosis of 14.3% and median follow up of 9.60 years. By American Association for the Study of Liver Diseases criteria, depending on age, sex, and disease activity, annual incidence rates ranged from 0.07% to 3.94% for cirrhosis, from 0.04% to 2.19% for HCC in patients without cirrhosis, and from 0.40% to 8.83% for HCC in patients with cirrhosis. Several subgroups of patients without cirrhosis including males younger than 40 years of age and females younger than 50 years of age had annual HCC risk near or exceeding 0.2%. Similar results were found using European Association for the Study of the Liver criteria. CONCLUSION: There is great variability in CHB disease progression rates even among "lower-risk" populations. Future CHB modeling studies, public health planning, and HCC surveillance recommendation should be based on more precise disease progression rates based on sex, age, and disease activity, plus treatment status.

Continuing regular physical activity and maintaining body weight have a synergistic interaction in improving survival: a population-based cohort study including 6.5 million people.

AIMS: Continuing physical activity (PA) and maintaining body weight are tightly intertwined; however, no study investigated whether these two factors have interactions in terms of the mortality. The aim of this study is to elucidate whether continuing regular PA and maintaining body weight have interactions in terms of all-cause mortality risk. METHODS AND RESULTS: Participants with health screening from both 2009 and 2011 without underlying cancer or cardiovascular disease were included. Physical activity change was grouped as remained active, inactive-to-active, active-to-inactive, or remained inactive. Body weight change was categorized as stable (weight change < 5%), weight gain, or loss. Outcome included all-cause mortality. Of 6 572 984 total participants, 91 347 deaths occurred during a median 7.4-year follow-up. Compared with the remained active and stable weight group, most other groups had a higher mortality risk. The weight loss and remained inactive group [adjusted hazard ratio (aHR), 2.30; 95% confidence interval (CI), 2.22-2.38] and the weight gain and remained inactive group (aHR, 2.17; 95% CI, 2.09-2.25) showed the highest mortality risks. Among stable weight participants, the ranking of the groups from highest to lowest in terms of mortality risk was as follows: remained inactive (aHR, 1.46; 95% CI, 1.41-1.50), active-to-inactive (aHR, 1.24; 95% CI, 1.19-1.29), inactive-to-active (aHR, 1.15; 95% CI, 1.11-1.20), and remained active (reference). Remaining active and maintaining a stable body weight had a synergistic interaction on decreasing all-cause mortality risk (multiplicative P for interaction < 0.001; relative excess risk due to interaction, 0.38; 95% CI, 0.31-0.46; attributable proportion, 0.18; 95% CI, 0.15-0.22). CONCLUSIONS: Continuing regular PA as recommended and maintaining body weight have multiplicative and additive interactions on reducing all-cause mortality. Healthcare providers should emphasize the importance of both regular PA and body weight maintenance for the general public.

The association between Helicobacter pylori with nonalcoholic fatty liver disease assessed by controlled attenuation parameter and other metabolic factors.

AIM: Existing studies have suggested an association between Helicobacter pylori (Hp) infection and nonalcoholic fatty liver disease (NAFLD). We investigated the relationship between Hp infection and NAFLD using controlled attenuation parameter (CAP) and other metabolic factors. METHOD: We conducted a retrospective cohort study of apparently healthy individuals who underwent liver Fibroscan during health screening tests between January 2018 and December 2018. Diagnosis of Hp infection was based on a serum anti-Hp IgG antibody test and CAP values were used to diagnose NAFLD. RESULTS: Among the 1,784 subjects (mean age 55.3 years, 83.1% male), 708 (39.7%) subjects showed positive results of Hp serology. In the multivariate analysis, obesity (body mass index ≥25) (odds ratio [OR] 3.44, 95% confidence interval [CI] 2.75-4.29), triglyceride (OR 2.31, 95% CI 1.80-2.97), and the highest tertile of liver stiffness measurement (OR 2.08, 95% CI 1.59-2.71) were found to be associated with NAFLD, defined by CAP ≥248 dB/m, while Hp-seropositivity showed no association with NAFLD. Serum levels of HDL cholesterol significantly decreased in subjects with Hp-seropositivity compared to HP-seronegativity in both groups with and without NAFLD (P<0.001). CONCLUSION: While Hp seropositivity was not associated with CAP-defined NAFLD, serum HDL cholesterol level were negatively associated with Hp-seropositivity in both groups with and without NAFLD. Further clinical and experimental studies are necessary to determine the association between Hp infection and NAFLD.

Fatty Liver Index for Predicting Nonalcoholic Fatty Liver Disease in an Asymptomatic Korean Population.

Nonalcoholic fatty liver disease (NAFLD) is increasing worldwide, highlighting the importance of early and accurate detection and the appropriate management of NAFLD. However, ultrasonography (US) is not included in many mass screening programs, and people have limited access to it. The aim of this study is to validate the fatty liver index (FLI) and investigate the optimal cutoff value for predicting NAFLD in an asymptomatic population. We conducted a retrospective cohort study in Korea. All subjects who underwent health checkup exams, including abdominal US, controlled attenuation parameter (CAP) and blood testing, were enrolled. Analyses of the area under the receiver operating characteristic curve (AUROC) were used to evaluate the diagnostic accuracy and to calculate the optimal FLI cutoff for US-NAFLD. Among the 4009 subjects (mean age 54.9 years, 83.5% male), the prevalence of US-diagnosed NAFLD and CAP-defined hepatic steatosis was 61.4% and 55.4%. The previously used cutoff of FLI = 60 showed poor performance in predicting US-diagnosed NAFLD, with an AUROC of 0.63 (0.62-0.64), and CAP-defined NAFLD, with an AUROC 0.63 (0.62-0.64). The optimal FLI cutoff values to discriminate fatty liver detected by US were 29 for the entire population, with an AUROC of 0.82 (0.81-0.84). The sex-specific values were 31 for males and 18 for females (sensitivity 72.8% and 73.4%; specificity 74.2% and 85.0%, respectively). The FLI cutoff for US-diagnosed NAFLD can be set as 29 for the entire Korean population. Considering the sex dimorphism in NAFLD, different cutoff values are suggested to predict US-diagnosed NAFLD. These results may be helpful in the accurate non-invasive diagnosis of NAFLD.

The Risk of Colorectal Adenoma in Nonalcoholic or Metabolic-Associated Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease associated with various metabolic disorders. Metabolic dysfunction-associated fatty liver disease (MAFLD) emphasizes metabolic dysfunction in NAFLD. Although the relationship between NAFLD and colorectal adenomas has been suggested, the effect of MAFLD on colorectal adenoma has yet to be investigated. In this study, we examined the relationship between NAFLD/MAFLD and colorectal adenoma in comparison with other metabolic factors. METHODS: Examinees who underwent colonoscopy and abdominal ultrasonography on the same day from January 2012 to December 2012 were included. NAFLD was diagnosed according to the findings of ultrasonography. The Fibrosis-4 (FIB-4) index was used as a surrogate marker for advanced hepatic fibrosis. A logistic regression model was used to analyze the risk of NAFLD/MAFLD for colorectal adenoma. RESULTS: The prevalence of NAFLD and MAFLD was 37.5% and 32.8%, respectively. In the multivariate analysis, male sex, older age, diabetes, and smoking increased the risk of colorectal adenoma. NAFLD and MAFLD were the most important risk factors for colorectal adenoma only in females [adjusted odds ratio (OR) 1.43 and 95% confidence interval (CI) 1.01-2.03, and OR 1.55, 95% CI 1.09-2.20, respectively]. NAFLD and MAFLD with an advanced fibrosis index were significantly associated with an increased risk of colorectal adenoma. (NAFLD: OR 1.38, 95% CI, 1.04-1.83, p = 0.027; MAFLD: OR 1.45, 95% CI, 1.13-1.96, p = 0.004, respectively). CONCLUSION: NAFLD and MAFLD were significantly associated with a higher risk of colorectal adenomas, especially in females. NAFLD and MAFLD with advanced fibrosis were associated with an increased risk of colorectal adenoma. Colonoscopic examinations may be emphasized for patients with NAFLD/MAFLD, for women, or patients with the presence of hepatic fibrosis.

Hepatic fibrosis is associated with an increased rate of decline in bone mineral density in men with nonalcoholic fatty liver disease.

BACKGROUND: There is still controversy about the association between nonalcoholic fatty liver disease (NAFLD) and bone mineral density (BMD). The aim of this study was to clarify the association between NAFLD and the decline in BMD in healthcare examinees. METHODS: Participants who underwent regular health check-ups with BMD and hepatic ultrasonography from 2006 to 2015 with more than one follow-up until 2020 were included. Propensity score matching was performed between the NAFLD group and the control group, and mixed linear regression models were used for the longitudinal analysis. RESULTS: Of 2623 eligible participants (mean age 58.7 ± 7.3 years; males 31.3%), 888 (33.9%) had NAFLD. At baseline, the NAFLD group had a higher total hip BMD than the non-NAFLD group in men (0.988 vs. 1.015 g/cm2, p = 0.007); however, there was no difference in baseline BMD in women (p = 0.253). In longitudinal analysis during a follow-up period of 7.1 years, there was no significant difference in the BMD decline rate between the two groups in the PS-matched cohort (p = 0.816 in men and p = 0.827 in women). However, among men with NAFLD, those with a high and intermediate probability of advanced fibrosis by the FIB-4 showed a significantly increased rate of decline in total hip BMD compared to those with low scores (0.01 vs. - 0.19% change/year, p = 0.011). CONCLUSIONS: NAFLD was not associated with the total hip BMD decline rate. However, hepatic fibrosis was significantly associated with an increased rate of decline in total hip BMD in men with NAFLD. CLINICAL TRIAL REGISTRATION: This study is a retrospective observational study and is not a drug trial. There was no need for clinical trial registration.

The Association between Low Muscle Mass and Hepatic Steatosis in Asymptomatic Population in Korea.

BACKGROUND: An association between low muscle mass and nonalcoholic fatty liver disease (NAFLD) has been suggested. We investigated this relationship using controlled attenuation parameter (CAP). METHODS: A retrospective cohort of subjects had liver FibroScan® (Echosens, Paris, France) and bioelectrical impedance analyses during health screening exams. Low muscle mass was defined based on appendicular skeletal muscle mass/body weight ratios of one (class I) or two (class II) standard deviations below the sex-specific mean for healthy young adults. RESULTS: Among 960 subjects (58.1 years; 67.4% male), 344 (45.8%, class I) and 110 (11.5%, class II) had low muscle mass. After adjusting for traditional metabolic risk factors, hepatic steatosis, defined as a CAP ≥ 248 dB/m, was associated with low muscle mass (class I, odds ratio (OR): 1.96, 95% confidence interval (CI): 1.38-2.78; class II, OR: 3.33, 95% CI: 1.77-6.26). A dose-dependent association between the grade of steatosis and low muscle mass was also found (class I, OR: 1.88, for CAP ≥ 248, <302; OR: 2.19, in CAP ≥ 302; class II, OR: 2.33, for CAP ≥ 248, <302; OR: 6.17, in CAP ≥ 302). High liver stiffness was also significantly associated with an increased risk of low muscle mass (class I, OR: 1.97, 95% CI: 1.31-2.95; class II, OR: 2.96, 95% CI: 1.51-5.78). CONCLUSION: Hepatic steatosis is independently associated with low muscle mass in a dose-dependent manner. The association between hepatic steatosis and low muscle mass suggests that particular attention should be given to subjects with NAFLD for an adequate assessment of muscle mass.

Fully automated waist circumference measurement on abdominal CT: Comparison with manual measurements and potential value for identifying overweight and obesity as an adjunct output of CT scan.

OBJECTIVE: Waist circumference (WC) is a widely accepted anthropometric parameter of central obesity. We investigated a fully automated body segmentation algorithm for measuring WC on abdominal computed tomography (CT) in comparison to manual WC measurements (WC-manual) and evaluated the performance of CT-measured WC for identifying overweight/obesity. MATERIALS AND METHODS: This retrospective study included consecutive adults who underwent both abdominal CT scans and manual WC measurements at a health check-up between January 2013 and November 2019. Mid-waist WCs were automatically measured on noncontrast axial CT images using a deep learning-based body segmentation algorithm. The associations between CT-measured WC and WC-manual was assessed by Pearson correlation analysis and their agreement was assessed through Bland-Altman analysis. The performance of these WC measurements for identifying overweight/obesity (i.e., body mass index [BMI] ≥25 kg/m2) was evaluated using receiver operating characteristics (ROC) curve analysis. RESULTS: Among 763 subjects whose abdominal CT scans were analyzed using a fully automated body segmentation algorithm, CT-measured WCs were successfully obtained in 757 adults (326 women; mean age, 54.3 years; 64 women and 182 men with overweight/obesity). CT-measured WC was strongly correlated with WC-manual (r = 0.919, p < 0.001), and showed a mean difference of 6.1 cm with limits of agreement between -1.8 cm and 14.0 cm in comparison to WC-manual. For identifying overweight/obesity, CT-measured WC showed excellent performance, with areas under the ROC curve (AUCs) of 0.960 (95% CI, 0.933-0.979) in women and 0.909 (95% CI, 0.878-0.935) in men, which were comparable to WC-manual (AUCs of 0.965 [95% CI, 0.938-0.982] and 0.916 [95% CI, 0.886-0.941]; p = 0.735 and 0.437, respectively). CONCLUSION: CT-measured WC using a fully automated body segmentation algorithm was closely correlated with manually-measured WC. While radiation issue may limit its general use, it can serve as an adjunctive output of abdominal CT scans to identify overweight/obesity.

Body weight gain rather than body weight variability associated with increased risk of nonalcoholic fatty liver disease.

Weight loss, the most established therapy for nonalcoholic fatty liver disease (NAFLD), is frequently followed by weight regain and fluctuation. The aim of this study was to investigate whether body weight change and variability were independent risk factors for incident NAFLD. We conducted a longitudinal cohort study. Among the 1907 participants, incident NAFLD occurred in 420 (22.0%) cases during median follow-up of 5.6 years. In the multivariate analysis, there was no significant association between weight variability and the risk of incident NAFLD. The risk of incident NAFLD was significantly higher in subjects with weight gain ≥ 10% and 7% < gain ≤ 10% [hazard ratios (HR), 2.43; 95% confidence intervals (CI), 1.65-3.58 and HR, 1.73; 95% CI, 1.26-2.39, respectively], while the risk of incident NAFLD was significantly lower in those with -7% < weight loss ≤ --3% (HR, 0.33; 95% CI, 0.22-0.51). Overall body weight gain rather than bodyweight variability was independently associated with the risk of incident NAFLD. Understanding the association between body weight variability and incident NAFLD may have future clinical implications for the quantification of weight loss as a treatment for patients with NAFLD.

The Association between Vitamin D and Nonalcoholic Fatty Liver Disease Assessed by Controlled Attenuation Parameter.

BACKGROUND: An association between nonalcoholic fatty liver disease (NAFLD) and low vitamin D levels has been suggested. We investigated the relationship between vitamin D and NAFLD assessed by controlled attenuation parameter (CAP). METHODS: We conducted a retrospective cohort study of apparently healthy subjects who underwent Fibroscan during health screening tests. NAFLD was diagnosed using CAP values. RESULTS: Among the 1202 subjects (mean age 57.2 years, 60.6% male), 630 (52.4%) subjects had NAFLD with CAP ≥ 248 dB/m. Multivariable analysis was conducted after adjusting for metabolic risk factors including diabetes, hypertension, hypercholesterolemia, body mass index, high-density lipoprotein cholesterol, triglyceride and smoking. Higher vitamin D levels showed a lower risk of NAFLD compared to the lowest quartile of vitamin D in a dose-dependent manner (OR 0.68, 95% CI 0.47-1.00 in Q2 vs. Q1; OR 0.65, 95% CI 0.44-0.94 in Q3 vs. Q1; and OR 0.64, 95% CI 0.44-0.94 in Q4 vs. Q1). The highest quartile of vitamin D showed a decreased risk of a severe grade of steatosis (CAP ≥ 302 dB/m) compared to the lowest quartile (OR 0.52, 95% CI 0.31-0.87 in Q4 vs. Q1). CONCLUSIONS: Higher levels of serum vitamin D were associated with a decreased risk of CAP-defined NAFLD, compared to low levels of serum vitamin D. The association between NAFLD and vitamin D suggests that vitamin D may exert a protective role against NAFLD.

Synergistic harmful interaction between sustained physical inactivity and hypertension/diabetes mellitus on the risk of all-cause mortality: a retrospective observational cohort study.

OBJECTIVE: Hypertension, diabetes mellitus and physical inactivity can cause cardiovascular complications or premature death. However, it has not been clarified whether those major comorbidities and physical activity interact in affecting health outcomes. The aim of this study is to evaluate the potential interaction between temporal physical activity profiles and hypertension or diabetes mellitus on the risk for all-cause mortality. METHODS: This study used Korea National Health Insurance Service (KNHIS) database and included about 6.5 million participants who underwent health screening in 2009 and 2011. Physical activity was evaluated as 2-year change based on self-reported survey using 7-day recall method, and grouped as remained active, inactive-to-active, active-to-inactive, or remained inactive. Participants were categorized into groups according to the presence of hypertension/diabetes mellitus. Outcome included all-cause mortality. RESULTS: In total, 6 554 082 participants (48.4 ±â€Š13.3 years; 56.7% men) were included. During a median 6.4-year follow-up, 83 241 deaths occurred. Compared with the 'remained active' group, other groups had a higher mortality risk after adjustment for covariates [adjusted hazard ratio (aHR) 1.17, 95% CI 1.13-1.21 in the 'inactive-to-active' group, aHR 1.28, 95% CI 1.24-1.32 in the 'active-to-inactive' group, aHR 1.52, 95% CI 1.48-1.57 in the 'remained inactive' group). Hypertension and diabetes mellitus were significant effect modifiers in the association between physical activity and the risk of all-cause mortality (P for interaction <0.001). The harmful effects of persistent physical inactivity on all-cause mortality were the most obvious in those with both hypertension and diabetes mellitus among groups. CONCLUSION: Sustained physical inactivity was associated with increased risk of all-cause mortality in those with hypertension or diabetes mellitus more strongly than in those without. Physicians should emphasize sustained physical activity even more in patients with hypertension or diabetes mellitus.

The Repeatedly Elevated Fatty Liver Index Is Associated With Increased Mortality: A Population-Based Cohort Study.

Aims: Non-alcoholic fatty liver disease (NAFLD) has a dynamic disease course, therefore repeated measurements of NAFLD status could have benefits rather than single one. The aim of this study was to investigate the effects of persistent NAFLD on the incidence of myocardial infarction (MI) and stroke and all-cause mortality by using repeated measurement of fatty liver index (FLI). Methods: About 3 million subjects who had undergone the health screening four times from 2009 until 2013 were included. NAFLD was defined as an FLI ≥60. FLI points were defined as the number of times participants meeting the criteria of NAFLD (0-4). Outcomes included all-cause mortality, MI, and stroke. Results: The higher the FLI points, the higher the risk of all-cause mortality, MI, and stroke (P for trend <0.001, all). Subjects with four FLI points had a higher risk of all-cause mortality (aHR, 1.86; 95% CI, 1.75-1.98; P < 0.001), incidence of MI (aHR, 1.3; 95% CI, 1.21-1.40; P < 0.001), and stroke (aHR, 1.27; 95% CI, 1.19-1.37; P < 0.001) after adjustment for age, sex, smoking, alcohol consumption, income, hypertension, dyslipidemia, diabetes, body mass index, and physical activity. When the 1st and the last FLI were compared, the "incident NAFLD" group had a higher risk for death compared to the "no NAFLD" group (aHR, 1.46; 95% CI, 1.37-1.55), and the "regression of NAFLD" group had a decreased risk for death compared to the "persistent NAFLD" group (aHR, 0.83; 95% CI, 0.77-0.89). Conclusion: Repeated evaluations of NAFLD status based on FLI measurements could help physicians identify higher-risk groups in terms of mortality, MI, and stroke. The association between FLI worsening or improvement and outcomes also suggests clinical benefits of the prevention and treatment of NAFLD.