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.

The risk of colorectal cancer according to obesity status at four-year intervals: a nationwide population-based cohort study.

Obesity is a risk factor for colorectal cancer. However, the effect of body weight change on colorectal cancer is uncertain. This study aimed to investigate the relationship between difference in body mass index and the risk of colorectal cancer. In this nationwide population-based cohort study, participants of the national cancer screening program in 2005 and 2009 were enrolled. Difference of body mass index was calculated from screening data from 2005 and 2009. Participants were divided into four groups according to direction of obesity status: non-obese/non-obese, non-obese/obese, obese/non-obese, and obese/obese. The effect of differences in body mass index on colorectal cancer was analyzed. Among 3,858,228 participants, 47,894 (1.24%) participants were newly diagnosed with colorectal cancer during the 9.2 years of follow-up. The incidence of colorectal cancer was higher in the obese/obese group than the non-obese/non-obese group (hazard ratio = 1.08 [1.06-1.11], P trend < 0.001). The men in the obese/obese group had a higher risk of colon cancer than women (hazard ratio = 1.13 [1.10-1.17] in men, and hazard ratio = 1.04 [1.01-1.18] in women, P = 0.001). Persistent obesity was associated with a higher risk of incidence of colorectal cancer.

Association between fatty liver index and risk of end-stage renal disease stratified by kidney function in patients with type 2 diabetes: A nationwide population-based study.

OBJECTIVE: The effects of nonalcoholic fatty liver disease on the risk of end-stage renal disease (ESRD) remain unclear. We investigated the association between the fatty liver index (FLI) and risk of ESRD in patients with type 2 diabetes. METHODS: This population-based observational cohort study enrolled patients with diabetes who underwent health screening between 2009 and 2012 and utilized data from the Korean National Health Insurance Services. The FLI functioned as a surrogate marker for the presence of hepatic steatosis. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate < 60 ml/min/1.73 m² calculated using the Modification of Diet in Renal Disease equation. We performed Cox proportional hazards regression. RESULTS: Incident ESRD developed in 19,476 of 1,900,598 patients with type 2 diabetes during a median follow-up of 7.2 years. After adjusting for conventional risk factors, patients with high FLI scores had a higher risk for ESRD: FLI, 30-59 [hazard ratio (HR) = 1.124; 95% confidence interval (CI), 1.083-1.166]; FLI ≥ 60 [HR = 1.278; 95% CI, 1.217-1.343] compared with those with FLI < 30. The association between a high FLI score (≥ 60) and incident ESRD was more prominent in women than in men (male, FLI ≥60: HR, 1.106; 95% CI = 1.041-1.176 and female, FLI ≥ 60: HR, 1.835; 95% CI = 1.689-1.995). The association between a high FLI score (≥ 60) and the risk of ESRD differed according to baseline kidney function. High FLI scores increased the risk of ESRD (HR = 1.268; 95% CI, 1.198-1.342) in patients with CKD at baseline. CONCLUSION: High FLI scores are associated with a greater risk of ESRD in patients with type 2 diabetes with CKD at baseline. Close monitoring and appropriate management of hepatic steatosis may aid in preventing the progression of kidney dysfunction in patients with type 2 diabetes and CKD.

Alcohol consumption and the risk of new-onset uterine leiomyomas: a nationwide population-based study in 2.5 million Korean women aged 20 to 39 years.

BACKGROUND: Uterine leiomyomas are the most common benign tumors in women of childbearing age. Although there are several studies reporting the positive association of drinking alcohol with the incidence of uterine leiomyomas, studies targeting Korean women are lacking. OBJECTIVE: This study aimed to investigate the association between alcohol consumption and the risk of new-onset uterine leiomyomas in Korean women of early reproductive-age. STUDY DESIGN: This was a retrospective nationwide population-based cohort study using the Korean National Health Insurance Service database. Participants comprised 2,512,384 asymptomatic Korean women aged 20 to 39 years who underwent a national health examination from 2009 to 2012. The follow-up period was from the date of the first national health examination to the date of diagnosis of new-onset uterine leiomyomas or December 2018 if no uterine leiomyomas were detected. The diagnosis of uterine leiomyomas required 2 outpatient records within a year or 1 inpatient record of International Classification of Diseases, Tenth Revision (ICD-10) codes of uterine leiomyomas (D25) in the Korean National Health Insurance Service. Exclusion criteria were previously diagnosed uterine leiomyomas during the screening period (January 2002 to the date of first health examination) or uterine leiomyoma diagnosis within 1 year of baseline examination. The associations of alcohol consumption, amount drunk per drinking session, and sustained drinking over time with the risk of new-onset uterine leiomyomas were investigated. RESULTS: Approximately 6.1% of women aged 20 to 39 years were diagnosed with uterine leiomyomas after an average of 4.3 years. Alcohol consumption was associated with an increased incidence of new-onset uterine leiomyomas of 12% to 16% (hazard ratio, 1.12; 95% confidence interval, 1.11-1.14 for mild-to-moderate drinkers; hazard ratio, 1.16; 95% confidence interval, 1.12-1.20 for heavy drinkers). Drinking ≥1 days per week was associated with increased risk of uterine leiomyomas (hazard ratio, 1.11; 95% confidence interval, 1.10-1.12 for drinking 1 day per week; hazard ratio, 1.15; 95% confidence interval, 1.12-1.17 for drinking ≥3 days per week), and the association increased proportionately to the amount of alcohol consumed per drinking session (hazard ratio, 1.17; 95% confidence interval, 1.15-1.19 for ≥7 glasses per drinking session). Women who also reported alcohol consumption in the questionnaire administered 2 years later (sustained drinkers) exhibited a 20% increased risk of new-onset uterine leiomyomas (hazard ratio, 1.20; 95% confidence interval, 1.17-1.22) compared with women who answered that they did not drink alcohol at both times (sustained nondrinkers). In women who discontinued drinking, the risk was 3% (hazard ratio, 1.03; 95% confidence interval, 1.01-1.06), whereas in women who became drinkers, the risk was 14% (hazard ratio, 1.14; 95% confidence interval, 1.11-1.16). CONCLUSION: Having an alcohol drinking habit, the amount of alcohol consumed per drinking session, and sustained drinking over 2 years were significantly associated with the risk of new-onset uterine leiomyomas. Avoiding or discontinuing drinking could lower the risk of new-onset uterine leiomyomas in early reproductive-age women.

Efficacy of oral sulfate tablets for bowel preparation and adenoma detection rate.

BACKGROUND AND AIM: The adenoma detection rate (ADR), which is closely related to bowel preparation, is the most important factor for colonoscopy quality assessment. New oral sulfate tablets (OSTs) have been developed to improve bowel preparation compliance. This study evaluated the efficacy of OSTs in terms of the ADR and bowel preparation status. METHODS: Medical records of subjects under the age of 65 who underwent colonoscopy from March 2019 to February 2021 were retrospectively reviewed. Polyethylene glycol with ascorbic acid (PEG-A) was used as a bowel preparation for the first half of the study period, and OSTs were used for the second half. In total, 16 971 subjects were included in the study: 9199 (54.2%) used PEG-A, and 7772 (45.8%) used OSTs. Bowel cleansing quality was assessed by the Boston Bowel Preparation Scale (BBPS). RESULTS: The average age was 50 years. The rate of adequate bowel preparation was higher in the OST group than in the PEG-A group (97.2% vs 95.0%, P < 0.001). The mean BBPS was also higher in the OST group (8.02 vs 7.75, P < 0.001). The adenomas per colonoscopy (APC), the ADR and the sessile serrated polyp detection rate (SSPDR) were higher in the OST group than in the PEG-A group (APC 0.56 ± 1.01 vs 0.48 ± 0.91, P < 0.001; ADR 34.5% vs 30.7%, P < 0.001; SSPDR 5.2% vs 3.3%, P < 0.001). CONCLUSIONS: Compared with PEG-A, OSTs yielded superior APC, ADRs, SSPDRs, and better bowel cleanliness. Therefore, OSTs are a good alternative for patients who have difficulty taking large-volume bowel preparation formulations.

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.

Combined Effects of Chronic Kidney Disease and Nonalcoholic Fatty Liver Disease on the Risk of Cardiovascular Disease in Patients with Diabetes.

BACKGROUND: We investigated the combined effect of chronic kidney disease (CKD) and nonalcoholic fatty liver disease (NAFLD) on the risk of cardiovascular disease (CVD) in patients with type 2 diabetes. METHODS: Data were obtained from the Korean National Health Insurance Service. Patients with diabetes who participated in health screenings from 2009 to 2011 were included. The fatty liver index (FLI) was used as a surrogate marker for NAFLD. RESULTS: During a mean follow-up of 6.9 years, 40,863 incidents of myocardial infarction (MI), 58,427 strokes, and 116,977 deaths were reported in 1,607,232 patients with type 2 diabetes. After adjusting for conventional risk factors, patients with CKD and NAFLD showed the highest risk of MI and stroke (hazard ratio (HR) = 1.49; 95% confidence interval (CI): 1.42-1.57 and stroke, HR = 1.48; 95% CI: 1.41-1.54, respectively) compared with those without either CKD or NAFLD. Both overall and cardiovascular mortality were highest in the CKD/NAFLD group compared with other groups (HR = 2.00; 95% CI: 1.94-2.06, and HR = 2.20; 95% CI: 2.07-2.35, respectively). Advanced liver fibrosis was significantly associated with an increased risk of CVD in patients with NAFLD. Proteinuria was significantly associated with incidence of CVD events in patients with CKD. CONCLUSIONS: The combination of CKD and NAFLD was associated with an increased risk of CVD and mortality in patients with type 2 diabetes. Close monitoring and appropriate management of CKD and NAFLD may be warranted to prevent CVD in these patients.

Non-alcoholic/Metabolic-Associated Fatty Liver Disease and Helicobacter pylori Additively Increase the Risk of Arterial Stiffness.

Background: Non-alcoholic fatty liver disease (NAFLD) and Helicobacter pylori (Hp) infection have a close association with an increased risk of cardiovascular disease. Metabolic dysfunction-associated fatty liver disease (MAFLD) is characterized by metabolic dysfunction in NAFLD. We investigated the synergistic effects of NAFLD/MAFLD and Hp infection on the risk of arterial stiffness in an asymptomatic population. Methods: We included individuals who underwent abdominal ultrasonography, anti-Hp IgG antibody evaluations and cardio-ankle vascular index (CAVI) during health screening tests between January 2013 and December 2017. Arterial stiffness was defined using CAVI. A logistic regression model was used to analyze the independent and synergistic effects of NAFLD/MAFLD and Hp infection on the risk of arterial stiffness. Results: Among 3,195 subjects (mean age 54.7 years, 68.5% male), the prevalence of increased arterial stiffness was 36.4%. In the multivariate analysis, subjects with NAFLD but without Hp infection and those with both NAFLD and Hp infection had a significantly higher risk of increased arterial stiffness [odds ratio (OR) 1.61, 95% confidence interval (CI) 1.15-2.26, and OR 2.23, 95% CI 1.63-3.06, respectively], than subjects without Hp infection and NAFLD. Regarding MAFLD, Hp infection additively increased the risk of arterial stiffness in subjects with MAFLD (OR 2.13, 95% CI 1.64-2.78). Conclusions: An interactive effect of Hp infection on the risk of arterial stiffness in individuals with NAFLD/MAFLD was observed. Hp infection additively increases the risk of arterial stiffness in subjects with NAFLD or 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.

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.

Risk Factors for High-Risk Adenoma on the First Lifetime Colonoscopy Using Decision Tree Method: A Cross-Sectional Study in 6,047 Asymptomatic Koreans.

Background/Aims: As risk of colorectal neoplasm is varied even in persons with "average-risk," risk evaluation and tailored screening are needed. This study aimed to evaluate the risk factors of high-risk adenoma (HRA) in healthy individuals and determine the characteristics of advanced neoplasia (AN) among individual polyps. Methods: Asymptomatic adults who underwent the first lifetime screening colonoscopy at the Seoul National University Hospital Healthcare System Gangnam Center (SNUH GC) were recruited from 2004 to 2007 as SNUH GC Cohort and were followed for 10 years. Demographic and clinical characteristics were compared between the subjects with and without AN (≥10 mm in size, villous component, and/or high-grade dysplasia and/or cancer) or HRA (AN and/or 3 or more adenomas). For individual polyps, correlations between clinical or endoscopic features and histologic grades were evaluated using a decision tree method. Results: A total of 6,047 subjects were included and 5,621 polyps were found in 2,604 (43%) subjects. Advanced age, male sex, and current smoking status were statistically significant with regards to AN and HRA. A lower incidence of AN was observed in subjects taking aspirin. In the decision tree model, the location, shape, and size of the polyp, and sex of the subject were key predictors of the pathologic type. A weak but significant association was observed between the prediction of the final tree and the histological grouping (Kendall's tau-c = 0.142, p < 0001). Conclusions: Advanced neoplasia and HRA can be predicted using several individual characteristics and decision tree models.

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.

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.

Sarcopenic Obesity Is Significantly Associated With Coronary Artery Calcification.

Background: An association between sarcopenic obesity and cardiovascular disease has been suggested. We investigated the relationship between sarcopenia and coronary atherosclerosis, taking into account the presence or absence of obesity in a health check-up population. Methods: Data were reviewed for subjects who underwent bioelectrical impedance analysis (BIA) and coronary calcium scoring (CAC) computed tomography between January 2017 and December 2018. Appendicular skeletal muscle mass (ASM) was assessed using BIA. Sarcopenia was defined as reduction of muscle mass and calculated as ASM% (ASM/body weight) more than two standard deviations below the sex-specific mean for healthy young adults. CAC scores were dichotomized as low (<100) or high (≥100). Results: Among 1,282 subjects (mean age, 58.1 years; 75.5% male), the prevalence of high CAC was 21%. When the study population was divided into four groups according to their obesity and sarcopenia status, the prevalence of high CAC in the sarcopenic-obesity (SO) group was significantly higher than in the other groups (40.7%, P < 0.001). After adjusting for age, sex, hypertension, diabetes, dyslipidemia, and creatinine, subjects with SO exhibited a significantly higher odds of a high CAC score, compared with the non-sarcopenic, non-obese group (odds ratio, 1.92; 95% confidence interval, 1.16-3.18, P = 0.011). Conclusion: SO was significantly associated with CAC, independent of known risk factors for coronary artery disease. These findings suggest that sarcopenia and obesity may potentiate each other to increase atherosclerotic burden in coronary arteries, which may eventually lead to adverse cardiovascular events.

Increasing changes in visceral adiposity is associated with higher risk for colorectal adenoma: Multilevel analysis in a prospective cohort.

BACKGROUND AND AIM: While many studies demonstrated an association between visceral adiposity and colorectal adenoma (CRA), the effect of longitudinal changes in body fat composition on CRA is unclear. We investigated the longitudinal association between changes in visceral adiposity and CRA occurrence. METHODS: Between 2006 and 2018, 732 (62.8%) of the 1165 subjects in a prospective cohort voluntarily underwent follow-up abdominal fat computed tomography and colonoscopy. We defined incident and recurrent CRA as adenoma detected at follow-up colonoscopy from negative and positive adenoma at baseline colonoscopy, respectively. Multilevel survival analysis examined the longitudinal association between changes in visceral fat and CRA. RESULTS: During a median follow-up of 7.4 years, 400 (54.6%) subjects developed CRA. In multivariable analysis, increasing changes in visceral adipose tissue (VAT) area were associated with higher risk of incident adenoma (hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.00-1.46 for change per 10 cm2 increase; HR 1.79, 95% CI 1.08-2.97 for highest vs lowest quartile, P values for trend = 0.045). Likewise, increasing changes in VAT area were independently associated with a higher risk of recurrent adenoma (HR 1.35, 95% CI 1.13-1.62 for change per 10 cm2 increase; HR 1.62, 95% CI 1.04-2.52 for highest vs lowest quartile, P values for trend = 0.001). Changes in subcutaneous adipose tissue area were not independently associated with CRA. CONCLUSION: Increasing changes in VAT area were longitudinally associated with a higher risk of incident and recurrent CRA, independent of risk factors, suggesting that visceral adiposity may be an important target in CRA prevention.