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Background: The association between nonalcoholic fatty liver disease (NAFLD) and atrial fibrillation (AF) has been inconsistent, and the impact of hepatic fibrosis on this relationship remains uncertain. We investigated the association between NAFLD and the risk of new-onset AF across different age groups. Methods: A total of 3,179,582 participants from the 2009 Korean National Health Screening Program were divided into five groups based on NAFLD status: no NAFLD (fatty liver index [FLI] < 30); grade 1 NAFLD without advanced fibrosis (FLI 30–59 & BARD < 2); grade 1 NAFLD with advanced fibrosis (FLI 30–59 & BARD ≥ 2); grade 2 NAFLD without advanced fibrosis (FLI ≥ 60 & BARD < 2); and grade 2 NAFLD with advanced fibrosis (FLI ≥ 60 & BARD ≥ 2). The primary outcome was incident AF. Results: During the median follow-up of 9.3 years, 62,542 patients were diagnosed with new-onset AF. In the age- and sex-adjusted model, the risk of new-onset AF increased across NAFLD grades and fibrosis categories: grade 1 NAFLD without advanced fibrosis (hazard ratio [HR] 1.120, 95% confidence interval [CI]: 1.081–1.161); grade 1 NAFLD with advanced fibrosis (HR 1.275, 95% CI 1.251–1.300); grade 2 NAFLD without advanced fibrosis (HR 1.305, 95% CI: 1.252–1.360); and grade 2 NAFLD with advanced fibrosis (HR 1.627, 95% CI: 1.586–1.670). In the multivariate model, the excess risk of AF in patients with NAFLD and advanced fibrosis remained significant, even in participants aged 20–39 years. Conclusion: Patients with NAFLD had a higher risk of new-onset AF, which increased progressively with NAFLD severity, particularly in those aged 20–29 years. [ABSTRACT FROM AUTHOR]

Background: There exists a paucity of data regarding whether gamma‐glutamyl transferase is associated with disease‐specific mortality in patients with type 2 diabetes mellitus. This study aimed to investigate the association of serum gamma‐glutamyl transferase levels with all‐cause and disease‐specific mortality in patients with diabetes mellitus using a Korean nationwide health‐screening database. Methods: A total of 9 687 066 patients without viral hepatitis or liver cirrhosis who underwent health examination in 2009 were included. These patients were divided into four groups according to sex‐specific quartiles of serum gamma‐glutamyl transferase levels. Results: During a median follow‐up period of 8.1 years, 222 242 deaths were identified. The all‐cause mortality rate increased as the serum gamma‐glutamyl transferase levels became higher (highest quartile vs lowest quartile: hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.55–1.59; p for trend <.001). Similar trends were observed for cardiovascular disease (HR, 1.57; 95% CI, 1.53–1.62), ischemic heart disease (HR, 1.40; 95% CI, 1.33–1.48), and stroke (HR, 1.72; 95% CI, 1.60–1.85) in the highest quartile, as compared with the lowest quartile (p for trend <.001). As the gamma‐glutamyl transferase quartiles became higher, mortality rates related to cancer (HR, 1.56; 95% CI, 1.52–1.60), liver disease (HR, 9.42; 95% CI, 8.81–10.07), respiratory disease (HR, 1.55; 95% CI, 1.49–1.62), and infectious disease (HR, 1.73; 95% CI, 1.59–1.87) also increased in the highest quartile, compared with the lowest quartile (p for trend <.001). Conclusions: Serum gamma‐glutamyl transferase levels may be useful for the risk assessment of all‐cause and disease‐specific mortality among patients with type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background: Alcohol and diabetes are known risk factors for hepatocellular carcinoma (HCC); however, it is unclear whether the association between alcohol consumption and HCC risk differs by fasting serum glucose level and diabetes. We investigated the dose–response relationship between alcohol consumption and the risk of HCC according to glycemic status. Methods and findings: This population-based observational cohort study included patients who underwent general health checkups in 2009 using the Korean National Health Insurance Service Database. The primary outcome was HCC incidence, and Cox proportional hazard regression analysis was performed to estimate the relationship between alcohol consumption and HCC risk according to glycemic status. A total of 34,321 patients newly diagnosed with HCC were observed in the median follow-up period of 8.3 years. In the multivariable model, we adjusted for age, sex, smoking, regular exercise, income, hypertension, dyslipidemia, and body mass index. Mild-to-moderate alcohol consumption increased the risk of HCC in all glycemic statuses (normoglycemia: hazard ratio [HR], 1.06; 95% confidence interval [CI], 1.02 to 1.10; prediabetes: HR, 1.19; 95% CI, 1.14 to 1.24; and diabetes: HR, 2.02; 95% CI, 1.93 to 2.11) compared to normoglycemic nondrinking. Heavy alcohol consumption also increased the risk of HCC in all glycemic statuses (normoglycemia: HR, 1.39; 95% CI, 1.32 to 1.46; prediabetes: HR, 1.67; 95% CI, 1.58 to 1.77; and diabetes: HR, 3.29; 95% CI, 3.11 to 3.49) compared to normoglycemic nondrinking. Since alcohol consumption information in this study was based on a self-administered questionnaire, there may be a possibility of underestimation. Although we excluded patients with a history of viral hepatitis using diagnosis codes, we could not obtain information on hepatitis B or hepatitis C serum markers. Conclusions: Both mild-to-moderate and heavy alcohol consumption was associated with an increased risk of HCC in all glycemic statuses. The increased risk of HCC according to alcohol consumption was the highest in the diabetes group, suggesting that more intensive alcohol abstinence is required for patients with diabetes. In a large population based cohort study including more than 34,000 people in Korea, Eun Ju Cho and Goh Eun Chung investigate the impact of alcohol consumption on the development of hepatocellular carcinoma according to fasting serum glucose level. Author summary: Why was this study done?: Alcohol and diabetes are known risk factors for hepatocellular carcinoma (HCC). It is unclear whether the association between alcohol consumption and HCC risk differs by fasting serum glucose level and diabetes. What did the researchers do and find?: We analyzed the health checkup data of the Korean population aged 20 years or older in 2009 provided by the Korean National Health Insurance Service. Multivariable Cox proportional hazards regression models were used to evaluate the association of alcohol consumption with the risk of HCC, with a median follow-up duration of 8.3 years. In this study, the risk of HCC increased linearly with alcohol consumption in a dose-dependent manner according to glycemic status with synergistic effects between prediabetes/diabetes and alcohol. Any amount or frequency of alcohol consumption increased the risk of HCC in patients with diabetes or prediabetes status. What do these findings mean?: The increased risk of HCC according to alcohol consumption was the highest in the diabetes group, suggesting that more intensive alcohol abstinence is required for patients with diabetes. The interpretation of these results is limited due to potential underestimation of alcohol consumption as the information on alcohol consumption obtained in this study was based on a self-administered questionnaire. [ABSTRACT FROM AUTHOR]

Although the association of nonalcoholic fatty liver disease (NAFLD) with obesity or sarcopenia is known, few studies have investigated the combined effect of various body composition parameters on the risk of NAFLD. Thus, the aim of this study was to evaluate effects of interactions between various body composition parameters, including obesity, visceral adiposity, and sarcopenia, on NAFLD. Data of subjects who underwent health checkups between 2010 and December 2020 were retrospectively analyzed. Body composition parameters including appendicular skeletal muscle mass (ASM) and visceral adiposity were assessed using bioelectrical impedance analysis. Sarcopenia was defined as ASM/weight beyond two standard deviations below the gender-specific mean for healthy young adults. NAFLD was diagnosed using hepatic ultrasonography. Interaction analyses, including relative excess risk due to interaction (RERI), synergy index (SI), and attributable proportion due to interaction (AP), were performed. Among a total of 17,540 subjects (mean age: 46.7 years, 49.4% males), the prevalence of NAFLD was 35.9%. The odds ratio (OR) of interaction between obesity and visceral adiposity affecting NAFLD was 9.14 (95% CI: 8.29–10.07). The RERI was 2.63 (95% CI: 1.71–3.55), SI was 1.48 (95% CI: 1.29–1.69) and AP was 29%. The OR of interaction between obesity and sarcopenia affecting NAFLD was 8.46 (95% CI: 7.01–10.21). The RERI was 2.21 (95% CI: 0.51–3.90). SI was 1.42(95% CI: 1.11–1.82) and AP was 26%. The OR of interaction between sarcopenia and visceral adiposity affecting NAFLD was 7.25 (95% CI: 6.04–8.71), however, there was no significant additive interaction with RERI = 0.87 (95% CI: −0.76 to 2.51). Obesity, visceral adiposity, and sarcopenia were found to be positively associated with NAFLD. Obesity, visceral adiposity, and sarcopenia were found to have additive interaction effects on NAFLD. [ABSTRACT FROM AUTHOR]

Background: Metabolic-associated fatty liver disease (MAFLD) encompasses diverse disease groups with potentially heterogeneous clinical outcomes. We investigated the risk of all-cause and disease-specific mortality in MAFLD subgroups. Methods: Using the Korean National Health Insurance Service database, participants were divided into four subgroups: no MAFLD, MAFLD-diabetes, MAFLD-overweight/obese, and MAFLD-lean. Hazard ratios (HRs) and 95% confidence interval (CI) values for all-cause and disease-specific mortality according to MAFLD subgroups were analyzed using Cox proportional hazards models. Results: Among 9,935,314 participants, those with MAFLD-diabetes showed the highest risk of all-cause and disease-specific mortality. The HRs (95% CI) for all-cause mortality were 1.61 (1.59–1.63), 1.36 (1.34–1.38), and 1.19 (1.18–1.20) in the MAFLD-diabetes, MAFLD-lean, and MAFLD-overweight/obese groups, respectively. The magnitude of cardiovascular disease and cancer-related risk showed the same pattern. The risk of liver-related mortality in the MAFLD-lean group (HR: 2.84, 95% CI: 2.72–2.97) was comparable with that in the MAFLD-diabetes group (HR: 2.85, 95% CI: 2.75–2.95). When stratified by body mass index, liver-related mortality was the highest in MAFLD-lean individuals in the underweight group (HR, 5.03, 95% CI: 4.23–5.97). Conclusions: The MAFLD-lean and MAFLD-diabetes groups had a higher risk of all-cause and disease-specific mortality than did the MAFLD-overweight/obese group. Classifying MAFLD subgroups based on metabolic phenotypes might help risk stratification of patients with MAFLD. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) commonly coexist. However, NAFLD's effect on mortality in Asian patients with type 2 diabetes awaits full elucidation. Therefore, we examined NAFLD-related all-cause and cause-specific mortality in a nationwide Asian population with type 2 diabetes. Methods: We included patients who had undergone general health checkups between 2009 and 2012 using the National Health Insurance Service database linked to death-certificate data. Hepatic steatosis was defined as a fatty liver index (FLI) ≥ 60, and advanced hepatic fibrosis was determined using the BARD score. Findings: During the follow-up period of 8.1 years, 222,242 deaths occurred, with a mortality rate of 14.3/1000 person-years. An FLI ≥ 60 was significantly associated with increased risks of all-cause and cause-specific mortality including cardiovascular disease (CVD)-, cancer-, and liver disease (FLI ≥ 60: hazard ratio [HR] = 1.02, 95% confidence interval [CI] 1.01–1.03 for all-cause; 1.07, 1.04–1.10 for CVD; 1.12, 1.09–1.14 for cancer; and 2.63, 2.50–2.77 for liver disease). Those with an FLI ≥ 60 and fibrosis (BARD ≥ 2) exhibited increased risks of all-cause (HR, 95% CI 1.11, 1.10–1.12), CVD- (HR, 95% CI 1.11, 1.09–1.14), cancer- (HR, 95% CI 1.17, 1.15–1.19), and liver disease-related (HR, 95% CI 2.38, 2.29–2.49) mortality. Conclusion: Hepatic steatosis and advanced fibrosis were significantly associated with risks of overall and cause-specific mortality in patients with type 2 diabetes. Our results provide evidence that determining the presence of hepatic steatosis and/or fibrosis potentially plays a role in risk stratification of mortality outcomes in patients with type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) infection remains a threat to global public health. Serum hepatitis B surface antigen (HBsAg) has been used in screening for HBV infection. Quantitative HBsAg assays are useful for monitoring the natural history of HBV infection and its response to therapy. The aim of this study was to determine the relationship between quantitative (qHBsAg; IU/mL) and semi-quantitative (sqHBsAg; signal-to-cutoff ratio [S/Co]) HBsAg titers in patients with chronic hepatitis B (CHB). Methods: We retrospectively included 284 samples with HBV DNA < 20 IU/mL from patients who had simultaneous qHBsAg (using electrochemiluminescence assay) and sqHBsAg tests. Patients were grouped according to their serum HBV-envelope antigen (HBeAg) status (HBeAg-negative, n = 239 and HBeAg-positive, n = 45). The Spearman test was used to analyze the correlation between the quantitative and semi-quantitative assays. Results: There was a significant linear correlation between sqHBsAg and qHBsAg in the HBeAg-negative patients (qHBsAg [IU/mL] = 0.0094 × sqHBsAg [S/Co]1.323; adjusted R2 = 0.8445; p < 0.001). There was a substantial hook effect in the assays from the HBeAg-positive patients, so we performed a stratified analysis according to qHBsAg <1000 IU/mL or ≥1000 IU/mL and found a significant positive linear correlation between sqHBsAg S/Co and qHBsAg (qHBsAg [IU/mL] = 0.072 × sqHBsAg [S/Co]1.331; adjusted R2 = 0.7878; p < 0.001) in HBeAg-positive patients with qHBsAg titers of <1000 IU/mL and a significant negative correlation in HBeAg-positive patients with qHBsAg titers of ≥1000 IU/mL (qHBsAg [IU/mL] = 8.987 × 1014 × sqHBsAg [S/Co]−3.175; adjusted R2 = 0.6350; p < 0.001). Conclusions: There was a highly linear, positive correlation between qHBsAg and sqHBsAg in HBeAg-negative CHB patients. The hook effect led to a negative correlation in HBeAg-positive CHB patients with qHBsAg titers ≥1000 IU/mL. [ABSTRACT FROM AUTHOR]

Aim: To investigate the relationship between nonalcoholic fatty liver disease (NAFLD) and cardiovascular events among a nationally representative sample of young adults in Korea. Methods and Results: This population‐based cohort study from the Korean National Health Insurance Service included adults who were aged 20 to 39 years when they underwent a health examination between 2009 and 2012. NAFLD was defined as a fatty liver index (FLI) ≥60, and participants were divided into three groups according to FLI (<30, 30‐59 and ≥60) to investigate the dose‐dependent effect of FLI score. Among 5 324 410 participants, 9.8% had an FLI ≥60. There were 13 051 myocardial infarctions (MIs; 0.39%) and 8573 strokes (0.26%) during a median follow‐up of 8.4 years. In multivariable analysis, NAFLD was associated with a higher risk of MI and stroke (hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.61‐1.77 and HR 1.73, 95% CI 1.63‐1.84, respectively). MI and stroke had dose‐dependent relationships with FLI (HR 1.28 in participants with FLI 30‐59 and 1.73 in those with FLI ≥60 for MI and HR 1.18 in participants with FLI 30‐59 and 1.41 in those with FLI ≥60 for stroke, respectively). Conclusions: Nonalcoholic fatty liver disease was an independent predictor of MI and stroke in young adults. These results suggest that primary prevention of cardiovascular disease should be emphasized in young adults with NAFLD. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that obstructive sleep apnea (OSA) is a metabolic syndrome-related disease; however, the association between nonalcoholic fatty liver disease (NAFLD) and OSA is not firmly established. In this study, we investigated the relationship between NAFLD and OSA in a general population drawn from a nationwide population-based cohort. Data from the Korean National Health Insurance System between January 2009 and December 2009 were analyzed using Cox proportional hazards model. NAFLD was defined as a fatty liver index (FLI) ≥ 60 in patients without excessive alcohol consumption (who were excluded from the study). Newly diagnosed OSA during follow-up was identified using claims data. Among the 8,116,524 participants, 22.6% had an FLI score of 30–60 and 11.5% had an FLI ≥ 60. During median follow-up of 6.3 years, 45,143 cases of incident OSA occurred. In multivariable analysis, the risk of OSA was significantly higher in the higher FLI groups (adjusted hazard ratio [aHR] 1.15, 95% confidence interval [CI] 1.12–1.18 for FLI 30–60 and aHR 1.21, 95% CI 1.17–1.26 for FLI ≥ 60). These findings were consistent regardless of body mass index and presence of abdominal obesity. In conclusion, a high FLI score may help identify individuals with a high risk of OSA. Understanding the association between NAFLD and OSA may have clinical implications for risk-stratification of individuals with NAFLD. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most common arrhythmia in the elderly. Arterial stiffness may predict the risk of AF, but this relationship has not been fully evaluated. We assessed the association between arterial stiffness and prevalent AF. All subjects who had electrocardiography performed and a cardio-ankle vascular index (CAVI) calculated during a screening examination between 2010 and 2019 were enrolled. To evaluate the association between increased arterial stiffness and AF, we divided the population according to their Framingham risk score (FRS) into low-, intermediate-, and high-risk groups. A total of 8048 subjects were evaluated. The multivariate analysis revealed that increased arterial stiffness was significantly associated with AF prevalence, even after adjusting cardiovascular risk factors [odds ratio (OR) 1.685, 95% confidence interval (CI) 1.908–2.588, p = 0.017]. When we subcategorized the subjects according to their FRS, increased arterial stiffness was significantly associated with AF in the intermediate- and high-risk groups (OR 3.062, 95% CI 1.39-6.740 and OR3.877, 95% CI 1.142-13.167, respectively, BMI adjusted. High arterial stiffness shows a significant association with AF in those with intermediate or high cardiovascular risk, and can be used for further risk stratification of patients. [ABSTRACT FROM AUTHOR]

Background: Studies on association between fatty liver disease and overall mortality have yielded conflicting results. We evaluated the impact of fatty liver disease and advanced fibrosis on overall morality with a focus on body size and abdominal fat distribution measured by computed tomography. Methods: We performed a prospective cohort study including 34 080 subjects (mean age, 51.4 years; 58.6% men) who underwent abdominal ultrasonography and fat computed tomography, from 2007 to 2015. Fatty liver was diagnosed by ultrasonography, and advanced fibrosis was defined as high probability of advanced fibrosis based on three noninvasive methods, aspartate aminotransferase‐to‐platelet ratio index, non‐alcoholic fatty liver disease fibrosis score, and fibrosis‐4 score. Body size was categorized by body mass index into obese (≥ 25 kg/m2) or nonobese (< 25 kg/m2). Multivariate proportional Cox hazard regression analyses were performed. Results: The prevalence of fatty liver disease was 37.5%, while the prevalence of advanced fibrosis in fatty liver disease was 1.8%. During a median follow‐up of 87 months (interquartile range, 62–110), 296 deaths occurred. Fatty liver disease was not associated with higher overall mortality (multivariate‐adjusted hazard ratio [HR] 1.02, 95% confidence interval [CI] 0.77–1.34), while increased subcutaneous adiposity was associated with decreased mortality (HR 0.72, 95% CI 0.60–0.88). Advanced fibrosis resulted in a 3.5‐fold increase in overall mortality (adjusted HR 3.52, 95% CI 1.86–6.65), which was more pronounced in the nonobese. Conclusions: While fatty liver disease did not impact overall mortality, subcutaneous adiposity was associated with reduced overall mortality. Advanced fibrosis was an independent predictor of increase in overall mortality. [ABSTRACT FROM AUTHOR]

The coexistence of HBsAg and anti-HBs has been reported in some chronic hepatitis B patients; however, the long-term outcomes of this serological profile have not been elucidated. We aimed to evaluate the long-term outcomes of HBsAg/anti-HBs double-positive chronic hepatitis B patients. Chronic hepatitis B patients who underwent baseline abdominal ultrasonography and follow-up (HBsAg/anti-HBs assessment and abdominal ultrasonography) at our healthcare center were included. The "coexistence group" included patients positive for both HBsAg and anti-HBs and the "control group" included patients positive for only HBsAg during follow-up. The outcomes were hepatocellular carcinoma (HCC) incidence, HBsAg seroclearance and overall mortality. Kaplan-Meier and Cox proportional hazard regression analyses were performed. Of the 2,341 eligible patients, 166 (7.1%) were in the coexistence group. The total follow-up duration was 5.4 years. The coexistence group had a 3.08-fold higher risk of HCC than the control group [hazard ratio (HR) 3.08, 95% confidence interval(CI) 1.26–7.55, P = 0.014] in multivariate analysis. The coexistence group had more HBsAg seroclearance than the control group (HR 1.43, 95% CI 1.01–2.03, P = 0.046). However, overall mortality did not significantly differ between the 2 groups. The coexistence group is heterogeneous and includes subjects with unfavorable outcomes (incidence of HCC) and favorable outcomes (more HBsAg seroclearance). [ABSTRACT FROM AUTHOR]

Background. Helicobacter pylori (HP) and gastric atrophy are risk factors for gastric cancer. We evaluated whether the combination of serum HP antibody and pepsinogen (PG), which is indicative of gastric atrophy, could serve as a predictive marker for the development of gastric neoplasms in a Korean population. Methods. The subjects who had undergone health-screening examination with endoscopic follow-ups were classified into the following 4 groups according to serum PG status and HP antibody at baseline: group A (HP (−), normal PG), group B (HP (+), normal PG), group C (HP (+), atrophic PG), and group D (HP (−), atrophic PG). We compared the development of gastric neoplasms among the groups. Results. Of the 3297 subjects, 1239 (37.6%) were categorized as group A, 1484 (45.0%) as group B, 536 (16.3%) as group C, and 38 (1.2%) as group D. During the 5.6 years of mean follow-up period, the annual incidence of gastric neoplasms increased gradually by 0.06% in group A, 0.16% in group B, 0.38% in group C, and 0.49% in group D. A Cox proportional hazard model showed increased development of gastric neoplasms according to group (P for trend = 0.025). Compared to group A, the hazard ratio was 8.25 for group D (95% confidence interval 0.2–74.24), 5.35 for group C (1.68–17.05), and 2.65 for group B (0.86–8.14). Conclusion. The combination of serum PG and HP antibody is useful for predicting the development of gastric neoplasms, including cancer and adenoma, in a Korean population using endoscopic surveillance. [ABSTRACT FROM AUTHOR]

Background and aims Nonalcoholic fatty liver disease (NAFLD) may be associated with a wide spectrum of cardiac abnormalities, which share many metabolic risk factors. This study aimed to evaluate whether NAFLD is associated with left ventricular (LV) diastolic dysfunction independent of other classical risk factors. Methods A total of 3300 subjects (mean age, 54.1 years; 62.9% men), who underwent echocardiography and hepatic ultrasonography, were enrolled. LV diastolic dysfunction was diagnosed and graded using conventional and Doppler echocardiographic assessments. NAFLD was diagnosed by ultrasonographic findings without any evidence of significant alcohol consumption or viral hepatitis, other liver diseases, or medication provoking fatty liver. Advanced fibrosis was defined as having intermediate-high probability for advanced fibrosis using the NAFLD fibrosis score. Results The prevalence of LV diastolic dysfunction was 35.1%. NAFLD had a higher prevalence and severity of LV diastolic dysfunction. The prevalence rates of LV diastolic dysfunction were significantly increased according to the NAFLD fibrosis grade (30.4% for no-NAFLD, 35.2% for NAFLD without advanced fibrosis and 57.4% for NAFLD with advanced fibrosis, p  < 0.001). Multivariable analysis showed that NAFLD was associated with a 29% increase in the risk of diastolic dysfunction compared with controls (odds ratio [OR] 1.29; 95% confidence interval [CI] 1.07–1.60). There was significant interaction between obesity (BMI < 25 kg/m 2 vs.  ≥ 25 kg/m 2 ) and advanced fibrosis for LV diastolic dysfunction. A significant, incrementally increased risk of diastolic dysfunction according to the fibrosis grade was more pronounced in the non-obese population [adjusted OR (95% CI), 1.40 (1.06–1.84) for NAFLD without advanced fibrosis, 1.44 (0.95–2.17) for NAFLD with advanced fibrosis vs. no NAFLD, P for trend = 0.022] compared with the obese population ( p for trend = 0.081), independent of other well-defined risk factors. Conclusions NAFLD was associated with increased risk for LV diastolic dysfunction. In addition, an incrementally increased risk for LV diastolic dysfunction according to fibrosis grade was prominent in the non-obese population. [ABSTRACT FROM AUTHOR]

Abstract: Background & Aims: Evaluation of the controlled attenuation parameter (CAP) is a promising noninvasive method for assessing hepatic steatosis. Despite the increasing reliability of the CAP for assessing steatosis in subjects with chronic liver disease, few studies have evaluated the CAP in asymptomatic subjects without overt liver disease. Therefore, we aimed to evaluate the usefulness of the CAP for a health check‐up population. Methods: We enrolled subjects who underwent abdominal ultrasonography (US), FibroScan (Echosens, France) and blood sampling during medical health check‐ups. The CAP was measured using FibroScan, and increased CAP was defined as CAP ≥ 222 dB/m. Results: A total of 1133 subjects were included; 589 subjects (52.0%) had fatty liver based on US, and 604 subjects (53.3%) had increased CAP. Increased CAP was significantly associated with metabolic abnormalities, including higher body mass index (BMI)[odds ratio (OR) = 1.33;95% confidence interval (CI),1.24‐1.43; P < .001], higher alanine aminotransferase (ALT) (OR = 1.02; 95% CI, 1.01‐1.04; P = .003), higher insulin (OR = 1.04; 95% CI, 1.00‐1.08; P = .037), higher triglyceride (OR = 1.00; 95% CI, 1.00‐1.01; P = 0.042) and older age (OR = 1.02; 95% CI, 1.00‐1.03; P = .05). Furthermore, a comparison of clinical parameters among three groups (normal vs no fatty liver by US but increased CAP vs fatty liver based on US) revealed that metabolic parameters, including blood pressure, BMI, waist circumference, aspartate aminotransferase (AST), ALT, triglycerides, fasting glucose, uric acid, insulin, homeostasis model assessment‐estimated insulin resistance and liver stiffness measurements, gradually increased across the three groups (all P < .001). Conclusions: In conclusion, increased CAP could be an early indicator of fatty liver disease with metabolic abnormalities that manifests even before a sonographic fatty change appears. [ABSTRACT FROM AUTHOR]

Aims. Chronic low-grade inflammation is thought to be associated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD). This study aimed to determine the association between serum white blood cell (WBC) counts and the development of incidental NAFLD. Methods. In this retrospective longitudinal cohort study, we recruited participants who underwent abdominal ultrasonography and blood samplings during medical checkups in both 2005 and 2010. A total of 2,216 subjects were included in our analyses. Results. The prevalence of NAFLD in 2010 increased steadily in conjunction with increasing WBC counts in 2005 after adjustment for body mass index (BMI) [odds ratio (OR) 2.44, 95% confidence interval (CI) = 1.49–4.00 for women and OR 2.42, 95% CI = 1.61–3.63 for men, lowest quartile versus highest quartile]. Multivariate regression analysis after adjusting for age, BMI, hypertension, smoking, triglycerides, HDL cholesterol, and glucose levels revealed that NAFLD was significantly associated with the highest WBC quartile compared to the lowest quartile [OR 1.85, 95% CI, 1.10−3.10 for women and OR 1.68, 95% CI, 1.08−2.61 for men]. Conclusions. We demonstrated that the risk of developing NAFLD was significantly associated with WBC counts independently of metabolic factors. This finding provides novel evidence indicating that serum WBC counts may be potential surrogate markers of NAFLD. [ABSTRACT FROM AUTHOR]

Recognizing anatomical sections during colonoscopy is crucial for diagnosing colonic diseases and generating accurate reports. While recent studies have endeavored to identify anatomical regions of the colon using deep learning, the deformable anatomical characteristics of the colon pose challenges for establishing a reliable localization system. This study presents a system utilizing 100 colonoscopy videos, combining density clustering and deep learning. Cascaded CNN models are employed to estimate the appendix orifice (AO), flexures, and "outside of the body," sequentially. Subsequently, DBSCAN algorithm is applied to identify anatomical sections. Clustering-based analysis integrates clinical knowledge and context based on the anatomical section within the model. We address challenges posed by colonoscopy images through non-informative removal preprocessing. The image data is labeled by clinicians, and the system deduces section correspondence stochastically. The model categorizes the colon into three sections: right (cecum and ascending colon), middle (transverse colon), and left (descending colon, sigmoid colon, rectum). We estimated the appearance time of anatomical boundaries with an average error of 6.31 s for AO, 9.79 s for HF, 27.69 s for SF, and 3.26 s for outside of the body. The proposed method can facilitate future advancements towards AI-based automatic reporting, offering time-saving efficacy and standardization. [ABSTRACT FROM AUTHOR]

Background/Aims. Women after menopause have increased insulin resistance and visceral fat, which may increase the prevalence of nonalcoholic fatty liver disease (NAFLD). However, the pathogenesis of NAFLD in women has not been clearly defined. In this study, we aimed to determine the risk factors for NAFLD in women. Methods. A retrospective cohort study was conducted. Women who underwent abdominal ultrasonography and blood sampling for routine health check-ups were recruited. Results. Among 1,423 subjects, 695 women (48.9%) were in a menopausal state. The prevalence of NAFLD was higher in postmenopausal women than in premenopausal women (27.2% versus 14.4%, P<0.001). In premenopausal women, low HDL-cholesterol, central obesity, and homeostasis model assessment-estimated insulin resistance showed a significant association with the increased risk of NAFLD in multivariate analysis. In postmenopausal women, the presence of diabetes, triglyceridemia, and central obesity showed a significant association with the risk of NAFLD. The presence of menopause and hormone replacement therapy in postmenopausal women were not risk factors for NAFLD. Conclusions. Our findings showed different metabolic factors for NAFLD in pre- and postmenopausal women. However, the key issues are the same: central obesity and insulin resistance. These results reemphasize the importance of metabolic factors irrespective of menopausal status in the pathogenesis of NAFLD in women. [ABSTRACT FROM AUTHOR]

Objective. Various factors including age, sex, body mass index (BMI) and history of operation have been linked to the colonoscopic intubation time. The aims of this study were to identify the factors predicting cecal intubation time (CIT) and to evaluate the effect of the visceral adipose tissue (VAT) area on CIT. Material and methods. A total of 1386 consecutive subjects who underwent colonoscopy and abdominal CT on the same day for a health checkup at a single health care center in Korea from August to December 2011 were studied prospectively. Age, sex, BMI, height, waist circumference, history of operation, symptoms of irritable bowel syndrome, bowel preparation status, experience of colonoscopists, VAT amount on abdominal CT and time required to reach the cecum were analyzed. Results. The mean age of the subjects was 53.0 ± 9.6 years, and 63.5% were male. The median CIT was 271 s. Univariate analyses showed that female gender, old age, shorter height, lower BMI, prior history of surgery and lower VAT were associated with longer CIT. To adjust for confounding effects of the gender, we investigated the genders separately in multivariate analysis. Older age and lower VAT were associated with prolonged CIT. However, the significance of association of VAT on prolonged CIT disappeared in women. Conclusion. This study demonstrates that CIT is prolonged by lower VAT area in men. This is the first study to demonstrate a direct association between VAT area and CIT. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background & Aims: The aim of this study was to characterize the relationship between the broad spectrum of hypothyroidism and NAFLD. Methods: A cross-sectional study with 4648 health check-up subjects (2324 cases with hypothyroidism vs. age- and sex-matched controls) was conducted. The subjects were categorized as having either subclinical [thyroid-stimulating hormone (TSH) ⩾4.1mIU/L and normal free thyroixine (T4) level (0.7–1.8ng/dl)] or overt hypothyroidism [free T4 <0.7ng/dl]. NAFLD was diagnosed on the basis of typical ultrasonographic findings, and alcohol consumption of less than 20g/day in the absence of other causes of liver disease. Results: The mean age of the subjects was 48.6±11.8years and 62.4% were female. NAFLD was significantly associated with hypothyroidism (30.2% patients vs. 19.5% control, p <0.001). The prevalence of NAFLD and abnormal liver enzyme levels (ALT>33/25IU/L) increased steadily with increasing grades of hypothyroidism (for NAFLD, subclinical: 29.9% and overt: 36.3%; for abnormal ALT, 20.1% and 25.9%, p <0.001, respectively). Multivariate regression analysis showed that NAFLD was statistically significantly associated with hypothyroidism (odds ratio (OR) 1.38, 95% confidence interval (CI), 1.17–1.62) and the grade of hypothyroidism in a dose-dependent manner (OR 1.36, 95% CI, 1.16–1.61 in subclinical hypothyroidism and OR 1.71, 95% CI, 1.10–2.66 in overt hypothyroidism). Conclusions: Subclinical hypothyroidism, even in the range of upper normal TSH levels, was found to be related to NAFLD in a dose-dependent manner. Hypothyroidism is closely associated with NAFLD independently of known metabolic risk factors, confirming a relevant clinical relationship between these two diseases. [Copyright &y& Elsevier]

Background and Aim: Patients with persistently active hepatitis B virus (HBV) replication are at high risk for progression to liver cirrhosis and hepatocellular carcinoma (HCC). The influence of the viral load of HBV on intrahepatic recurrence after local ablation therapy in patients with HBV-related HCC has not been elucidated. We aimed to evaluate predictors of intrahepatic recurrence and clarify the correlation between viral load and intrahepatic recurrence after percutaneous ablation. Methods: Patients with HBV-related, solitary HCC undergoing radiofrequency ablation (RFA) or percutaneous ethanol injection (PEI), between October 2004 and December 2008 were prospectively enrolled. Statistical analyses were performed using the Kaplan-Meier method and Cox regression model to identify risk factors for intrahepatic recurrence. Results: A total of 145 patients (male, 81.4%; mean age, 55.3 years) were included. Ninety patients (62.1%) had serum HBV DNA ≥ 2000 IU/mL. The median follow-up duration was 28.9 months (range, 12.0-57.0) and 63 patients (43.4%) experienced intrahepatic tumor recurrence. Multivariate analysis indicated that seropositivity for hepatitis B envelope antigen (HBeAg) was an independent negative predictor of intrahepatic recurrence (hazard ratio, 0.473; P = 0.026) and late (≥ 1 year) recurrence (HR, 0.288; P = 0.012). The serum alpha fetoprotein (AFP) level also significantly predicted late recurrence (HR, 1.001; P = 0.005). However, neither the ablation method nor serum HBV DNA titers were correlated with intrahepatic recurrence. Conclusions: These findings show that HBeAg-negativity and serum AFP levels were associated with late intrahepatic recurrence of HCC, implicating HBeAg-negativity as a risk factor for de novo recurrence after percutaneous ablation in HBV-related HCC. [ABSTRACT FROM AUTHOR]

Population-based data regarding the prognostic implication of gamma-glutamyl transferase (GGT) have been inconsistent. We examined the association of GGT with all-cause and disease-specific mortality. Using the Korean nationwide database, we included 9,687,066 subjects without viral hepatitis or cirrhosis who underwent a health examination in 2009. Subjects were classified into three groups by sex-specific tertile of serum GGT levels. The underlying causes of death were classified by 10th Revision of the International Classification of Diseases codes. During the median follow-up period of 8.3 years, 460,699 deaths were identified. All-cause mortality increased as serum GGT levels became higher (hazard ratio [HR], 95% confidence interval [CI] 1.05, 1.04–1.05 in the middle tertile, and 1.33, 1.32–1.34 in the high tertile) compared to the low tertile of serum GGT levels. Similar trends were observed for cardiovascular disease (CVD) (HR, 95% CI 1.07, 1.05–1.09 in the middle tertile, 1.29, 1.26–1.31 in the high tertile), cancer (HR, 95% CI 1.08, 1.07–1.10 in the middle tertile, 1.38, 1.36–1.39 in the high tertile), respiratory disease (HR, 95% CI 1.10, 1.08–1.13 in the middle tertile, 1.39, 1.35–1.43 in the high tertile), and liver disease mortality (HR, 95% CI 1.74, 1.66–1.83 in the middle tertile, 6.73, 6.46–7.01 in the high tertile). Regardless of smoking, alcohol consumption and history of previous CVD and cancer, a higher serum GGT levels were associated with a higher risk of mortality. Serum GGT levels may be useful for risk assessment of all-cause and disease-specific mortality in general population. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Several genetic variants are known to be associated with nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the longitudinal associations between genetic variants and NAFLD.Methods: We performed a genome-wide association study (GWAS) in Korean individuals who underwent repeated health check-ups. NAFLD was defined by ultrasonography and exclusion of secondary causes.Results: The subjects had a median age of 50.0 years, and 54.8% were male. The median follow-up duration was 39 months. Among the 3905 subjects without NAFLD at baseline, 874 (22.4%) subjects developed NAFLD, and among the 1818 subjects with NAFLD at baseline, NAFLD regressed in 336 (18.5%) subjects during the follow-up period. After adjusting for age, sex and body mass index, no single-nucleotide polymorphism (SNP) passed Bonferroni correction for genome-wide significance in the development or regression of NAFLD. Among the SNPs that passed the genome-wide suggestiveness threshold (p = 1E-04) in the discovery set in the GWAS, only 1 SNP (rs4906353) showed an association with the development of NAFLD, with marginal significance in the validation set (p-value, discovery set = 9.68E-5 and validation set = 0.00531).Conclusions: This exploratory study suggests that longitudinal changes in NAFLD are not associated with genetic variants in the Korean population. These findings provide new insight into genetic mechanisms in the pathogenesis of NAFLD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Although genetic features vary across ethnicities, few genome-wide association studies (GWAS) have reported the genetic determinants of liver enzyme expression. This study was aimed to evaluate the associations of genome-wide single nuclear polymorphisms (SNPs) with the liver enzymes in a Korean population. Methods: We performed a GWAS to identify genetic loci influencing liver function, as measured by concentrations of alkaline phosphatase (ALP), alanine transaminase (ALT), gamma-glutamyl transferase (GGT) and total bilirubin (BIL) in in Korean study participants. Results: A total of 6,488 subjects (4,457 in the discovery and 2,031 in the validation set) were included. The mean subject age was 50.0±10.6 years (male, 53.7%). Among a total of 546,738 SNPs tested, rs651007 and rs579459 located in the ABO gene showed strong associations with ALP (P = 1.63×10−8 and 5.61×10−8, respectively [discovery set]; P = 4.08×10−15 and 9.92×10−16, respectively [validation set]). Additionally, rs5751901 and rs2006092, which are located in the GGT1 gene, showed strong associations with GGT (P = 6.44×10−15 and 1.26×10−15, respectively [discovery set]; P = 4.13×10−10 and 5.15×10−11, respectively [validation set]). Among the 13 SNPs that showed genome-wide significance with total bilirubin levels, rs10929302 and rs6742078 showed the most significant association (P = 3.08×10−64 and 2.05×10−62, respectively [discovery set]; P = 1.33×10−116 and 2.24×10−118, respectively [validation set]). No genome-wide significant associations was found for ALT. Conclusions: We demonstrated that ABO, GGT1 and UGT1A family were associated with ALP, GGT and BIL, respectively in Korean population. These findings differ from reported results in GWAS in European populations in terms of associated genes and locations, suggesting different genetic mechanisms of liver enzyme regulation according to ethnicity. [ABSTRACT FROM AUTHOR]

Background & Aims: The association between nonalcoholic fatty liver disease and lung function has not been fully examined. The aim of this study was to clarify the association between nonalcoholic fatty liver disease and lung function in general population by performing cross‐sectional and longitudinal analysis. Methods: Participants without hepatic and respiratory disease who underwent regular health exams including hepatic sonography and spirometry with at least 3 years' follow‐up were included. In cross‐sectional analysis, the association between nonalcoholic fatty liver disease and lung function at baseline was examined with multiple regression models. The longitudinal analysis was performed by mixed linear regression models with propensity score matching. Results: Of 11 892 eligible participants (mean age, 47.7 years; male, 47.2%), 3815(32.1%) had nonalcoholic fatty liver disease based on sonography. In cross‐sectional analysis, the nonalcoholic fatty liver disease group had lower adjusted forced expiratory volume in 1‐second (men, 3.52 vs 3.44 L, P < .001; women, 2.62 vs 2.45 L, P < .001) and forced vital capacity (men, 4.33 vs 4.24 L, P < .001; women, 3.11 vs 2.97 L, P < .001) than the control group. In longitudinal analysis, during the mean follow‐up period of 6.6 years, there were no significant differences in forced expiratory volume in 1‐second or forced vital capacity decline rates between two groups in the propensity score‐matched cohorts (n = 4558). However, those with high nonalcoholic fatty liver disease fibrosis score and fibrosis‐4 (men, −21.7 vs −27.4 mL/y, P = .001; women, −22.4 vs −27.9 mL/y, P = .016) showed significantly faster decline in forced vital capacity compared to those with low scores. Conclusions: Nonalcoholic fatty liver disease was associated with decreased lung function at baseline but was not associated with accelerated lung function decline in the propensity score‐matched cohort. However, hepatic fibrosis was significantly associated with rapid forced vital capacity decline. [ABSTRACT FROM AUTHOR]

Background & Aims Physical activity ( PA) is inversely associated with nonalcoholic fatty liver disease ( NAFLD) prevalence. However, few studies evaluated the effect of PA on NAFLD incidence in regard to visceral adipose tissue ( VAT) and insulin resistance ( IR). We investigated whether PA at baseline and change in PA during follow-up have any effect on incident NAFLD. Methods We enrolled subjects who underwent health screenings between 2007 and 2008 and participated in voluntary follow-up between 2011 and 2013 (median 4.42 years). Incident NAFLD was defined as NAFLD absence at baseline and presence at follow-up by ultrasonography. PA was measured using a detailed questionnaire-based metabolic equivalent at baseline and follow-up; the difference during follow-up was calculated. Results Of the 1373 subjects enrolled, 288 (21.0%) developed NAFLD. Both total and leisure-time PA at baseline were inversely associated with incident NAFLD ( P for trend=.005 and .003 respectively). Decreased PA at follow-up was associated with increased incident NAFLD risk after adjusting for age, gender, body mass index, smoking, hypertension, diabetes and diet [hazard ratio ( HR) 1.45, 95% confidence interval ( CI) 1.04-2.02, 4th (most decreased PA) vs 1st quartile (increased PA), P=.028]. This relationship was attenuated but remained statistically significant after adjustment for VAT( HR 1.48, 95% CI 1.06-2.06, 4th vs 1st quartile) and IR( HR 1.59, 95% CI 1.11-2.27, 4th vs 1st quartile). Conclusions This study shows an independent protective effect of PA at baseline on incident NAFLD after 4-year follow-up. Furthermore, sustained or increased PA had a preventive effect on incident NAFLD independent of VAT and IR. [ABSTRACT FROM AUTHOR]

Background & Aims Limited evidence supports a role for physical activity ( PA) in nonalcoholic fatty liver disease ( NAFLD) independent of visceral obesity or/and insulin resistance. We investigated the association between PA and NAFLD while considering visceral adipose tissue ( VAT) and insulin resistance in a large general population. Methods Nonalcoholic fatty liver disease was diagnosed based on typical ultrasonographic findings. A detailed PA questionnaire included type, frequency, duration and length of time that the subject engaged in PA. PA was determined by a metabolic equivalent. VAT was evaluated by computed tomography taken at the umbilicus level. Results A total of 3718 subjects were enrolled in the analysis. After adjusting for age, gender, body mass index, smoking, hypertension, diabetes, soft drink and coffee consumption, the total PA was inversely associated with NAFLD [4th quartile (highest activities), odds ratio ( OR) 0.68, 95% confidence interval ( CI) 0.54-0.85; 3rd quartile, OR 0.74, 95% CI 0.59-0.93 vs. 1st quartile (lowest activities), P for trend <0.001]. After further adjusting for VAT or insulin resistance or both ( P for trend = 0.027, 0.001 and 0.040 respectively), this relationship was slightly attenuated but remained statistically significant. The leisure-time PA and weighted PA also had inverse associations with NAFLD independent of the VAT or insulin resistance or both. Conclusions This study showed an inverse association between various types of PA and the prevalence of NAFLD in a dose-dependent manner that was independent of visceral obesity and insulin resistance. This finding suggests a beneficial association between PA and NAFLD. [ABSTRACT FROM AUTHOR]

Simple Summary: We aimed to determine which of the various body compositions best reflects the risk of colorectal adenoma. Five body indices, including skeletal muscle index, fat mass index, muscle-to-fat ratio, visceral fat index, and skeletal muscle mass-to-visceral fat area ratio, measured by bioelectrical impedance analysis, reflected the risk of adenoma and high-risk adenoma. Among the various body indices, visceral fat index was the most important index associated with the risk of colorectal adenoma. We suggest that more attention should be paid to visceral fat when predicting the risk of colorectal adenoma. Objective: Although the incidence of colorectal adenomas increases with obesity, the role of various body compositions is still unknown. We aimed to determine which body composition best reflects the risk of colorectal adenomas. Methods: Patients aged 50–75 years who underwent colonoscopy and a bioelectrical impedance analysis (BIA) for a health check-up from 2017 to 2019 were retrospectively enrolled. The skeletal muscle index (SMI), fat mass index (FMI), and visceral fat index (VFI) were obtained using BIA. The muscle-to-fat ratio (MFR) and the skeletal muscle mass to visceral fat area ratio (SVR) were calculated. Results: Among 15,102 patients, 6605 (43.7%) had adenomas. SMI, FMI, MFR, VFI, and SVR were all associated with the risk of adenomas and high-risk adenomas in the age- and sex-adjusted model. When further adjusted for metabolic and lifestyle factors, VFI was the only factor significantly associated with the risk of colorectal adenomas and high-risk adenomas (adenomas: odds ratio (OR) 1.40, 95% confidence interval (CI) 1.22–1.61; high-risk adenomas: OR 1.47, 95% CI 1.16–1.87, for the highest quartile). Conclusion: Among the various body indices, VFI was the most important index associated with the development of colorectal adenoma. More attention should be paid to visceral fat when predicting the risk of colorectal adenomas. [ABSTRACT FROM AUTHOR]

Background and Aims: The utility of clinical information from esophagogastroduodenoscopy (EGD) reports has been limited because of its unstructured narrative format. We developed a natural language processing (NLP) pipeline that automatically extracts information about gastric diseases from unstructured EGD reports and demonstrated its applicability in clinical research. Methods: An NLP pipeline was developed using 2000 EGD and associated pathology reports that were retrieved from a single healthcare center. The pipeline extracted clinical information, including the presence, location, and size, for 10 gastric diseases from the EGD reports. It was validated with 1000 EGD reports by evaluating sensitivity, positive predictive value (PPV), accuracy, and F1 score. The pipeline was applied to 248,966 EGD reports from 2010–2019 to identify patient demographics and clinical information for 10 gastric diseases. Results: For gastritis information extraction, we achieved an overall sensitivity, PPV, accuracy, and F1 score of 0.966, 0.972, 0.996, and 0.967, respectively. Other gastric diseases, such as ulcers, and neoplastic diseases achieved an overall sensitivity, PPV, accuracy, and F1 score of 0.975, 0.982, 0.999, and 0.978, respectively. The study of EGD data of over 10 years revealed the demographics of patients with gastric diseases by sex and age. In addition, the study identified the extent and locations of gastritis and other gastric diseases, respectively. Conclusions: We demonstrated the feasibility of the NLP pipeline providing an automated extraction of gastric disease information from EGD reports. Incorporating the pipeline can facilitate large-scale clinical research to better understand gastric diseases. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome (MetS). However, the temporal relationship between NAFLD and MetS has yet to be evaluated, especially in young adults. In this study, we investigated whether NAFLD could be a precursor for MetS in metabolically healthy young adults. Using the Korean nationwide health screening database, we analyzed subjects aged 20–39 years who were free from any component of MetS between 2009 and 2012. A total of 1,659,192 subjects without excessive alcohol consumption or concomitant liver disease were categorized into three groups according to the fatty liver index (FLI): (1) NAFLD (FLI ≥ 60); (2) borderline NAFLD (30 ≤ FLI < 60); and (3) control (FLI < 30). During the 6,699,462 person-years of follow-up, 109,239 subjects developed MetS (16.3 per 1000-person-years). The NAFLD group and the borderline NAFLD group were associated with a higher risk of MetS than the control group (incidence rate ratios, 2.9 (95% confidence interval (CI), 2.7–3.1) for the NAFLD group and 2.1 (95% CI, 2.1–2.2) for the borderline NAFLD group, respectively). In addition, all of the metabolic components were positively associated with FLI in a proportional manner. NAFLD is associated with the future onset of MetS in young adults. Therefore, active lifestyle intervention is required for young adults diagnosed with NAFLD to prevent MetS and other metabolic diseases. [ABSTRACT FROM AUTHOR]

Computer-aided detection (CADe) systems have been actively researched for polyp detection in colonoscopy. To be an effective system, it is important to detect additional polyps that may be easily missed by endoscopists. Sessile serrated lesions (SSLs) are a precursor to colorectal cancer with a relatively higher miss rate, owing to their flat and subtle morphology. Colonoscopy CADe systems could help endoscopists; however, the current systems exhibit a very low performance for detecting SSLs. We propose a polyp detection system that reflects the morphological characteristics of SSLs to detect unrecognized or easily missed polyps. To develop a well-trained system with imbalanced polyp data, a generative adversarial network (GAN) was used to synthesize high-resolution whole endoscopic images, including SSL. Quantitative and qualitative evaluations on GAN-synthesized images ensure that synthetic images are realistic and include SSL endoscopic features. Moreover, traditional augmentation methods were used to compare the efficacy of the GAN augmentation method. The CADe system augmented with GAN synthesized images showed a 17.5% improvement in sensitivity on SSLs. Consequently, we verified the potential of the GAN to synthesize high-resolution images with endoscopic features and the proposed system was found to be effective in detecting easily missed polyps during a colonoscopy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: In Korea, where gastric cancer is highly prevalent, biennial endoscopy is recommended among individuals over 40. Even under regular screening, some are still diagnosed at advanced stages. We aimed to identify characteristics of interval gastric neoplasms (IGNs) with rapid progression.Results: Newly-diagnosed gastric neoplasms detected in screening endoscopy between January 2004 and May 2016 were reviewed. Among them, those who had previous endoscopy within 2 years were enrolled. Endoscopic findings, family history of gastric cancer, smoking, and H. pylori status were analysed. Totally, 297 IGN cases were enrolled. Among them, 246 were endoscopically treatable IGN (ET-IGN) and 51 were endoscopically untreatable IGNs (EUT-IGN) by the expanded criteria for endoscopic submucosal dissection. Among EUT-IGNs, 78% were undifferentiated cancers (40/51) and 33% showed submucosal invasion (13/40). They were median 2.0 cm in size and more commonly located in the proximal stomach than ET-IGNs (70.6% vs. 41.9%, p < 0.001). EUT-IGN was independently related with age < 60 (OR, 2.09; 95%CI, 1.03-4.26, p = 0.042), H. pylori (OR, 2.81; 95%CI, 1.20-6.63, p = 0.018), and absent/mild gastric atrophy (OR, 2.67; 95%CI, 1.25-5.72, p = 0.011). Overall and disease-specific survival were not significantly different between the two groups, however EUT-IGN tended to have short disease-specific survival (overall survival, p = 0.143; disease-specific survival, p = 0.083).Conclusions: Uniform screening endoscopy with two-year interval seems not enough for rapid-growing gastric neoplasms, such as undifferentiated cancers. They tended to develop in adults younger than 60 with H. pylori infection without severe gastric atrophy. More meticulous screening, especially for proximal lesions is warranted for adults younger than 60 with H. pylori infection before development of gastric atrophy. [ABSTRACT FROM AUTHOR]

Background and Aim: In East Asia, colonic diverticulosis develops most commonly in the right colon and is known to have different characteristics compared with left‐sided one. This study was designed to investigate whether right‐colonic diverticulosis is associated with posteriori dietary patterns. Methods: We retrospectively reviewed medical records of prospectively collected cohort that received health check‐up in Korea between May 2011 and January 2012. Their anthropometric data, biochemical results, medication history, underlying diseases, colonoscopic findings, and dietary data obtained from semi‐quantitative food‐frequency questionnaire were analyzed. Three dietary patterns were identified using factor analysis: healthy dietary pattern (vegetables, fish, seaweed, fruits, and beans), meat dietary pattern (red meat, processed meat/fish, fried noodle, poultry, and cephalopods), and snack dietary pattern (bread, sweets, dairy products, nuts, and rice cake). Results: Out of the total 1911 patients, 203 (10.6%) had right‐colonic diverticulosis, 21 (1.1%) had pan‐colonic diverticulosis, and 12 (0.6%) had left‐colonic diverticulosis. Among the total, none of the three patterns were associated with right‐colonic diverticulosis, under adjustment with age, gender, body mass index, metabolic syndrome, and total energy intake. However, among women, meat dietary pattern was positively associated with right‐colonic diverticulosis (odds ratio 1.866, 95% confidence interval: 1.0983–3.173, P = 0.021). Conclusion: This study demonstrated that meat dietary pattern is positively associated with right‐colonic diverticulosis among women. [ABSTRACT FROM AUTHOR]

Background: To prevent colorectal cancer, high-quality colonoscopy is advocated, undertaken by endoscopists with high adenoma detection rates (ADRs). Despite reports that various factors may impact ADRs, the significance of such factors is still unclear.Aims: The analysis was aimed at quality-oriented interventions for boosting ADRs.Methods: Study enrollees were adults subjected to screening colonoscopy between September 2013 and August 2016 at the Gangnam Center of Seoul National University Hospital Healthcare System. The investigation entailed six periods (P1-6) of 6 months each, during which serial multidirectional quality improvement efforts were instituted. In particular, we sought to further educate endoscopists, provide feedback on individual ADRs, and introduce a split-dose regimen, gauging results via the Boston Bowel Preparation Score. Changes in polyp detection rates (PDRs) and ADRs were then analyzed.Results: A total of 13,430 colonoscopies were undertaken by 15 experienced endoscopists. Overall, the ADR increased from 45.6% (P1) to 48.2% (P6, p < 0.001). The PDR, ADR, and advanced adenoma detection rate (AdvADR) showed the greatest increases between P3 and P4 [PDR 67.8% → 71.2% (p < 0.001); ADR 44.1% → 47.7% (p = 0.001); AdvADR 2.3% → 3.3% (p = 0.028)] in keeping with the introduction of a split-dose regimen. The sessile serrated adenoma detection rate (SSADR) increased substantially from 2.1% (P1) to 7.9% (P6, p < 0.001), with the largest gain between P1 and P2, just after education (p = 0.023).Conclusions: Successful quality improvement in colonoscopy was achieved through comprehensive multidirectional efforts in education, feedback, and enhanced bowel preparation. Achieving high-level bowel preparation was paramount in ADR improvement. The SSADR was improved through education. [ABSTRACT FROM AUTHOR]

Previous epidemiological studies focusing on the association between liver disease and atrial fibrillation (AF) show interesting but inconsistent findings. Patients with liver disease have a higher AF risk; however, it is unknown whether the liver fibrosis index can predict AF risk. The medical records of a healthy population undergoing routine health examinations at Healthcare System Gangnam Center, Seoul National University Hospital, were reviewed retrospectively. After excluding subjects with a history of liver disease and known cardiovascular disease, 74,946 subjects with nonalcoholic fatty liver disease (NAFLD) were evaluated. The mean age was 51 ± 11 years, and 71.9% were male. AF was found in 380 (0.5%) subjects. Using univariate analyses, age, male sex, body mass index, hypertension, and diabetes were significantly associated with AF. The fibrosis 4 index (FIB 4) showed significant correlations with AF [unadjusted odds ratio (OR) 3.062 and 95% confidence interval (CI) 2.605–3.600, p = 0.000; adjusted OR 2.255 and 95% CI 1.744–2.915, p = 0.000, with cardiometabolic risk factors adjusted]. In conclusion, NAFLD subjects with higher FIB 4 were associated with increased AF risk. The noninvasive determination of liver fibrosis indices can have clinical implications on the early identification of NAFLD in patients at risk for AF. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Genome-wide association study of metabolic dysfunction-associated fatty liver disease in a Korean population" published in Scientific Reports. The correction addresses errors in the affiliations of the authors. The correct affiliations for Seung-Won Oh are listed, and the correct affiliation for affiliation 4 is provided. The original article has been corrected. [Extracted from the article]

Background: Chronic systemic inflammation is an important causative factor in the pathogenesis of atherosclerosis. However, the effect of chronic Helicobacter pylori (Hp) infection on arterial stiffness, a predictor of cardiovascular events, remains unclear. We evaluated the association between Hp infection and arterial stiffness in asymptomatic healthy individuals. Methods: Arterial stiffness was evaluated using the cardio-ankle vascular index (CAVI). We included subjects who underwent CAVI and anti-Hp IgG antibody evaluations, simultaneously, between March 2013 and July 2017. Demographic characteristics and metabolic and cardiovascular parameters were compared with respect to anti-Hp IgG antibody status. Multivariable logistic regression analyses were performed to determine the effect of Hp-seropositivity and conventional cardiovascular risk factors on arterial stiffness. Results: Of 2,251 subjects, 1,326 (58.9%) were included in the Hp-seropositive group. Median age (P < 0.001) and systolic blood pressure (P = 0.027) were significantly higher in the Hp-seropositive than in the Hp-seronegative group. Levels of LDL-cholesterol were significantly higher in the Hp-seropositive than in the Hp-seronegative group (P = 0.016). Other serum metabolic parameters were not significantly different between the two groups. The median CAVI value and the proportion of subjects with a CAVI ≥ 8 were significantly higher in the Hp-seropositive than in the Hp-seronegative group (both P < 0.001). On multivariable logistic regression analyses, Hp-seropositivity, age, body mass index, waist circumference, smoking, hypertension, diabetes mellitus, and dyslipidemia were significantly associated with high CAVI values. In the subgroup analysis conducted according to age group, a tendency towards an increased association between Hp-seropositivity and CAVI was observed with increasing age, even though the difference did not reach the statistical significance. Conclusions: Hp-seropositivity was significantly associated with arterial stiffness. Hp infection may contribute to the development of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) plays a significant role in coronary atherosclerosis, independent of shared metabolic risk factors. The measurement of the controlled attenuation parameter (CAP) has shown to allow early and noninvasive detection of NAFLD at subclinical stage. We evaluated the significance of CAP-defined NAFLD in association with the presence of any type of coronary plaques and different plaque compositions.Methods: We conducted a retrospective cohort of apparently healthy subjects who had liver Fibroscan and coronary computed tomography during health screening exams.Results: A greater number of subjects with CAP-defined NAFLD was found in group with coronary plaques (61.3% vs. 73.5%, p = 0.005 without vs. with any type of plaque). From multivariate regression model, CAP ≥ 222 dB/m was an independent and significant parameter associated with the presence of coronary plaques, after adjusting possible confounders (OR 1.624, 95% 1.047-2.518, p = 0.030). Interestingly, CAP ≥ 222 dB/m was significantly associated with non-calcified plaque (adjusted OR 3.528, 95% CI 1.463-8.511, p = 0.005), whereas it was not significant in calcified plaques (p = 0.171).Conclusion: CAP-defined NAFLD is independently associated with coronary plaques, especially non-calcified plaques. The association between NAFLD and non-calcified plaques suggests that particular attention should be given to the subjects with NAFLD for primary prevention. [ABSTRACT FROM AUTHOR]

Background & aims: The impact of marijuana on nonalcoholic fatty liver disease (NAFLD) is largely unknown. We studied the association between marijuana and NAFLD utilizing cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) from 2005–2014 and NHANES III (1988–1994). Methods: Suspected NAFLD was diagnosed if serum alanine aminotransferase (ALT) was > 30 IU/L for men and > 19 IU/L for women in the absence of other liver diseases (NHANES 2005–2014). In NHANES III cohort, NAFLD was defined based on ultrasonography. Results: Of the 14,080 (NHANES 2005–2014) and 8,286 (NHANES III) participants, prevalence of suspected NAFLD and ultrasonographically-diagnosed NAFLD were inversely associated with marijuana use (p < 0.001). Compared to marijuana-naïve participants, marijuana users were less likely to have suspected NAFLD (odds ratio [OR]: 0.90, 95% confidence interval [CI]: 0.82–0.99 for past user; OR: 0.68, 95% CI: 0.58–0.80 for current user) and ultrasonographically-diagnosed NAFLD (OR: 0.75, 95% CI: 0.57–0.98 for current user) in the age, gender, ethnicity-adjusted model. On multivariate analysis, the ORs for suspected NAFLD comparing current light or heavy users to non-users were 0.76 (95% CI 0.58–0.98) and 0.70 (95% CI 0.56–0.89), respectively (P for trend = 0.001) with similar trends in ultrasonographically-diagnosed NAFLD (OR: 0.77, 95% CI: 0.59–1.00 for current user; OR: 0.71, 95% CI: 0.51–0.97 for current light user). In insulin resistance-adjusted model, marijuana use remained an independent predictor of lower risk of suspected NAFLD. Conclusions: In this nationally representative sample, active marijuana use provided a protective effect against NAFLD independent of known metabolic risk factors. The pathophysiology is unclear and warrants further investigation. [ABSTRACT FROM AUTHOR]

Abstract: Background: Inverse correlations of high serum bilirubin with metabolic and cardiovascular disease have been suggested. However, anti-atherogenic effects of bilirubin have not been well-established in terms of the presence of plaques and stenosis identified in coronary computed tomography (CT). Methods: A cross-sectional study was conducted on 2862 men who were free of cardiovascular disease and underwent coronary CT as part of a routine medical screening examination. Coronary stenotic lesions were considered to be incidences of coronary atherosclerosis, and stenosis was classified as stenosis <50% or ≥50%, according to degree of stenosis. Results: The prevalences of coronary atherosclerosis and stenosis ≥50% in subjects with elevated bilirubin levels (>1.2 mg/dL) were lower than those in subjects with normal bilirubin levels (≤1.2 mg/dL) (19.9% vs. 27.9%, p < 0.001, 8.5% vs. 10.3%, p = 0.044). Bilirubin was inversely associated with total plaques (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.48–0.73 in the 4th quartile vs. 1st quartile) and calcified plaques (OR 0.60, 95% CI 0.49–0.75) in univariate analysis. After adjusting for traditional risk factors, it was found that coronary atherosclerosis (OR 0.73, 95% CI 0.56–0.94 in the 4th quartile vs. 1st quartile) and calcified plaque (OR 0.66, 95% CI 0.53–0.84) were inversely associated with the bilirubin grade in a dose-dependent manner. Conclusions: The serum bilirubin level was inversely associated with coronary atherosclerosis and calcified plaques in a dose-dependent manner. These results suggested that serum bilirubin could be used as a protective biomarker of coronary artery disease. [Copyright &y& Elsevier]