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.

Gamma-glutamyl transferase and the risk of all-cause and disease-specific mortality in patients with diabetes: A nationwide cohort study.

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.

Density clustering-based automatic anatomical section recognition in colonoscopy video using deep learning.

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.

Genetic and Metabolic Characteristics of Lean Nonalcoholic Fatty Liver Disease in a Korean Health Examinee Cohort.

Background/Aims: The pathophysiology of lean nonalcoholic fatty liver disease (NAFLD) is unclear but has been shown to be associated with more diverse pathogenic mechanisms than that of obese NAFLD. We investigated the characteristics of genetic or metabolic lean NAFLD in a health checkup cohort. Methods: This retrospective cross-sectional study analyzed single nucleotide polymorphism data for 6,939 health examinees. Lean individuals were categorized according to a body mass index cutoff of 23 kg/m2. Single nucleotide polymorphisms were analyzed using genotyping arrays. Results: The prevalence of lean NAFLD was 21.6% among all participants with NAFLD, and the proportion of lean NAFLD was 18.5% among lean participants. The prevalence of metabolic syndrome and diabetes among lean patients with NAFLD was 12.4% and 10.4%, respectively. Lean NAFLD appeared to be metabolic-associated in approximately 20.1% of patients. The homozygous minor allele (GG) of PNPLA3 (rs738409) and heterozygous minor alleles (CT, TT) of TM6SF2 (rs58542926) were associated with lean NAFLD. However, the prevalence of fatty liver was not associated with the genetic variants MBOAT7 (rs641738), HSD17B13 (rs72613567), MARC1 (rs2642438), or AGXT2 (rs2291702) in lean individuals. Lean NAFLD appeared to be associated with PNPLA3 or TM6SF2 genetic variation in approximately 32.1% of cases. Multivariate risk factor analysis showed that metabolic risk factors, genetic risk variants, and waist circumference were independent risk factors for lean NAFLD. Conclusions: In a considerable number of patients, lean NAFLD did not appear to be associated with known genetic or metabolic risk factors. Further studies are required to investigate additional risk factors and gain a more comprehensive understanding of lean NAFLD.

Predicted pro-inflammatory hs-CRP score and non-alcoholic fatty liver disease.

Background: Non-alcoholic fatty liver disease (NAFLD) is a major contributor to liver diseases globally, yet there are limited studies investigating the impact of diet and lifestyle factors on its development. This study aimed to examine the association between the prevalence of NAFLD and predicted pro-inflammatory high-sensitivity C-reactive protein (hs-CRP) score. Methods: We included 1,076 Korean adults who underwent a medical examination at the Seoul National University Hospital Gangnam Healthcare Center in Korea between May and December 2011 and updated in 2021. The predicted pro-inflammatory hs-CRP score was derived from pro-inflammatory demographic, lifestyle, dietary, and anthropometric factors, and NAFLD was diagnosed using liver ultrasound. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of NAFLD odds according to predicted pro-inflammatory hs-CRP score were estimated using logistic regression at a two-sided P < 0.05. Results: Among the 1,076 participants, 320 had NAFLD. The multivariable-adjusted ORs and 95% CIs for NAFLD by tertiles of predicted pro-inflammatory hs-CRP score were 1.00, 3.30 (2.06, 5.30), 18.25 (10.47, 31.81; P < 0.0001) in men and women combined, 1.00, 1.77 (1.10, 2.84), and 3.26 (2.02, 5.28; P < 0.0001) among men only, and 1.00, 3.03 (1.39, 6.62), and 16.71 (7.05, 39.63; P < 0.0001) among women only. Conclusions: Predicted pro-inflammatory hs-CRP score was associated with higher odds of NAFLD. Adopting dietary and lifestyle changes related to lower inflammation might be a valuable strategy for preventing NAFLD.

Association of changes in obesity and abdominal obesity status with early-onset colorectal cancer risk: a nationwide population-based cohort study.

Background and aims: The incidence of early-onset colorectal cancer (EO-CRC, diagnosed before 50 years of age) has increased in recent decades. The aim of this study was to investigate the association between changes in obesity status and EO-CRC risk. Methods: From a nationwide population-based cohort, individuals <50 years old who participated in the national health checkup program in both 2009 and 2011 were included. Obesity was defined as a body mass index ≥25 kg/m2. Abdominal obesity was defined as a waist circumference ≥ 90 cm in men and ≥ 85 cm in women. Participants were classified into 4 groups according to the change in obesity (normal/normal, normal/obese, obese/normal, persistent obese) and abdominal obesity (normal/normal, normal/abdominal obesity, abdominal obesity/normal, persistent abdominal obesity) status. Participants were followed up until 2019 and censored when they became 50 years old. Results: Among 3,340,635 participants, 7,492 patients were diagnosed with EO-CRC during 7.1 years of follow-up. The risk of EO-CRC was higher in the persistent obesity and persistent abdominal obesity groups than in the normal/normal groups (hazard ratio (HR) [95% confidence interval (CI)] = 1.09 [1.03-1.16] and 1.18 [1.09-1.29], respectively). Participants with both persistent obesity and abdominal obesity had a higher EO-CRC risk than those in the normal/normal groups for both [HR (95% CI) = 1.19 (1.09-1.30)]. Conclusion: Persistent obesity and persistent abdominal obesity before the age of 50 are associated with a slightly increased risk of EO-CRC. Addressing obesity and abdominal obesity in young individuals might be beneficial in reducing the risk of EO-CRC.

Association between the fatty liver index and the risk of fracture among individuals over the age of 50 years: a nationwide population-based study.

Background and purpose: The association between fatty liver and fracture risk has not been firmly established. In this study, we investigated the relationship between the fatty liver index (FLI) and the incidence of fractures among individuals ≥50 years of age, using a nationwide population-based cohort. Methods: Data from the Korean National Health Insurance System between January 2009 and December 2019 were analyzed using the Cox proportional hazards model. Fatty liver status was defined using FLI. Newly diagnosed fractures were identified based on insurance claim data. Results: Among the 3,384,457 individuals who met our inclusion criteria over the study period, 444,203 cases of incident fractures were identified over a median follow-up of 10.3 years. On multivariate analysis, the risk of fracture was significantly higher among individuals with a higher FLI score compared to those with an FLI<30, with adjusted hazard ratio [aHR] and 95% confidence interval [CI] as follows: FLI 30-59 group, aHR 1.04 and 95% CI 1.03-1.05; and FLI ≥60 group, aHR 1.12 and 95% CI 1.10-1.13. A higher FLI was associated with a greater risk of hip (aHR 1.23 and 1.52 for the FLI 30-59 and FLI ≥60 group, respectively) and vertebral fracture (aHR 1.08 and 1.16 for the FLI 30-59 and FLI≥60 group, respectively). The association between the risk for fracture and FLI ≥60 was prominent for non-obese than obese individuals (aHR 1.25 and 95% CI, 1.22-1.27 versus 1.06 and 1.05-1.08, respectively). Conclusions: A high FLI is associated with an increased risk of hip and vertebral fractures among individuals ≥50 years of age, suggestive of an association between a higher FLI and osteoporotic fractures.

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.

The association between alcohol consumption and the risk of hepatocellular carcinoma according to glycemic status in Korea: A nationwide population-based study.

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.

Differential risk of 23 site-specific incident cancers and cancer-related mortality among patients with metabolic dysfunction-associated fatty liver disease: a population-based cohort study with 9.7 million Korean subjects.

INTRODUCTION: Although an association between metabolic dysfunction-associated fatty liver disease (MAFLD) and cardiovascular disease or overall mortality has been reported, it is unclear whether there is an association between MAFLD and cancer incidence or mortality. We aimed to investigate the differential risk of all- and site-specific cancer incidence and mortality according to MAFLD subgroups categorized by additional etiologies of liver disease. METHODS: Using the Korean National Health Insurance Service database, we stratified the participants into three groups: (1) single-etiology MAFLD (S-MAFLD) or MAFLD of pure metabolic origin; (2) mixed-etiology MAFLD (M-MAFLD) or MAFLD with additional etiological factor(s) (i.e., concomitant liver diseases and/or heavy alcohol consumption); and (3) non-MAFLD. Hepatic steatosis and fibrosis were defined using the fatty liver index and the BARD score, respectively. Cox proportional hazards regression was performed to estimate the risk of cancer events. RESULTS: Among the 9,718,182 participants, the prevalence of S-MAFLD and M-MAFLD was 29.2% and 6.7%, respectively. During the median 8.3 years of follow-up, 510,330 (5.3%) individuals were newly diagnosed with cancer, and 122,774 (1.3%) cancer-related deaths occurred among the entire cohort. Compared with the non-MAFLD group, the risk of all-cancer incidence and mortality was slightly higher among patients in the S-MAFLD group (incidence, adjusted hazard ratio [aHR] = 1.03; 95% confidence interval [CI]: 1.02-1.04; mortality, aHR = 1.06; 95% CI: 1.04-1.08) and highest among patients with M-MAFLD group (incidence, aHR = 1.31; 95% CI: 1.29-1.32; mortality, aHR = 1.45; 95% CI: 1.42-1.48, respectively). The M-MAFLD with fibrosis group (BARD score ≥ 2) showed the highest relative risk of all-cancer incidence (aHR = 1.38, 95% CI = 1.36-1.39), followed by the M-MAFLD without fibrosis group (aHR = 1.09, 95% CI = 1.06-1.11). Similar trends were observed for cancer-related mortality. CONCLUSIONS: MAFLD classification, by applying additional etiologies other than pure metabolic origin, can be used to identify a subgroup of patients with poor cancer-related outcomes.

Impact of 3-second rule for high confidence assignment on the performance of endoscopists for the real-time optical diagnosis of colorectal polyps.

BACKGROUND: Confusion between high and low confidence decisions in optical diagnosis hinders the implementation of real-time optical diagnosis in clinical practice. We evaluated the effect of a 3-second rule (decision time limited to 3 seconds for a high confidence assignment) in expert and nonexpert endoscopists. METHODS: This single-center prospective study included eight board-certified gastroenterologists. A 2-month baseline phase used standard real-time optical diagnosis for colorectal polyps < 10 mm and was followed by a 6-month intervention phase using optical diagnosis with the 3-second rule. Performance, including high confidence accuracy, and Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) and Simple Optical Diagnosis Accuracy (SODA) thresholds, was measured. RESULTS: Real-time optical diagnosis was performed on 1793 patients with 3694 polyps. There was significant improvement in high confidence accuracy between baseline and intervention phases in the nonexpert group (79.2 % vs. 86.3 %; P = 0.01) but not in the expert group (85.3 % vs. 87.5 %; P = 0.53). Using the 3-second rule improved the overall performance of PIVI and SODA in both groups. CONCLUSIONS: The 3-second rule was effective in improving real-time optical diagnosis performance, especially in nonexperts.

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.

Effects of additive interactions among obesity, visceral adiposity, and sarcopenia on nonalcoholic fatty liver disease.

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.

Lean or diabetic subtypes predict increased all-cause and disease-specific mortality in metabolic-associated fatty liver disease.

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.

Gamma-glutamyl transferase and risk of all-cause and disease-specific mortality: a nationwide cohort study.

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.

Impact of Evolutionary Changes in Nonalcoholic Fatty Liver Disease on Lung Function Decline.

Background/Aims: A relationship between fatty liver and lung function impairment has been identified, and both are independently associated with metabolic dysfunction. However, the temporal relationship between changes in fatty liver status and lung function and their genome-wide association remain unclear. Methods: This longitudinal cohort consisted of subjects who received serial health check-ups, including liver ultrasonography and spirometry, for ≥3 years between 2003 and 2015. Lung function decline rates were classified as "slow" and "accelerated" and compared among four different sonographic changes in steatosis status: "normal," "improved," "worsened," and "persistent." A genome-wide association study was conducted between the two groups: normal/improved steatosis with a slow decline in lung function versus worsened/persistent steatosis with an accelerated decline in lung function. Results: Among 6,149 individuals, the annual rates of decline in forced vital capacity (FVC) and forced expiratory volume measured in the first second of exhalation (FEV1) were higher in the worsened/persistent steatosis group than in the normal/improved steatosis group. In multivariable analysis, persistent or worsened status of fatty liver was significantly associated with accelerated declines in FVC (persistent status, odds ratio [OR]=1.22, 95% confidence interval [CI]=1.04-1.44; worsened status, OR=1.30, 95% CI=1.12-1.50), while improved status of fatty liver was significantly associated with slow declines in FEV1 (OR=0.77, 95% CI=0.64-0.92). The PNPLA3 risk gene was most strongly associated with steatosis status change and accelerated declines in FVC (rs12483959, p=2.61×10-7) and FEV1 (rs2294433, p=3.69×10-8). Conclusions: Regression of fatty liver is related to lung function decline. Continuing efforts to improve fatty liver may preserve lung function, especially for subjects with a high genetic risk.

The association of fatty liver index and BARD score with all-cause and cause-specific mortality in patients with type 2 diabetes mellitus: a nationwide population-based study.

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.

Visceral Obesity Is a More Important Factor for Colorectal Adenomas than Skeletal Muscle or Body Fat.

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.

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.