1.Evolutionary changes in metabolic dysfunction-associated steatotic liver disease and risk of hepatocellular carcinoma: A nationwide cohort study
Seogsong JEONG ; Yun Hwan OH ; Joseph C AHN ; Seulggie CHOI ; Sun Jae PARK ; Hye Jun KIM ; Gyeongsil LEE ; Joung Sik SON ; Heejoon JANG ; Dong Hyeon LEE ; Meng SHA ; Lei CHEN ; Won KIM ; Sang Min PARK
Clinical and Molecular Hepatology 2024;30(3):487-499
Background/Aims:
To determine the association between evolutionary changes in metabolic dysfunction-associated steatotic liver disease (MASLD) status and the risk of hepatocellular carcinoma (HCC) in a nationwide population-based cohort.
Methods:
Information on study participants was derived from the Korea National Health Insurance Service database. The study population consisted of 5,080,410 participants who underwent two consecutive biennial health screenings between 2009 and 2012. All participants were followed up until HCC, death, or 31 December 2020. The association of evolutionary changes in MASLD status, as assessed by the fatty liver index and cardiometabolic risk factors, including persistent non-MASLD, resolved MASLD, incident MASLD, and persistent MASLD, with HCC risk was evaluated using multivariable-adjusted Cox proportional hazards regression.
Results:
Among the 5,080,410 participants with 39,910,331 person-years of follow-up, 4,801 participants developed HCC. The incidence of HCC in participants with resolved, incident, and persistent MASLD was approximately 2.2-, 2.3-, and 4.7-fold higher, respectively, than that in those with persistent non-MASLD among the Korean adult population. When stratifying the participants according to the evolutionary change in MASLD status, persistent (adjusted hazard ratio [aHR], 2.94; 95% confidence interval [CI], 2.68–3.21; P<0.001), incident (aHR, 1.85; 95% CI, 1.63–2.10; P<0.001), and resolved MASLD (aHR, 1.33; 95% CI, 1.18–1.50; P<0.001) had an increased risk of HCC compared to persistent non-MASLD.
Conclusions
The evolutionary changes in MASLD were associated with the differential risk of HCC independent of metabolic risk factors and concomitant medications, providing additional information on the risk of HCC stratification in patients with MASLD.
3.Association of Change in Smoking Status and Subsequent Weight Change with Risk of Nonalcoholic Fatty Liver Disease
Seogsong JEONG ; Yun Hwan OH ; Seulggie CHOI ; Jooyoung CHANG ; Sung Min KIM ; Sun Jae PARK ; Yoosun CHO ; Joung Sik SON ; Gyeongsil LEE ; Sang Min PARK
Gut and Liver 2023;17(1):150-158
Background/Aims:
Smoking is considered a risk factor for the development of nonalcoholic fatty liver disease (NAFLD). However, the association of a weight change after a change in smoking status and the risk of NAFLD remains undetermined.
Methods:
This study used the Korean National Health Insurance Service-National Sample Cohort. Based on the first (2009 to 2010) and second (2011 to 2012) health examination periods, 139,180 adults aged at least 40 years were divided into nonsmoking, smoking cessation, smoking relapse, and sustained smoking groups. NAFLD was operationally defined using the fatty liver index. The adjusted odds ratio (aOR) and 95% confidence interval (CI) were calculated using multivariable-adjusted logistic regression.
Results:
Compared to nonsmoking with no body mass index (BMI) change, the risk of NAFLD was significantly increased among subjects with BMI gain and nonsmoking (aOR, 4.07; 95% CI, 3.77 to 4.39), smoking cessation (aOR, 5.52; 95% CI, 4.12 to 7.40), smoking relapse (aOR, 7.51; 95% CI, 4.81 to 11.72), and sustained smoking (aOR, 6.65; 95% CI, 5.33 to 8.29), whereas the risk of NAFLD was reduced among participants with BMI loss in all smoking status groups. In addition, smoking cessation (aOR, 1.76; 95% CI, 1.35 to 2.29) and sustained smoking (aOR, 1.64; 95% CI, 1.39 to 1.94) were associated with higher risk of NAFLD among participants with no BMI change.The liver enzyme levels were higher among participants with smoking cessation and BMI gain.
Conclusions
Monitoring and management of weight change after a change in smoking status may be a promising approach to reducing NAFLD.
4.Association of non-alcoholic fatty liver disease with incident dementia later in life among elder adults
Seogsong JEONG ; Yun Hwan OH ; Seulggie CHOI ; Jooyoung CHANG ; Sung Min KIM ; Joung Sik SON ; Gyeongsil LEE ; Joseph C AHN ; Dong Hyeon LEE ; Bo Kyung KOO ; Won KIM ; Sang Min PARK
Clinical and Molecular Hepatology 2022;28(3):510-521
Background/Aims:
Accumulating evidence suggests a link between non-alcoholic fatty liver disease (NAFLD) and brain health. However, population-based evidence on the association between NAFLD and dementia remains unclear. This study was conducted to determine the association between NAFLD and incident dementia.
Methods:
The study population included 608,994 adults aged ≥60 years who underwent health examinations between 2009 and 2010. Data were collected from the Korean National Health Insurance Service database. NAFLD was assessed using the fatty liver index (FLI). A Cox proportional hazards regression model was used to determine the association between NAFLD and dementia.
Results:
During the 6,495,352 person-years of follow-up, 48,538 participants (8.0%) developed incident dementia. The participants were classified into low (FLI <30), intermediate (FLI ≥30 and <60), and high (FLI ≥60) groups. In the overall study population, the FLI groups were associated with a risk of dementia (P for trend <0.001). After propensity score matching, a low FLI was associated with a reduced risk of dementia (adjusted hazard ration [aHR], 0.96; 95% confidence interval [CI], 0.93–0.98; P=0.002), whereas a high FLI (NAFLD) was associated with an increased risk of dementia (aHR, 1.05; 95% CI, 1.02–1.08; P=0.001). A higher risk of dementia in the high FLI group than in the intermediate FLI group was attributed to Alzheimer’s disease (aHR, 1.04; 95% CI, 1.01–1.07; P=0.004) rather than vascular dementia (aHR, 0.94; 95% CI, 0.75–1.18; P=0.602).
Conclusions
NAFLD was associated with an increased risk of dementia, which was attributed to an increased risk of Alzheimer’s disease.
5.Metabolic Dysfunction-Associated Fatty Liver Disease Better Predicts Incident Cardiovascular Disease
Seogsong JEONG ; Yun Hwan OH ; Seulggie CHOI ; Jooyoung CHANG ; Sung Min KIM ; Joung Sik SON ; Gyeongsil LEE ; Won KIM ; Sang Min PARK
Gut and Liver 2022;16(4):589-598
Background/Aims:
Metabolic dysfunction (MD)-associated fatty liver disease is a new positive diagnostic criterion based on hepatic steatosis and MD. However, a comprehensive evaluation on the association of MD and hepatic steatosis with incident cardiovascular disease (CVD) has yet to be performed.
Methods:
This retrospective cohort study included 333,389 participants from the Korean National Health Insurance Service database who received a health examination between 2009 and 2010. Hepatic steatosis was defined using the Korean National Health and Nutrition Examination Survey-derived nonalcoholic fatty liver disease scoring system. Cox proportional hazards regression was adopted to determine the adjusted hazard ratio (aHR) with 95% confidence interval (CI) for CVD according to the presence of hepatic steatosis and MD, as well as the composite term.
Results:
This study included 179,437 men and 153,952 women with a median age of 57 years.Hepatic steatosis with MD (aHR, 2.00; 95% CI, 1.89 to 2.13) and without MD (aHR, 1.30; 95% CI, 1.10 to 1.54) significantly increased the risk of CVD compared to no steatosis without MD (reference). However, steatosis revealed no significant difference in the risk of CVD compared to no steatosis among participants with one MD (aHR, 1.09; 95% CI, 0.91 to 1.30). In participants with steatosis, the presence of one and ≥2 MDs had aHR values of 1.25 (95% CI, 0.87 to 1.79) and 1.71 (95% CI, 1.22 to 2.41), respectively, compared to no MD.
Conclusions
Combined consideration of hepatic steatosis and MD was significantly associated with increased CVD risk and showed better predictive performance for CVD than hepatic steatosis or MD alone.
6.Development and validation of prediction equations for the assessment of muscle or fat mass using anthropometric measurements, serum creatinine level, and lifestyle factors among Korean adults
Gyeongsil LEE ; Jooyoung CHANG ; Seung-sik HWANG ; Joung Sik SON ; Sang Min PARK
Nutrition Research and Practice 2021;15(1):95-105
BACKGROUND/OBJECTIVES:
The measurement of body composition, including muscle and fat mass, remains challenging in large epidemiological studies due to time constraint and cost when using accurate modalities. Therefore, this study aimed to develop and validate prediction equations according to sex to measure lean body mass (LBM), appendicular skeletal muscle mass (ASM), and body fat mass (BFM) using anthropometric measurement, serum creatinine level, and lifestyle factors as independent variables and dual-energy X-ray absorptiometry as the reference method.
SUBJECTS/METHODS:
A sample of the Korean general adult population (men:7,599; women:10,009) from the Korean National Health and Nutrition Examination Survey 2008–2011 was included in this study. The participants were divided into the derivation and validation groups via a random number generator (with a ratio of 70:30). The prediction equations were developed using a series of multivariable linear regressions and validated using the Bland– Altman plot and intraclass correlation coefficient (ICC).
RESULTS:
The initial and practical equations that included age, height, weight, and waist circumference had a different predictive ability for LBM (men: R2 = 0.85, standard error of estimate [SEE] = 2.7 kg; women: R2 = 0.78, SEE = 2.2 kg), ASM (men: R2= 0.81, SEE = 1.6 kg; women: R2 = 0.71, SEE = 1.2 kg), and BFM (men: R2 = 0.74, SEE = 2.7 kg; women: R2 = 0.83, SEE = 2.2 kg) according to sex. Compared with the first prediction equation, the addition of other factors, including serum creatinine level, physical activity, smoking status, and alcohol use, resulted in an R2 that is higher by 0.01 and SEE that is lower by 0.1.
CONCLUSIONS
All equations had low bias, moderate agreement based on the Bland–Altman plot, and high ICC, and this result showed that these equations can be further applied to other epidemiologic studies.
7.Association between Consumption of Sugar-Sweetened Beverages and Risk of Cardiovascular Disease in Korean Men: Analysis Based on the Korea National Health and Nutrition Examination Survey 2014–2016
Su-Ok KIM ; Eun Mi BAE ; Ye-Na LEE ; Joung Sik SON
Korean Journal of Family Medicine 2021;42(3):212-218
Background:
This study aimed to evaluate the association between the high risk of cardiovascular disease (CVD) and the consumption of sugar-sweetened beverages (SSBs) in Korean men.
Methods:
This cross-sectional study analyzed the data of 3,705 men (age 30–64 years) who participated in the 2014–2016 Korea National Health and Nutrition Examination Survey (KNHANES). SSB intake was defined as the sum of the intakes of carbonated beverages and fruit juices. Participants were categorized into study groups depending on their intake of SSBs: ≤2, 3–4, or ≥5 times per week. High CVD risk was defined as a 10-year risk of more than 10%, based on the Framingham Heart Study 10-year CVD Risk Calculator. The association between high CVD risk and SSB intake was evaluated using a multivariable-adjusted logistic regression model.
Results:
Korean men who consumed SSBs 3–4 and ≥5 times a week showed a multivariate-adjusted odds ratio of 1.49 (95% confidence interval [CI], 1.05–2.11) and 1.61 (95% CI, 0.97–2.67) for high CVD risk, respectively, compared with those who consumed SSBs ≤2 times per week. Additionally, the risk of CVD increased with the increase in the intake of SSBs (P-trend=0.01). In subgroup analysis, no association was observed between SSB intake and high CVD risk in the group with regular physical activity (P for interaction=0.01).
Conclusion
In Korean men, except those with regular physical activity, SSB intake ≥3 times a week is associated with a high risk for CVD (10-year CVD risk ≥10%).
8.Association between Consumption of Sugar-Sweetened Beverages and Risk of Cardiovascular Disease in Korean Men: Analysis Based on the Korea National Health and Nutrition Examination Survey 2014–2016
Su-Ok KIM ; Eun Mi BAE ; Ye-Na LEE ; Joung Sik SON
Korean Journal of Family Medicine 2021;42(3):212-218
Background:
This study aimed to evaluate the association between the high risk of cardiovascular disease (CVD) and the consumption of sugar-sweetened beverages (SSBs) in Korean men.
Methods:
This cross-sectional study analyzed the data of 3,705 men (age 30–64 years) who participated in the 2014–2016 Korea National Health and Nutrition Examination Survey (KNHANES). SSB intake was defined as the sum of the intakes of carbonated beverages and fruit juices. Participants were categorized into study groups depending on their intake of SSBs: ≤2, 3–4, or ≥5 times per week. High CVD risk was defined as a 10-year risk of more than 10%, based on the Framingham Heart Study 10-year CVD Risk Calculator. The association between high CVD risk and SSB intake was evaluated using a multivariable-adjusted logistic regression model.
Results:
Korean men who consumed SSBs 3–4 and ≥5 times a week showed a multivariate-adjusted odds ratio of 1.49 (95% confidence interval [CI], 1.05–2.11) and 1.61 (95% CI, 0.97–2.67) for high CVD risk, respectively, compared with those who consumed SSBs ≤2 times per week. Additionally, the risk of CVD increased with the increase in the intake of SSBs (P-trend=0.01). In subgroup analysis, no association was observed between SSB intake and high CVD risk in the group with regular physical activity (P for interaction=0.01).
Conclusion
In Korean men, except those with regular physical activity, SSB intake ≥3 times a week is associated with a high risk for CVD (10-year CVD risk ≥10%).
9.Clinical Practice Guidelines for Managing Frailty in Community-Dwelling Korean Elderly Adults in Primary Care Settings
Hyo-Sun YOU ; Yu-Jin KWON ; Sunyoung KIM ; Yang-Hyun KIM ; Ye-seul KIM ; Yonghwan KIM ; Yong-kyun ROH ; Byoungjin PARK ; Young Kyu PARK ; Chang-Hae PARK ; Joung Sik SON ; Jinyoung SHIN ; Hyun-Young SHIN ; Bumjo OH ; Jae-woo LEE ; Jae Yong SHIM ; Chang Won WON ; Ji Won YOO ; Sang-Hyun LEE ; Hee-Taik KANG ; Duk Chul LEE
Korean Journal of Family Medicine 2021;42(6):413-424
Aging has become a global problem, and the interest in healthy aging is growing. Healthy aging involves a focus on the maintenance of the function and well-being of elderly adults, rather than a specific disease. Thus, the management of frailty, which is an accumulated decline in function, is important for healthy aging. The adaptation method was used to develop clinical practice guidelines on frailty management that are applicable in primary care settings. The guidelines were developed in three phases: preparation (organization of committees and establishment of the scope of development), literature screening and evaluation (selection of the clinical practice guidelines to be adapted and evaluation of the guidelines using the Korean Appraisal of Guidelines for Research and Evaluation II tool), and confirmation of recommendations (three rounds of Delphi consensus and internal and external reviews). A total of 16 recommendations (five recommendations for diagnosis and assessment, 11 recommendations for intervention of frailty) were made through the guideline development process. These clinical practice guidelines provide overall guidance on the identification, evaluation, intervention, and monitoring of frailty, making them applicable in primary care settings. As aging and “healthy aging” become more and more important, these guidelines are also expected to increase in clinical usefulness.
10.Association of Thyroid Status with Health-Related Quality of Life in Korean Older Adults
Minjung HAN ; Seulggie CHOI ; Sarang KIM ; Ahryoung KO ; Joung Sik SON ; Sang Min PARK
Korean Journal of Family Medicine 2020;41(1):38-44
Background:
While hypothyroidism is associated with negative health effects in the general population, older adults with hypothyroidism have better physical function and comparable rates of depression and cognitive impairment relative to their euthyroid counterparts. The aim of this study was to investigate the association between thyroid status and health-related quality of life in Korean older adults.
Methods:
In this population-based cross-sectional study, 1,060 adults aged over 60 years were classified by thyroid status into four groups based on their thyroid stimulating hormone (TSH) and free T4 values: overt hypothyroid, subclinical hypothyroid, euthyroid, and subclinical hyperthyroid. The main outcome measure was self-reported health-related quality of life based on the three-level version of the EuroQol-5 dimension (EQ-5D), with utility values of -0.171 and 1.000 corresponding to the worst and best health statuses, respectively. The adjusted means of the EQ-5D three-level version utility values according to thyroid status were determined using a linear regression analysis.
Results:
In the adjusted analysis, the overt hypothyroid group showed significantly higher EQ-5D three-level version utility values than did the euthyroid group (0.998 vs. 0.908, P=0.000). In the subgroup analyses by sex, the overt hypothyroid group also showed significantly higher EQ-5D three-level version utility values for both men and women than did the euthyroid group (0.998 vs. 0.940, P=0.008; 0.983 vs. 0.882, P=0.001).
Conclusion
Asymptomatic Korean older adults aged over 60 years with TSH and free T4 values corresponding to overt hypothyroidism have better health-related quality of life than their euthyroid counterparts.

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