Prevalence, distribution, and hepatic fibrosis burden of the different subtypes of steatotic liver disease in primary care settings.

BACKGROUND AND AIM: In relation to the new umbrella terminology for steatotic liver disease (SLD), we aimed to elucidate the prevalence, distribution, and clinical characteristics of the SLD subgroups in the primary care setting. APPROACH AND RESULTS: We retrospectively collected data from 2535 individuals who underwent magnetic resonance elastography and MRI proton density fat fraction during health checkups in 5 primary care health promotion clinics. We evaluated the presence of cardiometabolic risk factors according to predefined criteria and divided all the participants according to the new SLD classification. The prevalence of SLD was 39.13% in the total cohort, and 95.77% of the SLD cases had metabolic dysfunction (one or more cardiometabolic risk factors). The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) was 29.51%, with those of metabolic dysfunction and alcohol associated steatotic liver disease (MetALD) and alcohol-associated liver disease (ALD) at 7.89% and 0.39%, respectively. According to the old criteria, the prevalence of NAFLD was 29.11%, and 95.80% of the NAFLD cases fulfilled the new criteria for MASLD. The distribution of SLD subtypes was highest for MASLD, at 75.40%, followed by MetALD at 20.06%, cryptogenic SLD at 3.33%, and ALD at 1.01%. The MetALD group had a significantly higher mean magnetic resonance elastography than the MASLD or ALD group. CONCLUSION: Almost all the patients with NAFLD met the new criteria for MASLD. The fibrosis burden of the MetALD group was higher than those of the MASLD and ALD groups.

Diagnostic Performance of Noninvasive Tests in Patients with MetALD in a Health Check-up Cohort.

BACKGROUND AND AIMS: Noninvasive tests (NITs) for liver fibrosis have been recognized for their clinical utility in metabolic dysfunction-associated steatotic liver disease (MASLD). However, their diagnostic efficacy in detecting liver fibrosis is notably reduced in patients with alcohol-related liver disease. Therefore, ascertaining the reliability of NITs in patients with MASLD with increased alcohol intake (MetALD) is essential. METHODS: In this cross-sectional study, we reviewed data from 7,918 health check-up participants who underwent both magnetic resonance elastography (MRE) and ultrasound for the diagnosis of hepatic steatosis. The participants were categorized into MASLD and MetALD groups, and the performance of fibrosis-4 (FIB-4) and NAFLD fibrosis score (NFS) were assessed. Advanced hepatic fibrosis (F3) was defined as MRE ≥ 3.6 kPa. RESULTS: The prevalence of MetALD was 5.8% in this health check-up cohort, and 1.5% of these patients exhibited advanced hepatic fibrosis. Both MetALD and MASLD displayed similar metabolic profiles and hepatic fibrosis burdens. The diagnostic performance of FIB-4 and NFS for MRE ≥ 3.6 kPa showed no noticeable differences in the area under the receiver operating characteristic values between the two groups (0.85 vs. 0.80 in FIB-4). Moreover, the sensitivity (71.4%), specificity (77.3%), and both positive (4.6%) and negative (99.4%) predictive values of NITs for MetALD closely mirrored those observed for MASLD. CONCLUSION: The newly defined MetALD exhibited a high FIB-4 performance, demonstrating reasonable sensitivity and negative predictive value for the initial screening of advanced hepatic fibrosis in MetALD. IMPACT AND IMPLICATIONS: In this cross-sectional study, data from 7,918 participants who underwent MRE were analyzed to assess the performance of fibrosis-4 (FIB-4) and nonalcoholic fatty liver disease fibrosis scores in metabolic dysfunction-associated steatotic liver disease (MASLD) and MASLD with increased alcohol intake (MetALD). We found that the newly identified MetALD group had high diagnostic accuracy with FIB-4, similar to the MASLD population. These results highlight the potential of FIB-4 as a reliable screening tool for MetALD, even when specific subgroups are considered. Therefore, FIB-4 is a valuable screening tool for identifying advanced fibrosis in the MetALD population.

Nomenclature Dilemma of Metabolic Associated Fatty Liver Disease (MAFLD): Considerable Proportions of MAFLD Are Metabolic Healthy.

BACKGROUND & AIMS: The purpose of this study was to investigate the proportion of subjects with metabolic dysfunction-associated fatty liver disease (MAFLD) and to assess the degree of hepatic fibrosis and cardiovascular risk in metabolically healthy MAFLD subjects. METHODS: A total of 6740 subjects who underwent both magnetic resonance elastography and abdominal ultrasound were included in this study. Significant (≥3.0 kPa) and advanced (≥3.6 kPa) hepatic fibrosis were evaluated by magnetic resonance elastography. The metabolic unhealthy status among subjects with MAFLD was defined as the presence of diabetes or 2 or more metabolic risk abnormalities. RESULTS: The prevalence of MAFLD among the health examination cohort was 44.5% (3002 of 6740). A total of 26.6% (800 of 3002) of MAFLD subjects were metabolically healthy (≤1 risk factors and no diabetes), and 56.3% of MAFLD subjects (1691 of 3002) did not have metabolic syndrome. Hepatic fibrosis burden and cardiovascular risk were significantly higher in the metabolic unhealthy MAFLD group than in the healthy control group. However, the prevalence of significant (5.8% vs 4.3%; P = .099) and advanced hepatic fibrosis (0.8% vs 0.7%; P = .934) did not differ between the metabolically healthy MAFLD and healthy control groups. The prevalence of carotid artery plaque in the metabolically healthy MAFLD (32.7% vs 30.7%; P = .453) group was not different from that in the healthy control group. CONCLUSIONS: Contrary to the definition of MAFLD, a non-negligible number of metabolically healthy individuals are included in the MAFLD group. The metabolic healthy MAFLD group showed a comparable fibrosis burden and prevalence of carotid artery plaque compared with the healthy control group.

Diagnostic Performance of Noninvasive Tests for Advanced Hepatic Fibrosis in Young Age Population.

BACKGROUND & AIMS: Most noninvasive tests (NITs) for hepatic fibrosis are designed for middle-aged patients with chronic liver disease. We compared the diagnostic performance of major NITs (aspartate aminotransferase-to-platelet ratio index [APRI], Fibrosis-4 index, and nonalcoholic fatty liver disease fibrosis score) for a community-based cohort. METHODS: This cross-sectional study analyzed 8775 participants who underwent magnetic resonance elastography at community health check-up centers. Advanced hepatic fibrosis (≥F3) was defined by magnetic resonance elastography thresholds of 3.6 kPa. The diagnostic performance of 3 NITs was evaluated according to the etiology of liver disease, sex, metabolic syndrome, obesity, and increased aminotransferase levels in 4 age groups. RESULTS: The APRI generally showed the best area under the receiver operating characteristic curve in patients aged 45 years or younger, and it was statistically significant in patients with chronic viral hepatitis and alcoholic fatty liver disease (P < .043). The best APRI cut-off value for detecting advanced hepatic fibrosis was 0.4, with a sensitivity and specificity of 75.8% and 73.5%, respectively, in the community-based cohort. The APRI showed balanced sensitivity and specificity across all age groups, whereas the other metrics showed low sensitivity in those aged <45 and low specificity in those >65 years. CONCLUSIONS: The APRI showed better sensitivity and negative predictive value than the Fibrosis-4 index and the nonalcoholic fatty liver disease fibrosis score in community-based populations with mixed etiology, and, thus, can be performed as the primary test in young adults (age, ≤45 y).

Antibody response after two doses of homologous or heterologous SARS-CoV-2 vaccines in healthcare workers at health promotion centers: A prospective observational study.

Assaying of anti-spike-protein receptor-binding domain (S-RBD) antibodies are used to aid evaluations of the immune statuses of individuals. The aim of this study was to determine the antibody response after two doses of homologous or heterologous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and to identify the factors affecting this response among healthcare workers (HCWs) at health promotion centers. In this prospective observational study, 1095 consenting HCWs were recruited from 16 health checkup centers and were tested at T0 (day of first dose), T1-1 (1 month after first dose), T2-0 (day of second dose), T2-1 (1 month after second dose), and T2-3 (3 months after second dose). SARS-CoV-2 antibodies were measured using a chemiluminescence microparticle immunoassay with SARS-CoV-2 IgG II Quant in the ARCHITECT system (Abbott Diagnostics). At T1-1, anti-SARS-CoV-2 S-RBD IgG levels were significantly higher in participants who received messenger RNA (mRNA) vaccines than in those who received viral vector vaccines (p < 0.001). At T2-1, anti-SARS-CoV-2 S-RBD IgG levels were about 10 times higher than at T1-1 in participants who received homologous mRNA vaccines, which decreased to a third of those at T2-3. Anti-SARS-CoV-2 S-RBD IgG levels were highest among those who received homologous mRNA vaccines, followed by heterologous mRNA viral vector vaccines and homologous viral vector vaccines at T2-3 (p < 0.001). In a multivariable linear regression analysis, being female, taking at least one mRNA vaccine, and having a history of recovery from coronavirus disease 2019 (COVID-19) were significantly associated with anti-S-RBD levels. Anti-SARS-CoV-2 S-RBD IgG levels were decreased at 3 months after two-dose vaccinations and were associated with sex, vaccine type, and COVID-19 history.

Prevalence of advanced hepatic fibrosis and comorbidity in metabolic dysfunction-associated fatty liver disease in Korea.

BACKGROUND & AIMS: There are several reports on the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD). However, the prevalence of advanced hepatic fibrosis in MAFLD is largely unknown. We aimed to evaluate the prevalence of advanced fibrosis in MAFLD. METHODS: A total of 6775 subjects from nationwide 13 health check-up centres were included in this cross-sectional study. Fatty liver was evaluated using ultrasonography. Significant (≥F2) and advanced (≥F3) hepatic fibrosis were defined by MRE thresholds of 3.0 kPa (range: 2.99-3.65 kPa) and 3.6 kPa (range: 3.4-3.9 kPa) respectively. The sex- and age-standardized prevalence of MAFLD and hepatic fibrosis was estimated. RESULTS: The sex- and age-standardized prevalence of MAFLD was 33.9%. The prevalence of obesity (BMI ≥25 kg/m2 ) in MAFLD was 71.1%, and 79.0% of obese subjects had MAFLD. The prevalence of diabetes in MAFLD was 13.3%, and 73.6% of subjects with diabetes had MAFLD. The sex- and age-standardized prevalence of significant (≥F2) and advanced hepatic fibrosis (≥F3) amongst MAFLD was 9.7% (range: 3.0-9.8%) and 3.0% (range: 2.6-4.6%) respectively. The prevalence of advanced hepatic fibrosis in overweight/obese (group I), lean (group II) and diabetic (group III) MAFLD was 2.3%, 3.1% and 9.5% respectively. CONCLUSION: The sex- and age-standardized prevalence of advanced fibrosis was 3.0% (range: 2.6-4.6%) in subjects with MAFLD.

Comparison of diagnostic performance between FIB-4 and NFS in metabolic-associated fatty liver disease era.

AIMS: Fibrosis-4 index (FIB-4) and non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) are the two most widely used non-invasive tools for screening of advanced fibrosis in subjects with NAFLD. Since metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed as a new category of fatty liver disease, we aimed to compare the diagnostic performance of FIB-4 and NFS in subjects with MAFLD and in various subgroups. METHODS: This study was designed as cross-sectional study. Data from 6775 subjects who underwent magnetic resonance elastography (MRE) and abdominal ultrasonography at the same time during a health check-up at 13 various health check-up centers were retrospectively reviewed. Advanced fibrosis was defined as an MRE value of ≥3.6 kPa. RESULTS: The area under the receiver operating characteristic curves (AUROCs) of FIB-4 and NFS for diagnosing advanced fibrosis were similar in subjects with MAFLD. However, the AUROC of NFS was lower than that of FIB-4 in the diabetic subgroup of MAFLD (0.809 in FIB-4 vs. 0.717 in NFS, p = 0.002). The performances of both FIB-4 and NFS were poor in the subgroup of MAFLD with significant alcohol intake. CONCLUSIONS: The overall diagnostic performance of FIB-4 and NFS for diagnosing advanced fibrosis did not differ among subjects with MAFLD. However, the performance of NFS was lower in the diabetes subgroup of MAFLD. The diagnostic performance of FIB-4 was better for fibrosis in various subgroups of MAFLD.

Associations of complete blood count parameters with pancreatic beta-cell function and insulin resistance in prediabetes and type 2 diabetes mellitus.

INTRODUCTION: Previous studies found controversial associations of CBC parameters with pancreatic beta-cell function (BCF) and insulin resistance (IR). The aim of this was to determine the independent associations of CBC parameters with BCF and IR in prediabetes and type 2 diabetes mellitus (T2DM). METHODS: This study selected subjects who underwent health checkups at 16 health-promotion centers in 13 Korean cities during 2021. The subjects comprised 1470 patients with normoglycemia, 1124 with prediabetes, and 396 with T2DM. BCF and IR were assessed using the homeostasis model assessment (HOMA)-ß and HOMA-IR, respectively. Correlation and multiple linear regression analyses were used to determine the correlation between CBC parameters and HOMA. RESULTS: While HOMA-IR gradually increased according to red blood cell count quartiles (1.22, 1.40, 1.47, and 1.91, in the first, second, third, and fourth quartiles, respectively; p < 0.001), there was no correlation after adjusting for waist circumference (WC) and HbA1c. The red blood cell distribution width (RDW) was associated with HOMA-ß [coefficient (ß) = 15.527, p = 0.002], but not with HOMA-IR. White blood cells (WBCs) were associated with HOMA-IR and HOMA-ß, which was stronger in HOMA-ß (ß = 0.505 vs 15.171, p = 0.002) after adjusting for WC and HbA1c. The platelet count was correlated with HOMA-IR and HOMA-ß, which only remained in HOMA-ß (ß = 15.581, p = 0.002) after adjusting for WC and HbA1c. CONCLUSION: RDW, WBC, and platelet counts were independently associated with only HOMA-ß in prediabetes and T2DM. This suggests that these CBC parameters could represent BCF in prediabetes and T2DM.

The usefulness of the estimated average glucose/fasting blood glucose ratio for pancreatic ß-cell function assessment in hyperglycemia during health checkups.

BACKGROUND: Type 2 diabetes (T2DM) is a disease marked by inadequate insulin secretion by pancreatic beta-cell function (BCF) failure and insulin resistance (IR). Assessing and managing the BCF and IR should be started early to prevent or delay the progression of the disease. The aim of this study was to determine the usefulness of the estimated average glucose (eAG)/fasting blood glucose (FBG) ratio for pancreatic BCF in hyperglycemia. METHODS: This cross-sectional study consecutively selected 10,594 subjects who underwent a health checkup at 16 health checkup centers in 13 Korean cities between 2019 and 2021. The subjects consisted of 3003 patients with normoglycemia, 3413 with impaired fasting glucose and 4178 with T2DM. The eAG was calculated using Nathan's regression equation. BCF and IR were estimated by the homeostasis model assessment (HOMA)-ß and HOMA-IR, respectively. Multivariate (adjusted) regression analysis was performed to evaluate the association between the eAG/FBG ratio and HOMA. RESULTS: The median values among FBG groups for the eAG/FBG ratio, HOMA-ß, -IR and insulin differed significantly (p < 0.001). The second-, third- and fourth-quartile groups of the eAG/FBG ratio had positive higher correlation coefficients [9.533, 10.080 and 12.021, respectively (all p < 0.001)] for HOMA-ß than the first quartile group, and higher negative coefficients for HOMA-IR [-0.696, -0.727 and -0.598, respectively (all p = 0.001)]. CONCLUSION: The eAG/FBG ratio was significantly correlated with both HOMA-ß and -IR, which suggests that eAG/FBG ratio reveals BCF and IR in hyperglycemia. Measurement of this ratio could be useful for monitoring BCF and IR in prediabetes and T2DM.

Reference interval and the role of plasma oligomeric beta amyloid in screening of risk groups for cognitive dysfunction at health checkups.

BACKGROUND: Alzheimer's disease (AD) has a prolonged preclinical stage characterized by cognitive dysfunction. Simple, reliable, and noninvasive biomarkers reflecting the pathogenesis of AD are needed for screening cognitive dysfunction in primary health care. The aims of this study were to determine (1) the potential utility of the Multimer Detection System-Oligomeric Amyloid-ß (MDS-OAß) value in cognitive assessments and (2) the reference interval (RI) of plasma MDS-OAß values in the general population. METHODS: This prospective study consecutively recruited 1,594 participants who underwent health checkups including cognitive function examination at 16 health-promotion centers in Korea between December 2020 and January 2021. The inBloodTM OAß test (PeopleBio, Gyeonggi-do, Republic of Korea) was utilized to quantify MDS-OAß values in plasma. The reference subjects were obtained among those with normal general cognition on cognitive screening tools. RIs were established according to the CLSI C28-A3 guidelines. RESULTS: The median MDS-OAß value was higher in subjects with Korean Dementia Screening Questionnaire-Cognition (KDSQ-C) scores ≥8 than in those with KDSQ-C scores of 6-7 (P = 0.013). The median MDS-OAß value was higher in subjects with Mini-Mental State Examination for Dementia Screening (MMSE-DS) scores of 21-26 than in those with MMSE-DS scores ≥27 (P = 0.011). The RI (one-side upper 95th percentile) of the MDS-OAß value was 0.80 ng/mL (95% confidence interval = 0.78-0.82) in those aged ≥50 years. CONCLUSIONS: The plasma MDS-OAß value reflects cognitive function as assessed using the KDSQ-C and MMSE-DS. RIs obtained from a large and cognitively healthy community-based sample are presented.

Subclinical Iron Deficiency in Non-Anemic Individuals: A Retrospective Analysis of Korean Health Examinees.

OBJECTIVES: Non-anemic individuals may have undetected subclinical iron deficiency (SID). The aims of this study were to determine the prevalence of SID and identify the associated factors for SID. In addition, the screening performance of red blood cell (RBC) indices for SID in health check-ups was assessed. METHODS: This study was conducted with 16,485 non-anemic health examinees (3,567 males and 12,918 females) who underwent tests for iron variables (serum iron, total iron-binding capacity, ferritin, and iron saturation) at 16 health-promotion centers in 13 cities in Korea between January 2017 and June 2018. SID was defined as a decreased ferritin level (<24 µg/L in males and <15 µg/L in females) and either a decreased serum iron level (<44 µg/dL in males and <29 µg/dL in females) or a transferrin saturation of <20%. RESULTS: The prevalence rates of SID were 0.6 and 3.3% in males and females, respectively. In terms of age and sex, SID was most prevalent in males aged ≥70 years (7.8%) and females aged 15-49 years (7.6%). There were significant differences in the hemoglobin (Hb) level, white blood cell count, platelet count, mean corpuscular volume, mean corpuscular Hb (MCH), and RBC distribution width (RDW) between the SID and non-SID groups (p < 0.001). The factors associated with SID in males were older age (odds ratio, OR, 1.069, 95% confidence interval, CI, 1.03-1.109, p = 0.004), lower Hb (OR 0.58, 95% CI 0.345-0.976, p = 0.04), lower MCH (OR 0.433, 95% CI 0.298-0.629, p < 0.001), and higher RDW (OR 1.374, 95% CI 1.001-1.887, p = 0.049), while in females they were lower body mass index (BMI; OR 0.929, 95% CI 0.895-0.963, p < 0.001) and younger age (OR 0.954, 95% CI 0.945-0.963, p < 0.001), as well as lower Hb, lower MCH, and higher RDW. The AUC for the MCH (0.877, 95% CI 0.793-0.960 in males; 0.872, 95% CI 0.853-0.890 in females) indicates that the MCH at cut-offs of 29.2 and 29.3 pg are the best discriminators of SID in males and females, respectively (p < 0.001). CONCLUSIONS: Reproductive-age females with a lower BMI and elderly males are high-risk groups for SID. MCH is a reliable RBC index for the screening of SID. For the population with defined risk factors, including females with lower BMI and elderly males, screening for SID is needed to prevent the development of anemia.

Reference interval and the role of soluble suppression of tumorigenicity 2 (sST2) in subclinical cardiac dysfunction at health checkups.

BACKGROUND: Soluble ST2 (sST2) is known to predict adverse outcomes and death in individuals with established heart failure. However, the role of sST2 testing in the general population has not been established. The aims of this study were to determine the reference interval (RI) and the clinical utility of sST2 in subclinical cardiac dysfunction in general population. METHODS: This cross-sectional study consecutively selected 41,806 general subjects at health checkups who underwent echocardiography and sST2 testing at 16 health promotion centers in 13 Korean cities. The reference subjects were obtained among those with normal findings in echocardiography. Sex-specific RIs were established according to the CLSI C28-A3 guidelines. sST2 was measured using immunoassay with the Presage ST2 assay (Critical Diagnostics). RESULTS: In the general subjects, age, sex, BMI, systolic blood pressure, blood glucose, creatinine, liver function, and triglycerides were associated with the sST2 levels. The RI for sST2 was higher in males (≤49.6 ng/mL, 95% CI = 48.5-51.5) than in females (≤44.5 ng/mL, 95% CI = 43.5-45.6) and higher in subjects aged < 40 years than ≥ 40 years in both sexes. The sST2 levels were 29.1 ± 10.7 (mean ± SD) and 29.1 ± 14.4 ng/mL in the groups with normal cardiac function and subclinical cardiac dysfunction, respectively. The sST2 level was not associated with subclinical cardiac dysfunction (odd ratio = 1.002, P = .13). CONCLUSIONS: RIs obtained from a large and echocardiography-proven healthy community-based sample are presented. Subclinical cardiac dysfunction was associated with older age, male sex, and metabolic factors but not with the sST2 level.

Diagnostic performance of Mac-2 binding protein glycosylation isomer (M2BPGi) in screening liver fibrosis in health checkups.

BACKGROUND: Mild-to-moderate fibrosis is rarely diagnosed because the disease is asymptomatic in the early stage. The serum level of Mac-2 binding protein glycosylation isomer (M2BPGi) has been found to increase with the severity of liver fibrosis. The aim of this study was to determine the diagnostic performance of M2BPGi in screening liver fibrosis using magnetic resonance elastography (MRE) as a reference standard and to compare it with using the aspartate aminotransferase-to-platelet ratio (APRI) and the Fibrosis-4 index (FIB-4) in health checkups. METHODS: This cross-sectional study consecutively selected subjects at health examinations who underwent MRE and M2BPGi testing at eight health promotion centers in Korea between January and September 2019. The serum M2BPGi level was measured using the chemiluminescence enzyme immunoassay method. The measured levels were indexed using the cutoff index (COI). COI values of M2BPGi were compared with the MRE results. RESULTS: The median (interquartile) values of COI for fibrosis stages F0 (normal liver stiffness), F1 (mild fibrosis), F2 (significant fibrosis), and ≥F3 (advanced fibrosis) were 0.49 (0.34-0.61), 0.48 (0.38-0.68), 0.64 (0.43-1.03), and 1.01 (0.75-1.77), respectively (P < .0001). The AUCs of the COI for the screening of fibrosis stage ≥F1, ≥F2, and ≥F3 were 0.591, 0.698, and 0.853, respectively. Using a threshold of 0.75 for COI to exclude advanced fibrosis had a sensitivity, specificity, and negative predictive value of 80.0%, 77.9%, and 98.9%, respectively. The AUC for excluding advanced fibrosis was better for M2BPGi than for FIB-4 and APRI. CONCLUSION: Serum M2BPGi was useful for screening significant and advanced fibrosis in health checkups.

Changes in nonalcoholic fatty liver disease and M2BPGi due to lifestyle intervention in primary healthcare.

BACKGROUND: A healthy lifestyle is the most important method for managing nonalcoholic fatty liver disease (NAFLD). Mac-2-binding protein glycosylated isomer (M2BPGi) has been suggested as a biomarker for NAFLD. This study aimed to determine the efficacy of personalized lifestyle interventions on NAFLD remission. METHODS: This single-arm intervention study recruited participants with NAFLD who underwent health checkups at seven health-promotion centers in five South Korean cities. Fatty liver diagnosis was based on ultrasonography (US). The 109 individuals were recruited for personalized lifestyle interventions of hypocaloric diets and exercise. The participants attended the lifestyle intervention programs once per month for the first 3 months, and once every 3 months for the subsequent 6 months. In addition to sessions through center visits, phone-based intervention and self-monitoring at 4-, 5-, 7-, and 8-month were provided during the 9-month intervention period. And phone-based self-monitoring were also provided monthly during the 3-month follow-up period. The primary outcome was NAFLD remission at month 12 as measured on US and magnetic resonance elastography. The secondary outcomes were the changes in metabolic factors and M2BPGi. RESULTS: The 108 individuals (62 males and 46 females; age 51.1±12.4 years, mean±standard deviation) were finally analyzed after the 12month intervention. Body mass index, waist circumference (WC), blood pressure, blood lipids (total cholesterol, triglycerides, and HDL-C), and fasting blood sugar levels were improved relative to baseline (all P<0.05). Fatty liver at or above the moderate grade according to US was decreased at month 12 relative to baseline (67.6% vs 50.9%) (P = 0.002). M2BPGi levels decreased during the 12-month study period (P<0.001). M2BPGi levels were moderately correlated with hepatic fat fraction by magnetic resonance imaging (r = 0.33, P = 0.05). WC (OR = 0.82, 95% CI = 0.67-1.00, P = 0.05) and HDL-C (OR = 1.17, 95% CI = 1.03-1.32, P = 0.014) were associated with remission of fatty liver in the multivariate analysis. CONCLUSION: The personalized lifestyle intervention was effective in improving fatty liver and metabolic factors, but not hepatic stiffness, in NAFLD. TRIAL REGISTRATION: ICTRP, cris.nih.go.kr (KCT0006380).

Vitamin D Status and Reference Intervals Measured by Liquid Chromatography-Tandem Mass Spectrometry for the Early Adulthood to Geriatric Ages in a South Korean Population during 2017-2022.

This study aimed to describe the latest 25-hydroxyvitamin D (25(OH)D) status of the South Korean population aged ≥ 20 years using 25(OH)D concentrations measured by liquid chromatography-tandem mass spectrometry and to determine the factors associated with total 25(OH)D concentrations. This cross-sectional, retrospective study consecutively selected 119,335 subjects with a median age of 57 (20-101) years who underwent health checkups among 13 Korean cities during 2017-2022. The total 25(OH)D concentration was 54.5 ± 24.0 nmol/L (mean ± SD). The 7.6%, 47.5%, and 82.9% of participants had 25(OH)D less than 25, 50, and 75 nmol/L, respectively. The prevalence of 25(OH)D deficiency (<25 nmol/L) was higher in females than in males (8.9% vs. 6.1%) and varied between age groups, decreasing in older subjects. Those aged 20-29 years had the highest prevalence of 25(OH)D deficiency (23.0% in females and 20.1% in males), which also varied between cities. In the adjusted model, female sex, older age, summer and autumn seasons, lower body mass index (<25 kg/m2), and lower high-sensitivity C-reactive protein concentration (<1 mg/L) were associated with higher total 25(OH)D concentrations. This study could provide an exact understanding of the status of vitamin D and help devise strategies to prevent vitamin D deficiency among the Korean population.

Reference intervals of cell population data parameters in Sysmex XN-Series and its patterns of changes from early adulthood to geriatric ages in South Korea.

INTRODUCTION: Cell population data (CPD) parameters may be putative biomarkers for the screening of various diseases including some infections and myelodysplastic syndrome. This study aimed to establish the age- and sex-specific reference intervals (RIs) for the CPD parameters in the Korean population. METHODS: The reference population for the RIs of CPD parameters comprised 124 856 subjects aged 20-99 years. CPD parameters were obtained from Sysmex XN-2000 (Kobe, Japan) datasets from 17 health promotion centers in 13 South Korean cities. We determined significant partitions for age and sex, and calculated RIs according to Clinical and Laboratory Standards Institute C28-A3 guidelines. RESULTS: The side scattered light intensity in the neutrophil area and the lymphocyte area did not require sex-related partitioning except in those over the age of 50, among whom the lower limit (LL) and upper limit (UL) were lower in females. However, the side scattered light distribution width in the lymphocyte area required age- and sex-related partitioning, in which LL and UL were higher in females. The LL and UL of the fluorescent light distribution width were higher in males in the neutrophil area and higher in females in the lymphocyte area, but age-related partitioning was not required. The forward scattered light intensity in the neutrophil area, lymphocyte area, and monocyte area did not require age-related partitioning in males. CONCLUSION: This study has determined comprehensive age- and sex-specific RIs for CPD parameters, which could help to prove the clinical significance of these parameters in the Sysmex XN-2000.

Establishment and validation of reference intervals for tumor markers (AFP, CEA, CA19-9, CA15-3, CA125, PSA, HE4, Cyfra 21-1, and ProGRP) in primary care centers in Korea: A cross-sectional retrospective study.

Background and Aims: The reference interval (RI) for a tumor marker may vary between populations, detection systems, and the methods used to obtain their values. The aims of this study were to establish age- and sex-specific RIs for the following nine common tumor markers and to validate the established RIs in Korean adults: alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), cancer antigen (CA) 19-9, CA15-3, CA125, Human epididymis protein 4 (HE4), total prostate specific antigen, cytokeratin fragment (Cyfra) 21-1, and progastrin-releasing peptide (ProGRP). Methods: This cross-sectional study consecutively selected 214,159 individuals (aged 18-98 years) who underwent health checkups at 16 health-promotion centers in 13 Korean cities. Finally, 62,752 examinees were used to establish the RIs after removing outliers. RIs were established using an indirect method according to the CLSI EP28-A3C guideline. The established RIs were validated by calculating the proportion of individuals outside each RI. Results: Sex-related differences were observed for AFP, CEA, CA19-9, Cyfra 21-1, and ProGRP (p < 0.05): AFP, CEA and Cyfra 21-1 were higher in males, and CA19-9 and proGRP were higher in females. Most of the tumor markers except CA15-3 and CA125 increased with age: CA125 decreased at ≥50 years of age (p < 0.05), while CA15-3 did not vary with age. Less than 5% of subjects were outside all RIs (the 2.5th and 97.5th percentiles) established in the present study. Meanwhile, less than 3% of the healthy reference subjects fell outside the current and manufacturers' RIs of all tumor markers except Cyfra 21-1. Conclusion: This study has determined age- and sex-specific RIs for nine common tumor markers in the healthy Korean population, which could be useful for clinicians making clinical decisions and assessments.

SARS-CoV-2 Antibody Response and Sustainability after a Third Dose of BNT162b2 in Healthcare Workers at Health Promotion Centers.

The aim of this study was to determine the antibody response and the sustainability of immunogenicity after a third dose of BNT162b2 (BNT) in homologous [ChAdOx1 (ChAd)/ChAd, BNT/BNT, and mRNA-1273 (Moderna)/Moderna] and heterologous (ChAd/BNT) vaccinations of two primary doses with different schemes. This prospective observational study recruited consenting healthcare workers from 16 health checkup centers in 13 Korean cities. Three-point blood tests were analyzed as the antibody response after the third vaccination: T3-1 (1 month after the third dose), T3-3 (3 months after the third dose), and T3-4-10 (4-10 months after the third dose). SARS-CoV-2 antibodies were measured using a chemiluminescence microparticle immunoassay with SARS-CoV-2 IgG II Quant in the ARCHITECT system (Abbott Diagnostics). The antibody levels were significantly higher in the Moderna /Moderna and BNT/BNT groups than in the ChAd/ ChAd and ChAd/BNT groups (p < 0.05) at T3-1. At T3-3, antibody levels had decreased by 29.1% in the BNT/BNT group and by 45.3% in the ChAd/ChAd group compared with the antibody levels at T3-1. The anti-SARS-CoV-2 S-RBD IgG levels at T3-1 were significantly associated with having received mRNA vaccines as the two primary doses (p < 0.001). The third dose of BNT induced an increased humoral immune response in various vaccination schemes, which was more prominent for the two primary doses of homologous mRNA vaccines. However, this immunogenicity decreased within 3-10 months after the third dose. These results suggest that another booster dose (a fourth dose), which would be able to counteract SARS-CoV-2 variants, is needed.