Diagnostic performance of non-invasive tests in patients with MetALD in a health check-up cohort.

BACKGROUND & AIMS: Non-invasive 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 moderate 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 index (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: FIB-4 performed well for the initial screening of advanced hepatic fibrosis in MetALD, demonstrating reasonable sensitivity and negative predictive values. 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 non-alcoholic fatty liver disease fibrosis scores in metabolic dysfunction-associated steatotic liver disease (MASLD) and MASLD with moderate alcohol intake (MetALD). We found that FIB-4 had high diagnostic accuracy in the newly identified MetALD group, similar to that in 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.

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.

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).

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.

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 the fibrosis-4 index and the NAFLD fibrosis score for screening at-risk individuals in a health check-up setting.

BACKGROUND: The fibrosis-4 index (FIB-4) and the NAFLD fibrosis score (NFS) have been used as noninvasive screening methods for advanced fibrosis in patients with NAFLD. However, their diagnostic performance has not been evaluated in at-risk individuals regardless of hepatic steatosis. This study evaluated the performance of the FIB-4 and NFS in at-risk groups of health check-up examinees at mass screening centers. METHODS: This retrospective, cross-sectional study included 8545 participants who underwent voluntary magnetic resonance elastography at a discounted fee during their regular health check-ups at 13 mass screening centers nationwide. The at-risk group was defined as those with any of the following conditions: NAFLD, 2 or more metabolic abnormalities, diabetes mellitus, or abnormal aminotransferase levels. A magnetic resonance elastography cutoff of ≥3.6 kPa was used to define conventional advanced fibrosis. RESULTS: According to the proposed criteria, the proportion of at-risk individuals was 67.4%-80.2% in the health check-up cohort without viral or alcohol-associated liver disease. The prevalence of individuals with advanced hepatic fibrosis in each at-risk group was ~2.3%-2.8% according to various criteria. It was higher in patients without NAFLD than in those with NAFLD. A total of 28.2%-39.6% of those in each at-risk group did not show hepatic steatosis on ultrasonography. The performance of FIB-4 for advanced fibrosis in the at-risk group was comparable with that in the NAFLD group. FIB-4 showed a better area under the receiver operating characteristic curve and sensitivity than NFS in the at-risk group. CONCLUSIONS: FIB-4 demonstrated superior performance compared with the NFS, and its performance in at-risk individuals was similar to that observed for patients with NAFLD.

Prevalence of head louse infestation among primary schoolchildren in the Republic of Korea: nationwide observation of trends in 2011-2019.

Head louse infestation is a significant public health problem across the world, particularly among preschool and primary schoolchildren. This study investigated the trends of head louse infestation in the Republic of Korea over a 9-year period (2011-2019), targeting primary schoolchildren in 3 areas of Seoul, 4 other large cities, and 9 provinces. A survey was administered annually by the health staff of each regional office (n= 16) of the Korea Association of Health Promotion (KAHP). The branch offices of KAHP examined a total of 51,508 primary schoolchildren, comprising 26,532 boys and 24,976 girls. Over the 9-year survey, a total of 1,107 (2.1%) schoolchildren tested positive for adults and/or nits of Pediculus humanus capitis. The prevalence was 2.8% (133/4,727) in 2011-2012 and gradually decreased to 0.8% (49/6,461) in 2019 (P< 0.05). Head lice were found more frequently in girls (3.0%; 746/24,976) than in boys (1.4%; 361/26,532) (P< 0.05). In terms of geographic localities, the highest infestation rate, 4.7% (average prevalence over 9 years), was observed in southern Seoul (Gangnam branch of KAHP), whereas the lowest infestation rate, 0.7%, was seen in Gyeongsang (north and south provinces) and western Seoul. Although the prevalence decreased significantly during the 9-year period, head louse infestation remains a health and hygiene issue among primary schoolchildren in the Republic of Korea. Regular surveys along with health education are needed to further improve children's hair hygiene.

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).

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.

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.