Incidences of new hepatitis B infection and anti-hepatitis B core-negative occult hepatitis B infection among Japanese blood donors in relation to anti-hepatitis B surface antigen levels.

A transfusion-transmitted hepatitis B virus (HBV) infection caused by blood only positive for anti-hepatitis B surface antigen (anti-HBs) was reported. Occult HBV infection (OBI) with sole anti-HBs among blood donors is an issue. The incidence of HBV infection among repeat blood donors was investigated with a detailed HBV infection phase, focusing on the influence of anti-HBs level. This study followed 3 435 653 donors for HBV DNA conversion over 4 years and 9 months. Infection phase was determined based on marker changes over DNA conversion. This study identified 115 hepatitis B surface antigen (HBsAg) conversions, 72 DNA-only conversions, and 15 DNA plus anti-hepatitis B core (anti-HBc) conversions among donors all negative for HBV DNA, HBsAg, and anti-HBc. Total incidence was 2.38/100 000 person-years (PY). None of these 202 new HBV infections arose in the group with anti-HBs titer ≥ 10 mIU/mL. In total, 30 anti-HBc-negative OBIs were identified (incidence; 0.35/100 000 PY); 7 showed typical secondary anti-HBs response, and 23 showed stable anti-HBc and anti-HBs levels at DNA conversion. The HBV infection-protective ability of anti-HBs ≥ 10 mIU/mL was reinforced. In addition to new infections, the blood donor population includes anti-HBc-positive- and negative OBI with immune reactions or abortive HBV infection.

Identification of risk groups for advanced liver fibrosis in the general population using the Fibrosis-3 index.

Background and Aim: We conducted a study using the Fibrosis-3 (FIB-3) index, which is the established age-independent index of fibrosis in nonviral liver disease and addresses the limitations of the FIB-4 index in older age group, to assess the liver fibrosis risk among diverse demographic groups in the general population. Methods: We analyzed 31 327 individuals who underwent health examinations between 2013 and 2020 and investigated the distribution of the FIB-3 index by age group. In addition, we examined the age distribution of the FIB-3 index stratified by background factors, such as sex, body mass index (BMI), alcohol consumption habits, and the presence or absence of fatty liver. Results: In terms of age-specific distribution, the FIB-3 index remained below 1.5 in >90% of cases until the age of 50 years but exceeded 1.5 beyond the age of 50 years, in approximately 30% among those aged 70 years. Notably, the FIB-3 index above 31 years old was significantly higher in men than in women. Among the different BMI categories, individuals with BMI < 18.5 exhibited the highest prevalence of fibrosis. Habitual drinkers had a higher proportion with FIB-3. index ≥1.5, and some had FIB-3 index ≥2.5, raising the suspicion of advanced hepatic fibrosis. No distinct association was identified between the FIB-3 index and the presence of fatty liver. Conclusions: The FIB-3 index was useful for identifying cases of advancing hepatic fibrosis in a health checkup population. Liver fibrosis progresses with age in the general population, especially among men, those with low BMI, and habitual drinkers.

Development of a unit conversion tool for five quantitative anti-spike assays and agreement analysis of three qualitative anti-nucleocapsid assays for SARS-CoV-2.

Commercially available assays for measuring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike (S) or anti-nucleocapsid (N) antibodies differ in units, making results comparisons challenging. This study aimed to develop conversion equations between five quantitative anti-S antibody tests and to assess the agreement over time between three qualitative anti-N antibody tests. Blood samples from 24 216 vaccinated healthcare workers in Hiroshima Prefecture, Japan, were analyzed for anti-S antibodies using five quantitative tests (Abbott, Fujirebio, Ortho, Sysmex, Roche) and for anti-N antibodies using three qualitative tests (Abbott, Sysmex, Roche). Geometric mean regression was performed to establish equations for converting measured values between the five quantitative tests. Fleiss κ statistic was used to assess the agreement between the three qualitative tests. A strong correlation (Pearson's coefficient r > 0.9) was found for each pair of the five quantitative tests measuring anti-S antibodies, enabling the development of equations to convert values between each pair. Using these equations, which are based on the original output unit of each test, values obtained from one test can be transformed to be equivalent to the corresponding values in another test. For the three tests for anti-N antibodies, the agreement was substantial in the total sample (Fleiss' κ, 0.74) and moderate among those with self-reported past coronavirus disease 2019 (COVID-19) infection (Fleiss' κ, 0.39). The agreement decreased with time after infection. Reduced agreement between anti-N antibodies tests over time suggests caution in comparing seroepidemiological studies of COVID-19 exposure based on anti-N antibodies measurement. The findings could help improve antibody measurement systems and inform public health decision-makers.

Knowledge of hepatitis B infection, hepatitis B vaccine, and vaccination status with its associated factors among healthcare workers in Kampot and Kep Provinces, Cambodia.

BACKGROUND: Healthcare Workers (HCWs) are susceptible to hepatitis B virus (HBV) infection and are advised to receive vaccination. However, vaccination rates remain low in developing countries. There is little data concerning Hepatitis B (HepB) vaccination and information regarding HBV knowledge among HCWs in Cambodia. This study aimed to evaluate the knowledge of HBV infection, HepB vaccine, and vaccination status with its associated factors among HCWs in Cambodia. METHODS: A Cross-sectional study was conducted among HCWs in Kampot and Kep Provinces, Cambodia, from September to October 2023 using a questionnaire survey. A total of 261 HCWs were recruited from 1,309 individuals working in all 83 health facilities using systematic random sampling methods. Statistical analyses including the χ2-test and multivariate logistic regression were conducted to identify factors associated with vaccination among the participants. RESULTS: Among 259 participants, 62.9% showed good knowledge of HBV infection, and 65.6% demonstrated good knowledge of the HepB vaccine. 59.8% of the participants had received the HepB vaccine, while 40.2% remained unvaccinated. Analysis showed that HCWs working at Provincial Health Department/Operational Districts and Provincial Referral Hospital/Referral Hospitals were more likely to be vaccinated compared to those at Health Centers [AOR = 6.5; CI = 1.1-39.5, p = 0.0403; AOR = 2.8, CI = 1.0-7.8, p = 0.0412], respectively. Furthermore, individuals with good knowledge of the HBV infection and vaccine were more likely to receive the vaccine compared to those with inadequate knowledge [AOR = 6.3; CI = 3.3-12.3, p < .0001; AOR = 3.7, CI = 1.9-7.4, p = 0.0001], respectively. Within the unvaccinated HCWs, 32% reported high vaccine costs as a barrier, 33% mentioned workplace vaccine was not for adults, and 59% reported insufficient education on adult HepB vaccination. CONCLUSIONS: The HepB vaccination coverage among HCWs is at 59.8%, which is below the World Health Organization's (WHO) recommendation rate of 100%. Knowledge of HBV infection and HepB vaccine were good predictive factors for vaccination. The high cost of vaccine, workplace vaccine not for adults, and insufficient education on adult vaccination were found as barriers to vaccination. This study underscores the importance of providing education to HCWs on HBV infection and the HepB vaccine. Furthermore, it highlights the need for a policy that ensures free vaccination for HCWs.

Real-time observation of a metal complex-driven reaction intermediate using a porous protein crystal and serial femtosecond crystallography.

Determining short-lived intermediate structures in chemical reactions is challenging. Although ultrafast spectroscopic methods can detect the formation of transient intermediates, real-space structures cannot be determined directly from such studies. Time-resolved serial femtosecond crystallography (TR-SFX) has recently proven to be a powerful method for capturing molecular changes in proteins on femtosecond timescales. However, the methodology has been mostly applied to natural proteins/enzymes and limited to reactions promoted by synthetic molecules due to structure determination challenges. This work demonstrates the applicability of TR-SFX for investigations of chemical reaction mechanisms of synthetic metal complexes. We fix a light-induced CO-releasing Mn(CO)3 reaction center in porous hen egg white lysozyme (HEWL) microcrystals. By controlling light exposure and time, we capture the real-time formation of Mn-carbonyl intermediates during the CO release reaction. The asymmetric protein environment is found to influence the order of CO release. The experimentally-observed reaction path agrees with quantum mechanical calculations. Therefore, our demonstration offers a new approach to visualize atomic-level reactions of small molecules using TR-SFX with real-space structure determination. This advance holds the potential to facilitate design of artificial metalloenzymes with precise mechanisms, empowering design, control and development of innovative reactions.

A nation-wide medical record database study: Value of hepatitis B surface antigen loss in chronic hepatitis B patients in Japan.

AIM: Hepatitis B surface antigen (HBsAg) seroclearance is considered to be one of the best surrogate endpoints of functional cure for hepatitis B virus (HBV) infection. However, evidence regarding the relationship between achieving HBsAg seroclearance or a low baseline HBsAg level, and long-term clinical outcomes in Japanese patients with chronic HBV infection remains to be confirmed in a real-world setting. METHODS: A retrospective observational cohort study was performed with an electronic medical record database, including data from 230 hospitals across Japan. Chronic HBV infection was defined as two consecutive, positive HBsAg laboratory measurements for HBV infection. The date of the second positive was used as a baseline to identify subsequent HBsAg seroclearance and liver disease progression. RESULTS: In the database, 2523 patients with chronic HBV infection were identified as the chronic hepatitis B (CHB) cohort. Among the CHB cohort with an average observational period of 5.19 ± 3.87 years, 202 patients (8%) achieved HBsAg seroclearance after baseline. They had a lower risk of developing hepatocellular carcinoma (HCC) (adjusted hazard ratio [aHR] 0.206, p < 0.01) and cirrhosis (aHR 0.361, p < 0.01). When the CHB cohort was stratified into two groups based on baseline HBsAg levels (<100 IU/mL and ≥100 IU/mL), patients with a lower baseline level of HBsAg (<100 IU/mL) had a lower risk of developing liver disease (HCC aHR 0.600, p < 0.01; cirrhosis aHR 0.618, p < 0.05). CONCLUSIONS: These results confirm the clinical significance of HBsAg seroclearance and low HBsAg level at baseline with respect to long-term outcomes of patients with CHB in the Japanese population.

Systematic review and meta-analysis of hepatitis E seroprevalence in Southeast Asia: a comprehensive assessment of epidemiological patterns.

The burden of hepatitis E in Southeast Asia is substantial, influenced by its distinct socio-economic and environmental factors, as well as variations in healthcare systems. The aim of this study was to assess the pooled seroprevalence of hepatitis E across countries within the Southeast Asian region by the UN division.The study analyzed 66 papers across PubMed, Web of Science, and Scopus databases, encompassing data from of 44,850 individuals focusing on anti-HEV seroprevalence. The investigation spanned nine countries, excluding Brunei and East Timor due to lack of data. The pooled prevalence of anti-HEV IgG was determined to be 21.03%, with the highest prevalence observed in Myanmar (33.46%) and the lowest in Malaysia (5.93%). IgM prevalence was highest in Indonesia (12.43%) and lowest in Malaysia (0.91%). The study stratified populations into high-risk (farm workers, chronic patients) and low-risk groups (general population, blood donors, pregnant women, hospital patients). It revealed a higher IgG-28.9%, IgM-4.42% prevalence in the former group, while the latter group exhibited figures of 17.86% and 3.15%, respectively, indicating occupational and health-related vulnerabilities to HEV.A temporal analysis (1987-2023), indicated an upward trend in both IgG and IgM prevalence, suggesting an escalating HEV burden.These findings contribute to a better understanding of HEV seroprevalence in Southeast Asia, shedding light on important public health implications and suggesting directions for further research and intervention strategies.Key pointsResearch QuestionInvestigate the seroprevalence of hepatitis E virus (HEV) in Southeast Asian countries focusing on different patterns, timelines, and population cohorts.FindingsSporadic Transmission of IgG and IgM Prevalence:• Pooled anti-HEV IgG prevalence: 21.03%• Pooled anti-HEV IgM prevalence: 3.49%Seroprevalence among specific groups:High-risk group (farm workers and chronic patients):• anti-HEV IgG: 28.9%• anti-HEV IgM: 4.42%Low-risk group (general population, blood donors, pregnant women, hospital patients):• anti-HEV IgG: 17.86%• anti-HEV IgM: 3.15%Temporal Seroprevalence of HEV:Anti-HEV IgG prevalence increased over decades (1987-1999; 2000-2010; 2011-2023): 12.47%, 18.43%, 29.17% as an anti-HEV IgM prevalence: 1.92%, 2.44%, 5.27%ImportanceProvides a comprehensive overview of HEV seroprevalence in Southeast Asia.Highlights variation in seroprevalence among different population groups.Reveals increasing trend in HEV seroprevalence over the years.Distinguishes between sporadic and epidemic cases for a better understanding of transmission dynamics.

Severe hepatic steatosis promotes increased liver stiffness in the early stages of metabolic dysfunction-associated steatotic liver disease.

BACKGROUND & AIMS: The predictors of progression from steatosis to more advanced stages of metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear. We evaluated the association between the quantity of hepatic steatosis and longitudinal changes in liver stiffness measurements (LSMs) using magnetic resonance elastography (MRE) in patients with MASLD. METHODS: We retrospectively analysed patients with MASLD who underwent at least two serial MRE and magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) examinations at least 1 year apart. Fine-Gray competitive proportional hazard regression was used to identify LSM progression and regression factors. RESULTS: A total of 471 patients were enrolled. Factors linked to LSM progression were steatosis grade 3 (MRI-PDFF ≥17.1%, adjusted hazard ratio [aHR] 2.597; 95% confidence interval [CI] 1.483-4.547) and albumin-bilirubin grade 2 or 3 (aHR 2.790; 95% CI 1.284-6.091), while the only factor linked to LSM regression was % decrease rate of MRI-PDFF ≥5% (aHR 2.781; 95% CI 1.584-4.883). Steatosis grade 3 correlated with a higher incidence rate of LSM progression than steatosis grade 1 (MRI-PDFF <11.3%) in patients with LSM stage 0 (<2.5 kilopascal [kPa]), and a % annual decrease rate of MRI-PDFF ≥5% correlated with a higher incidence rate of LSM regression than that of MRI-PDFF >-5% and <5% in patients with LSM stage 1 or 2-4 (≥2.5 kPa). CONCLUSIONS: Severe hepatic steatosis was linked to significant LSM progression in patients with MASLD and low LSM (<2.5 kPa).

Epidemiological assessment of hepatitis E virus infection among 1565 pregnant women in Siem Reap, Cambodia using an in-house double antigen sandwich ELISA.

AIM: This study investigated hepatitis E virus (HEV) prevalence among pregnant women in Siem Reap, Cambodia, by developing a cost-effective, user-friendly in-house enzyme-linked immunosorbent assay (ELISA) for detecting total anti-HEV immunoglobulins (Ig). METHODS: The in-house ELISA was designed for large-scale screening in resource-limited settings. Its performance was benchmarked against two commercial tests: the Anti-HEV IgG EIA (Institute of Immunology, Co. Ltd) and the Anti-HEV IgG RecomLine LIA (Mikrogen). The in-house ELISA demonstrated a sensitivity of 76% and 71.4%, and a specificity of 94.1% and 98.6%, against the two commercial tests, respectively, with overall agreement rates of 92.4% and 94.3%. RESULTS: Among 1565 tested pregnant women, 11.6% were anti-HEV positive. Prevalence increased with age, particularly in women aged 35-40 years and over 40 years. No significant associations were found with education, number of children, family size, or history of blood transfusion and surgery, except for the occupation of the family head as a public officer. Of the total anti-HEV positive women, 22.7% had anti-HEV IgM, indicating recent or ongoing infection. CONCLUSION: The study concluded that the in-house ELISA is a viable option for HEV screening in regions with limited resources due to its high accuracy and cost-effectiveness. It is particularly suitable for large-scale studies and public health interventions in areas where HEV is endemic and poses a significant risk to pregnant women.

Effectiveness of COVID-19 mRNA vaccine in preventing infection against Omicron strain: Findings from the Hiroshima Prefecture COVID-19 version J-SPEED for PCR center.

BACKGROUND AND PURPOSE: Despite the widespread adoption of various preventive measures since the spread of COVID-19, there remains a lack of consensus on universally acknowledged best practices. However, the significance of vaccination has risen to prominence as a paramount preventive strategy. Numerous investigations have demonstrated vaccine effectiveness against the omicron strain in severe disease and symptomatic disease, however, the scope of research pertaining to vaccine effectiveness in preventing infection is presently limited. Therefore, the current study aimed to evaluate COVID-19 mRNA (Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273) vaccine effectiveness in preventing infection. METHODS: We conducted a test-negative case-control study using a dataset of 117,335 individuals. These data were collected through the COVID-19 J-SPEED form in the PCR center at Hiroshima Prefecture, Japan from 1 February to 17 March 2022. We estimated propensity score matching for vaccine status based on participants' demographic characteristics. Subsequently, odds ratio was calculated from logistic regression to determine the association between vaccination status and test positivity rate adjusting for symptoms, exposure to close contact, and previous infection history. Vaccine effectiveness was defined as (1 -aORs) ×100%. RESULTS: The PCR test positivity rates were 7.9%, 4.5%, and 2.8% for the non-vaccinated (non-vaccinated, vaccinated with a single dose, and vaccinated with two doses less than 14 days ago), vaccinated with two doses (vaccinated over 14 days ago), and three doses, respectively. In unadjusted and adjusted analyses, vaccine effectiveness of two doses against infection were 38.5% (95% confidence interval [CI]: 32.8%-43.8%) and 34.7% (95%CI: 28.4%-40.4%), respectively, compared to non-vaccinated group. Vaccine effectiveness of three doses were 33.8% (95%CI: 25.0%-41.5%) and 26.4% (95%CI: 16.4%-35.2%), respectively, compared to those vaccinated with two doses. CONCLUSIONS: These results illustrate the protective effect of mRNA vaccines against Omicron strain infections and emphasize the significance of completing the suggested vaccination schedule.

Potential Risk Factors to COVID-19 Severity: Comparison of SARS-CoV-2 Delta- and Omicron-Dominant Periods.

BACKGROUND: Continued study of risk factors can inform future pandemic preparedness and response. We aimed to determine the potential risk factors of COVID-19 severity among patients admitted to the hospital during the Delta- and Omicron-dominant periods. METHODS: We utilized the J-SPEED-style COVID-19 Hospital version, a pre-administered questionnaire, to collect data from hospitals in Hiroshima Prefecture between 8 August 2021 and 19 April 2022. RESULTS: During the Delta-dominant period, patients aged over 65 (OR = 2.59, 95% CI = 1.75-3.84), males (OR = 1.42, 95% CI = 1.12-1.81) and with BMI exceeding 25 (OR = 1.99, 95% CI = 1.57-2.52), diabetes (OR = 2.03, 95% CI = 1.40-2.95), and those with fewer than two doses of vaccine (OR = 2.39, 95% CI = 1.46-3.91) were at a greater risk of severe COVID-19 compared to those without these risk factors. During the Omicron-dominant period, significantly greater severity was observed among patients over 65 years old (OR = 3.89, 95% CI = 2.95-5.12), males (OR = 1.76, 95% CI = 1.40-2.21), those with high blood pressure (OR = 1.30, 95% CI = 1.02-1.65), and mental disorder (OR = 2.22, 95% CI = 1.69-2.92) compared to patients without these risks. CONCLUSIONS: Our findings indicate that risk factors vary across different SARS-CoV-2 variants. Examining variant-specific risk factors for COVID-19 severity can aid policymakers, public health specialists, and clinicians in prioritizing screening, treatment, and vaccination efforts, especially during potential healthcare resource shortages.

Advanced fibrosis leads to overestimation of steatosis with quantitative ultrasound in individuals without hepatic steatosis.

PURPOSE: The effect of hepatic fibrosis stage on quantitative ultrasound based on the attenuation coefficient (AC) for liver lipid quantification is controversial. The objective of this study was to determine how the degree of fibrosis assessed by magnetic resonance (MR) elastography affects AC based on the ultrasound-guided attenuation parameter according to the grade of hepatic steatosis, using magnetic resonance imaging (MRI)-derived proton density fat fraction (MRIderived PDFF) as the reference standard. METHODS: Between February 2020 and April 2021, 982 patients with chronic liver disease who underwent AC and MRI-derived PDFF measurement as well as MR elastography were enrolled. Multiple regression was used to investigate whether AC was affected by the degree of liver stiffness. RESULTS: AC increased as liver stiffness progressed in 344 patients without hepatic steatosis (P=0.009). In multivariable analysis, AC was positively correlated with skin-capsule distance (P<0.001), MR elastography value (P=0.037), and MRI-derived PDFF (P<0.001) in patients without hepatic steatosis. In 52 of 982 patients (5%), the correlation between AC and MRIderived PDFF fell outside the 95% confidence interval for the regression line slope. Patients with MRI-derived PDFF lower than their AC (n=36) had higher fibrosis-4 scores, albumin-bilirubin scores, and MR elastography values than patients with MRI-derived PDFF greater than their AC (n=16; P=0.018, P=0.001, and P=0.011, respectively). CONCLUSION: AC is affected by liver fibrosis (MR elastography value ≥6.7 kPa) only in patients without hepatic steatosis (MRI-derived PDFF <5.2%). These values should be interpreted with caution in patients with advanced liver fibrosis.

Diagnostic performance of shear wave measurement in the detection of hepatic fibrosis: A multicenter prospective study.

AIM: This study aimed to establish the shear wave measurement (SWM) cut-off value for each fibrosis stage using magnetic resonance (MR) elastography values as a reference standard. METHODS: We prospectively analyzed 594 patients with chronic liver disease who underwent SWM and MR elastography. Correlation coefficients (were analyzed, and the diagnostic value was evaluated by the area under the receiver operating characteristic curve. Liver stiffness was categorized by MR elastography as F0 (<2.61 kPa), F1 (≥2.61 kPa, <2.97 kPa, any fibrosis), F2 (≥2.97 kPa, <3.62 kPa, significant fibrosis), F3 (≥3.62 kPa, <4.62 kPa, advanced fibrosis), or F4 (≥4.62 kPa, cirrhosis). RESULTS: The median SWM values increased significantly with increasing fibrosis stage (p < 0.001). The correlation coefficient between SWM and MR elastography values was 0.793 (95% confidence interval 0.761-0.821). The correlation coefficients between SWM and MR elastography values significantly decreased with increasing body mass index and skin-capsular distance; skin-capsular distance values were associated with significant differences in sensitivity, specificity, accuracy, or positive predictive value, whereas body mass index values were not. The best cut-off values for any fibrosis, significant fibrosis, advanced fibrosis, and cirrhosis were 6.18, 7.09, 8.05, and 10.89 kPa, respectively. CONCLUSIONS: This multicenter study in a large number of patients established SWM cut-off values for different degrees of fibrosis in chronic liver diseases using MR elastography as a reference standard. It is expected that these cut-off values will be applied to liver diseases in the future.

Natural course of post-COVID symptoms in adults and children.

More than 200 million COVID-19 survivors have lasting symptoms after recovering, but the duration and related risk factors remain uncertain. This study focused on all 6551 patients diagnosed with COVID-19 at a medical institution in Hiroshima from March 2020 to July 2022. In November 2022, a questionnaire survey was conducted regarding post-COVID symptoms and their duration. The prevalence and duration of post-COVID symptoms were illustrated using the Kaplan-Meier method. Risk factors for symptoms lasting over 3 months and interfering with daily life were assessed via multivariate logistic regression. A total of 2421 survivors responded: 1391 adults, 1030 children, median age 34 years (IQR 9-55), 51·2% male, 36·7% hospitalized, median time from infection to the survey was 295 days (IQR 201-538). Upon their initial recovery, the prevalence of post-COVID symptoms was 78·4% in adults and 34·6% in children. Three months later, the rates were 47·6% and 10·8%. After over one year, they were 31·0% and 6·8%. Regarding symptoms interfere with daily life, 304 people (12.6%) experienced symptoms lasting for over three months, with independent risk factors including age, being female, diabetes mellitus, infection during the Delta period, and current smoking. There was no significant association between vaccination history and post-COVID symptoms.

Comparison of six hepatocellular carcinoma prediction models in Japanese patients after sustained virologic response undergoing rigorous surveillance for hepatocellular carcinoma.

BACKGROUND AND AIM: While several predictive models for the development of hepatocellular carcinoma (HCC) have been proposed, including those for patients with chronic hepatitis C virus (HCV) infection who have achieved sustained virologic response (SVR), the best model may differ between regions. We compared the ability of six reported models to stratify the risk of post-SVR HCC in Japan, where rigorous surveillance and early detection of HCC is common. METHODS: A total of 6048 patients with no history of HCC who achieved SVR by oral direct-acting antiviral drugs were enrolled in this nationwide study. Patients continued HCC surveillance every 6 months after SVR. The incidence of post-SVR HCC was compared between risk groups using the aMAP score, FIB-4 index, Tahata model, GAF4 criteria, GES score, and ADRES score. RESULTS: During the observation period with a median duration of 4.0 years after SVR, post-SVR HCC developed in 332 patients (5.5%). All six models performed significantly at stratifying the incidence of HCC. However, Harrell's C-index was below 0.8 for all models (range, 0.660-0.748), indicating insufficient stratification ability. CONCLUSION: Although all six proposed models demonstrated a good ability to predict the development of post-SVR HCC, their ability to stratify the risk of post-SVRHCC was unsatisfactory. Further studies are necessary to identify the best model for assessing the risk of post-SVR HCC in regions where early detection of HCC is common.

Actual state of the diurnal masseteric electromyogram: Differences between awareness and non-awareness of awake bruxism.

PURPOSE: This study aimed to elucidate the relationship between diurnal masseter muscle activity and awareness of diurnal awake bruxism (d-AB) by conducting a comparative analysis of electromyographic (EMG) data from individuals with and without awareness of diurnal awake bruxism (d-AB), utilizing EMG data gathered from multiple subjects. METHODS: Unilateral masseter electromyography (EMG) recordings were performed during the daytime using an ultraminiature wearable EMG device. A total of 119 participants (59 with awareness of diurnal tooth clenching [d-TC] and 60 without awareness of d-TC) were included. Waveforms longer than 0.25 s with the two amplitude conditions, exceeding twice the baseline and >5% of maximum voluntary clenching, were extracted. In addition, the number of bursts and episodes (groups of bursts), burst duration, and burst peak amplitude were calculated for each participant. RESULTS: There were no significant differences in the EMG parameters between the groups with and without awareness of d-TC. Additionally, the frequency distribution of the number of EMG waveforms exhibited wide ranges and substantial overlap between the two groups. CONCLUSIONS: The variability in the number of bursts and episodes, burst peak amplitude, and burst duration among subjects suggests the need for an objective classification of d-AB severity based on EMG values. The absence of significant differences and large overlap in frequency distributions between the groups with and without awareness of d-TC indicate difficulty in predicting muscle activity solely based on awareness of d-AB.

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children.

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-α2 in 10 patients: IFN-α2 only in three, IFN-α2 plus IFN-ω in five, and IFN-α2, IFN-ω plus IFN-ß in two; IFN-ω only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-α2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-ω in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-α2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-ω only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-ω and/or IFN-α2.

A comparative study of hepatic steatosis using two different qualitative ultrasound techniques measured based on magnetic resonance imaging-derived proton density fat fraction.

AIM: This study aimed to evaluate the diagnostic performance of attenuation measurement (ATT; dual-frequency method) and improved algorithm of ATT (iATT; reference method) for the assessment of hepatic steatosis using magnetic resonance imaging (MRI)-derived proton density fat fraction (PDFF) as the reference standard. METHODS: We prospectively analyzed 427 patients with chronic liver disease who underwent ATT, iATT, or MRI-derived PDFF. Correlation coefficients were analyzed, and diagnostic values were evaluated by area under the receiver operating characteristic curve (AUROC). The steatosis grade was categorized as S0 (<5.2%), S1 (≥5.2%, <11.3%), S2 (≥11.3%, <17.1%), and S3 (≥17.1%) according to MRI-derived PDFF values. RESULTS: The median ATT and iATT values were 0.61 dB/cm/MHz (interquartile range 0.55-0.67 dB/cm/MHz) and 0.66 dB/cm/MHz (interquartile range 0.57-0.77 dB/cm/MHz). ATT and iATT values increased significantly as the steatosis grade increased in the order S0, S1, S2, and S3 (p < 0.001). The correlation coefficients between ATT or iATT values and MRI-derived PDFF values were 0.533 (95% confidence interval [CI] 0.477-0.610) and 0.803 (95% CI 0.766-0.834), with a significant difference between them (p < 0.001). For the detection of hepatic steatosis of ≥S1, ≥S2, and ≥S3, iATT yielded AUROCs of 0.926 (95% CI 0.901-0.951), 0.913 (95% CI 0.885-0.941), and 0.902 (95% CI 0.869-0.935), with significantly higher AUROC values than for ATT (p < 0.001, p < 0.001, p = 0.001). CONCLUSION: iATT showed excellent diagnostic performance for hepatic steatosis, and was strongly correlated with MRI-derived PDFF, with AUROCs of ≥0.900.

Early-Stage Chronic Kidney Disease and Related Health Care Spending.

Importance: The global burden of chronic kidney disease (CKD) is substantial and potentially leads to higher health care resource use. Objective: To examine the association between early-stage CKD and health care spending and its changes over time in the general population. Design, Setting, and Participants: Cohort study using nationwide health checkup and medical claims data in Japan. Participants included individuals aged 30 to 70 years with estimated glomerular filtration rates (eGFR) of 30 mL/min/1.73 m2 or greater at the baseline screening in 2014. Data analyses were conducted from April 2021 to October 2023. Exposure: The CKD stages at baseline, defined by the eGFR and proteinuria, were as follows: eGFR of 60 mL/min/1.73 m2 or greater without proteinuria, eGFR of 60 mL/min/1.73 m2 or greater with proteinuria, eGFR of 30 to 59 mL/min/1.73 m2 without proteinuria, and eGFR of 30 to 59 mL/min/1.73 m2 with proteinuria. Main Outcome and Measures: The primary outcome was excess health care spending, defined as the absolute difference in health care spending according to the baseline CKD stages (reference group: eGFR ≥60 mL/min/1.73 m2 without proteinuria) in the baseline year (2014) and in the following 5 years (2015 to 2019). Results: Of the 79 988 participants who underwent a health checkup (mean [SD] age, 47.0 [9.4] years; 22 027 [27.5%] female), 2899 (3.6%) had an eGFR of 60 mL/min/1.73 m2 or greater with proteinuria, 1116 (1.4%) had an eGFR of 30 to 59 mL/min/1.73 m2 without proteinuria, and 253 (0.3%) had an eGFR of 30 to 59 mL/min/1.73 m2 with proteinuria. At baseline, the presence of proteinuria and an eGFR less than 60 mL/min/1.73 m2 were associated with greater excess health care spending (adjusted difference, $178; 99% CI, $6-$350 for proteinuria; $608; 99% CI, $233-$983 for an eGFR of 30-59 mL/min/1.73 m2; and $1254; 99% CI, $134-$2373 for their combination). The study consistently found excess health care spending over the following 5 examined years. Conclusions and Relevance: In this cohort study of nationwide health checkup and medical claims data in Japan, early-stage CKD was associated with excess health care spending over the 5 examined years, and the association was more pronounced with a more advanced disease stage.

Incidence and Prevalence of Epilepsy in Japan: A Retrospective Analysis of Insurance Claims Data of 9,864,278 Insured Persons.

INTRODUCTION: The burden of epilepsy is thought to be high but is difficult to measure. Very few studies in Japan have attempted to estimate prevalence and incidence rates of epilepsy in Japan. METHODS: This retrospective cohort study used commercially collected nationwide insurance claims data from a cohort of 10 million persons between 2012 and 2019 among those aged 0 to 74 years. Using the claims data, cases were identified, and incidence and prevalence rates were estimated. RESULTS: A total of 9,864,278 persons were included. The average age was 34.5 (standard deviation, 18.5) years. A total of 77,312 persons were diagnosed with epilepsy over the 8-year observation period, with a prevalence rate of 6.0 per 1,000 persons with almost no difference by gender. The highest rates were seen among those aged 70-74 years; prevalence rates tended to rise with calendar year (5.4/1,000 in 2012 and 6.0/1,000 in 2019). The incidence rate of epilepsy was 72.1 per 100,000 person-years with slightly higher rates seen among females. Incidence rates were highest at ages less than 12 months (199.8/100,000 person-years), followed by the eldest age group (70-74 years, 179.4/100,000 person-years). CONCLUSION: Understanding the magnitude of disease burden is the basis of determining health policies. In this study, the prevalence and incidence of epilepsy in Japan was shown based on the analysis results of a large-scale general population insurance claims data covering all over Japan.