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.

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.

Variant-specific symptoms after COVID-19: a hospital-based study in Hiroshima.

BackgroundSymptoms after COVID-19 recovery by SARS-CoV-2 strains are unspecified.MethodsThis self-administered questionnaire-based study was conducted to investigate symptoms after COVID-19 recovery at one of the main hospitals for COVID-19 treatment in Hiroshima, Japan, from September 2020 to March 2022 for patients who visited follow-up consultations after COVID-19. Study subjects were divided into four groups (Wild-type, Alpha, Delta, and Omicron periods) according to COVID-19 onset date. Hierarchical cluster analysis was performed to determine symptom clusters and investigate risk factors for each symptom cluster using multivariate analysis.ResultsAmong 385 patients who enrolled in this study, 249 patients had any persistent symptoms at a median of 23.5 [IQR, 20-31] days after COVID-19 onset. Among patients with any persistent symptoms, symptom clusters including olfactory or taste disorders, respiratory symptoms, and cardiac symptoms were found. Respiratory symptoms were more frequent among patients infected in the Omicron period compared to the Wild-type period (AOR, 3.13; 95% CI, 1.31-7.48; p=0.0101). Compared to patients who recovered from mild COVID-19, patients who needed for oxygen or ventilation support suffered fewer post-COVID-19 respiratory symptoms (AOR, 0.46; 95% CI, 0.22-0.97; p=0.0415) but more post-COID-19 cardiac symptoms among them (AOR, 2.67; 95% CI, 1.26-5.65; p=0.0103). Olfactory or taste disorders were fewer among patients infected in the Omicron period compared to the Wild-type period (AOR, 0.14; 95% CI, 0.04-0.46; p=0.0011).ConclusionThis study revealed that symptoms after COVID-19 may vary depending on the infected strain.

Distribution of FIB-4 index in the general population: analysis of 75,666 residents who underwent health checkups.

BACKGROUND: Fatty liver is frequently found in a general population, and it is critical to detect advanced fibrosis. FIB-4 index is considered a useful marker for evaluating liver fibrosis but the distribution of FIB-4 index in the general population remains unknown. METHODS: This cross-sectional study included residents who underwent ultrasonography at health checkups in Hiroshima or Iwate prefectures. The distribution of FIB-4 index in the total study population (N = 75,666) as well as in non-alcoholic fatty liver disease (NAFLD) populations (N = 17,968) and non-drinkers without fatty liver populations (N = 47,222) was evaluated. The distribution of aspartate aminotransferase (AST) levels, alanine aminotransferase (ALT) levels was also evaluated. RESULTS: The mean FIB-4 index in the total study population was 1.20 ± 0.63. FIB-4 index ≥ 2.67, which indicates a high risk of liver fibrosis, was found in 16.4% of those aged ≥ 70 years. In the NAFLD population, 58.1% of those in their 60 s and 88.1% of those ≥ 70 years met the criteria for referral to hepatologists by using the recommended FIB-4 index cutoff value (≥ 1.3). The mean FIB-4 index in the NAFLD population (1.12 ± 0.58) was significantly lower than in the non-drinkers without fatty liver (1.23 ± 0.63, p < 0.0001). The non-drinkers without fatty liver tended to have higher AST relative to ALT levels (60.0% with AST/ALT > 1.0), whereas the results in the NAFLD population were opposite (14.8% with AST/ALT > 1.0). AST > ALT resulted in a higher FIB-4 index in non-drinkers without fatty liver due to the nature of FIB-4 index formula. CONCLUSIONS: The cutoff value of FIB-4 index (≥ 1.3) for triaging the elderly people with fatty liver for referral to hepatologists should be reconsidered to avoid over-referral. Due to the impact of age and characteristics of AST/ALT ratios, there is no prospect of using FIB-4 index for primary screening for liver fibrosis in a general population of unknown presence or absence of liver disease, even though it can be easily calculated using routine clinical indices. It is desired to develop a non-invasive method for picking up cases with advanced fibrosis latent in the general population.

Impact of antiviral therapy for disease progression and non-invasive liver fibrosis index in patients with chronic hepatitis C: Markov chain model analysis.

BACKGROUND/AIM: Antiviral therapy advancements resulted in an era in which eradication of hepatitis C has become a goal, however, there are few reports on the long-term course of liver disease progression with antiviral therapy. The aim of this study was to use the Markov model to analyze disease progression and non-invasive liver fibrosis index in hepatitis C Patients. METHODS: Patients with chronic hepatitis C (n = 1432) were diagnosed between January 2012 and May 2021 in the Musashino Red Cross Hospital. Patients with other hepatitis virus co-infection, chronic liver disease, and hepatocellular carcinoma (HCC) at the beginning of the study were excluded. A total of 618 patients with a 1-year or longer observation period were studied. The liver disease state was defined as chronic hepatitis (CH), compensated liver cirrhosis (CLC), decompensated liver cirrhosis (DLC), and HCC. RESULTS: Cirrhosis and high FIB-4 index (≥3.61) were 42 cases (6.8%) and 208 cases (33.6%), respectively at the start of the study. The 40 years estimated transition analysis of 40-year-old CH low FIB-4 level (<3.61) revealed that the proportion of CH low/high, CLC low/high, DLC low/high, and HCC were 10.83%/10.86%, 0.35%/2.64%, 0%/3.21% 72.11% in untreated unit and 47.83%/9.21%, 6.69%/1.32%, 0.70%/0.99%, 33.27% in treated unit, respectively. Antiviral therapy suppressed liver fibrosis, disease progression, and HCC development significantly. CONCLUSION: Markov model analysis of hepatitis C virus patients showed the impact of antiviral therapy on the suppression of disease progression in the order of CH, CLC, and DLC.

Adverse reactions to the BNT162b2 and mRNA-1273 mRNA COVID-19 vaccines in Japan.

INTRODUCTION: The BNT162b2 and mRNA-1273 COVID-19 vaccines are the main vaccines that have been used for mass vaccination in Japan. Information on adverse reactions to COVID-19 vaccines in the Japanese population is limited. METHODS: We conducted an online survey on self-reported adverse reactions in individuals who had received two doses of the BNT162b2 or mRNA-1273 vaccine. The incidence of adverse events after each dose of vaccine was investigated. Propensity score matching was used to compare the incidence of adverse reactions after the second dose of the BNT162b2 and mRNA-1273 vaccines. RESULTS: After the first and second doses of the BNT162b2 vaccine, and the first and second doses of the mRNA-1273 vaccine, 890, 853, 6401, and 3965 individuals, respectively, provided complete responses. Systemic reactions, including fever, fatigue, headache, muscle/joint pain, and nausea were significantly more common in females, individuals aged <50 years, and after the second dose. The incidence of injection site pain did not differ significantly according to the dose. The incidence of delayed injection site reactions after the first dose of mRNA-1273 vaccine was 3.9% and 0.8% among females and males, respectively, and 10.6% among females aged 40-69 years. Local and systemic reactions after the second dose, including fever, fatigue, headache, muscle/joint pain, nausea, and skin rash were more common in individuals who had received the mRNA-1273 vaccine. CONCLUSIONS: Adverse reactions were more frequently reported in females, younger individuals, and after the mRNA-1273 vaccine.

Comparison of liver disease state progression in patients with eradication of versus persistent infection with hepatitis C virus: Markov chain analysis.

To investigate the long-term prognosis of liver disease in patients with hepatitis C virus (HCV) eradication after antiviral therapy versus those with persistent HCV infection. Four hundred and eighty patients (5259 person-years [PYs]) who received interferon-based therapy and achieved sustained virologic response and 848 patients (3853 PYs) with persistent HCV infection were included. In the analysis of 1-year liver disease state transition probability matrices using Markov chain models, progression to cirrhosis from the chronic hepatitis state was observed (0.00%-0.63%) in patients with HCV eradication. Among patients with chronic hepatitis or cirrhosis and HCV eradication, hepatocellular carcinoma (HCC) development was observed in males aged ≥ 50 years (0.97%-1.96%) and females aged ≥ 60 years (0.26%-5.00%). Additionally, in patients with cirrhosis and HCV eradication, improvement to chronic hepatitis was also observed (4.94%-10.64%). Conversely, in patients with chronic hepatitis and persistent HCV infection, progression to cirrhosis was observed in males aged ≥ 30 years and female aged ≥ 40 years (0.44%-1.99%). In males aged ≥ 40 years and female aged ≥ 50 years with cirrhosis, the transition probability for HCC was relatively high (4.17%-14.02%). Under the assumption of either chronic hepatitis or cirrhosis at age 40 or 60 years as the starting condition for simulation over the next 30 or 40 years, respectively, the probability of HCC was higher in patients with persistent HCV infection than those with HCV eradication. In conclusion, HCV eradication can reduce the risk of developing cirrhosis or HCC in patients with chronic HCV infection.

Relationship between drinking frequency and fatty liver prevalence or incidence in Japanese undergoing health checkup in 2008-2019.

BACKGROUND & AIMS: The relationship between the frequency of drinking and fatty liver in the general population is still poorly understood. This study analysed data from a large cohort who underwent health checkups in Japan between 2008 and 2019 to investigate the prevalence and incidence of fatty liver by alcohol consumption and risk factors for fatty liver. METHODS: The prevalence of fatty liver diagnosed with ultrasonography was calculated in 75,670 residents. The incidence of fatty liver in 31,062 residents who underwent ultrasonography at least twice during the period without fatty liver at the first time was calculated using the person-year method. Multivariate logistic analysis was performed to investigate risk factors associated with the prevalence and incidence of fatty liver. RESULTS: The prevalence of fatty liver was 27.6% (95% confidence interval [CI], 27.2-27.9) in non-drinkers, 28.5% (27.5-29.5) in moderate-drinkers and 28.0% (26.0-29.9) in heavy-drinkers. The incidence of fatty liver was 3,084/100,000 person-years (2,997-3,172/100,000) in non-drinkers, 3,754/100,000 person-years (3,481-4,042/100,000) in moderate-drinkers and 3,861/100,000 person-years (3,295-4,497/100,000) in heavy-drinkers. The prevalence and incidence of fatty liver were not associated with drinking status. Obesity was the most important independent risk factor (prevalence: adjusted odds ratio [AOR], 6.3; 95% CI, 6.0-6.5; incidence: AOR, 2.4; 95% CI, 2.3-2.6). CONCLUSIONS: Drinking status does not affect the prevalence or incidence of fatty liver in Japanese residents undergoing health checkups. From a public health perspective, measures for obesity control must be prioritised to reduce the burden of disease of fatty liver in Japan.

Long-term prognosis of liver disease in patients with eradicated chronic hepatitis C virus: An analysis using a Markov chain model.

AIM: The long-term prognosis of patients with chronic hepatitis C virus (HCV) infection who have received antiviral therapy and who demonstrate HCV eradication remains incompletely characterized. In this study, we investigated the long-term prognosis of liver disease in patients with eradication of HCV. METHODS: A total of 552 patients with chronic HCV infection (6815 person-years) who were treated with interferon-based therapy and who achieved sustained virologic response were included. Yearly transition probabilities for each liver state (chronic hepatitis, cirrhosis, and hepatocellular carcinoma [HCC]) were calculated using a Markov chain model. RESULTS: In the analysis of 1-year liver disease state transition probabilities, progression to cirrhosis occurred in 0.5-2.1% of male patients with chronic hepatitis across all age groups. In male patients with cirrhosis, HCC developed in 0.6-1.9% of patients over the age of 50 years. In female patients with chronic hepatitis, progression to cirrhosis occurred in 0.4-2.1% of patients across all age groups. In addition, in female patients with cirrhosis, HCC developed in those aged 60-69 (0.4%) and 70-79 (0.4%) years. Under the assumption of either a chronic hepatitis or cirrhosis state at age 40 or 60 years as the starting condition for simulation over the next 40 or 20 years, respectively, the probability of HCC gradually increased with age and was higher in male patients. CONCLUSIONS: The development or progression of cirrhosis and the development of HCC are risks in HCV patients despite HCV eradication, not only in those with cirrhosis but also in those with chronic hepatitis.

Natural history of liver-related disease in patients with chronic hepatitis C virus infection: An analysis using a Markov chain model.

BACKGROUND: Long-term prognosis of patients with chronic hepatitis C infection (HCV) remains incompletely characterized. We investigated the long-term prognosis of liver disease in patients with chronic HCV infection who have not received antiviral therapy. METHODS: A total of 2304 patients with chronic HCV who were not received interferon-based therapy were included. RESULTS: In the assessment of 1-year disease state of liver transition probabilities, progression to chronic hepatitis occurred in 12% to 14% of patients across all age groups in male asymptomatic carriers. In male patients with chronic hepatitis, progression to cirrhosis was observed mostly in the 60 to 69 (7.6%) and ≥70 age groups (9.6%). In addition, in male patients with cirrhosis, HCC development occurred in approximately 5% of patients over the age of 40. In female asymptomatic carriers, progression to chronic hepatitis was observed in 6% to 14% of patients across all age groups. In female patients with chronic hepatitis, progression to cirrhosis was observed mostly in the 60 to 69 (8.7%) and ≥70 (7.4%) age groups. In addition, in female patients with cirrhosis, HCC development occurred in 0.9% to 3.3% of patients over the age of 50. Under assumptions of either chronic hepatitis or asymptomatic carrier state at age 40 as the starting condition for simulation over the following 40 years, the probability of HCC gradually increased with age and was higher in male patients. CONCLUSIONS: There is a risk of cirrhosis or HCC development in HCV patients with not only chronic hepatitis but the asymptomatic carrier state as well.

Natural course of persistent hepatitis B virus infection in hepatitis B e antigen-positive and hepatitis B e antigen-negative cohorts in Japan based on the Markov model.

This population-based study examined the natural course of hepatitis B e antigen (HBeAg)-positive or HBeAg-negative persistent hepatitis B virus (HBV) infection, adjusted by age and liver disease states using a Markov model. Using 12 417 person-years data (n = 862), annual transition probabilities were estimated, and age-adjusted cumulative incidence and natural history of persistent HBV infection were simulated in both sexes of groups 1 (HBeAg-negative status with HBV DNA level <4.0 log IU/mL at entry) and 2 (persistent HBeAg-positive status throughout the study). In group 1, 15.26% of 30-years old men with chronic hepatitis (CH) were expected to remain in the same state at age 65 years, 28.32% subsided into an hepatitis B surface antigen (HBsAg)-negative state, and 13.20% developed hepatocellular carcinoma (HCC). The expectations for 40-years old men in group 1 were 21.43%, 19.86%, and 15.04%, respectively. The expectations for 30 years women in group 1 were 30.57%, 21.15%, and 4.08%, respectively. These results suggest that HBeAg positivity caused a higher risk of HCC onset in persistent HBV infection after adjustments for age, sex, and liver disease state. HCC was likely to develop, but unlikely to subside into HBsAg clearance, remaining in a CH state with aging, regardless of HBeAg state. Furthermore, both HCC development and HBsAg clearance occurred more frequently in men than in women, irrespective of HBeAg status.

Incidence rates of hepatitis C virus infection among blood donors in Japan: a nationwide retrospective cohort study.

BACKGROUND: The classification of many new cases of hepatitis virus infection as overt hepatitis does not reflect the true incidence of infection because the disease takes an asymptomatic course in some cases. In this retrospective cohort study, we aimed to estimate the incidence rates of new hepatitis C virus (HCV) infections among the blood donors. STUDY DESIGN AND METHOD: A 5-year retrospective cohort study was conducted to estimate the incidence rates by using the medical records of the blood donors between 2008 and 2013 for HCV infection. HCV seroconversions were investigated using a chemiluminescent enzyme immunoassay and then confirmed by nucleic acid amplification tests. RESULTS: The incidence rate of HCV infection was 0.40 per 100,000 person-years (95% confidence interval, 0.27-0.57) for HCV RNA seroconversion only and 7.32 per 100,000 person-years (95% confidence interval, 6.73-7.95) if either HCV RNA or anti-HCV seroconversion were taken into consideration. No significant difference of new HCV infections was found between the sexes. CONCLUSION: The incidence rate of HCV infection of this study was lower than that detected in a previous 1994-2004 study in which HCV incidence was 1.86 per 100,000 person-year, which reflects the presence of an effective blood screening system and health strategies targeting hepatitis control and prevention.

Cost-effectiveness analyses of anti-hepatitis C virus treatments using quality of life scoring among patients with chronic liver disease in Hiroshima prefecture, Japan.

AIM: We estimated the cost-effectiveness of direct-acting antiviral treatment (DAA) compared to triple therapy (simeprevir, pegylated interferon-α [Peg-IFN], and ribavirin [RBV]) (scenario 1), Peg-IFN + RBV (scenario 2), and non-antiviral therapy (scenario 3). METHODS: Cost-effectiveness was evaluated as incremental cost-effectiveness ratios (ICERs) using direct costs and indirect costs, which included loss of wages during the patient's lifetime due to early death caused by viral hepatitis infection. Quality of life (QOL) scores were determined by EQ-5D-3L questionnaire survey on 200 HCV patients in Hiroshima. RESULTS: The QOL scores for chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma were estimated as 0.871, 0.774, and 0.780, respectively. The follow-up period that the ICER of scenario 1 becomes shortest (cost <¥6 million) was 25 years after treatment in men and women who started treatment at the age of 20-60. In contrast, those of scenarios 2 and 3 was 10 years after treatment in patients who started treatment at age <80 years. Based on the sensitivity analysis in scenario 1, the most significant factor affecting the value of ICER is the QOL score after sustained virologic response (SVR), followed by the SVR rate of DAA or follow-up period. CONCLUSIONS: Direct-acting antiviral treatment was estimated to be cost-effective from 10 to 25 years after treatment, depending on the SVR rate of the drugs and the age of onset of treatment. In order to increase the cost-effectiveness of DAA treatment, measures or effort to improve the QOL score of patients after SVR are necessary.

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.

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.

Burden of chronic hepatitis B and C infections in 2015 and future trends in Japan: A simulation study.

Background: Determining the number of chronic hepatitis B (HBV) and C virus (HCV) infections is essential to assess the progress towards the World Health Organization 2030 viral hepatitis elimination goals. Using data from the Japanese National Database (NDB), we calculated the number of chronic HBV and HCV infections in 2015 and predicted the trend until 2035. Methods: NDB and first-time blood donors data were used to calculate the number of chronic HBV and HCV infections in 2015. A Markov simulation was applied to predict chronic infections until 2035 using transition probabilities calculated from NDB data. Findings: The total number of chronic HBV and HCV infections in 2015 in Japan was 1,905,187-2,490,873 (HCV:877,841-1,302,179, HBV:1,027,346-1,188,694), of which 923,661-1,509,347 were undiagnosed or diagnosed but not linked to care ("not engaged in care"), and 981,526 were engaged in care. Chronic HBV and HCV infections are expected to be 923,313-1,304,598 in 2030, and 739,118-1,045,884 in 2035. Compared to 2015, by 2035, the number of persons with HCV not engaged in care will decline by 59·8 - 76·1% and 86·5% for patients in care. For HBV, a 47·3 - 49·3% decrease is expected for persons not engaged in care and a decline of 26·0% for patients engaged in care. Interpretation: Although the burden of HBV and HCV is expected to decrease by 2035, challenges in controlling hepatitis remain. Improved and innovative screening strategies with linkage to care for HCV cases, and a functional cure for HBV are needed. Funding: Japan Ministry of Health, Labour and Welfare.

Seroepidemiological study of factors affecting anti-spike IgG antibody titers after a two-dose mRNA COVID-19 vaccination in 3744 healthy Japanese volunteers.

Several factors related to anti-spike(S) IgG antibody titers after mRNA COVID-19 vaccination have been elucidated, but the magnitude of the effects of each factor has not been fully understood. This cross-sectional study assessed anti-S and anti-nucleocapsid (N) antibody titers on 3744 healthy volunteers (median age, 36 years; IQR, 24-49 years; females, 59.0%) who received two doses of mRNA-1273 or BNT162b2 vaccine and completed a survey questionnaire. Multiple regression was conducted to identify factors associated with antibody titers. All but one participant tested positive for anti-S antibodies (99.97%). The following factors were independently and significantly associated with high antibody titer: < 3 months from vaccination (ratio of means 4.41); mRNA-1273 vaccine (1.90, vs BNT162b2); anti-N antibody positivity (1.62); age (10's: 1.50, 20's: 1.37, 30's: 1.26, 40's: 1.16, 50's: 1.15, vs ≧60's); female (1.07); immunosuppressive therapy (0.54); current smoking (0.85); and current drinking (0.96). The largest impact on anti-S IgG antibody titers was found in elapsed time after vaccination, followed by vaccine brand, immunosuppressants, previous SARS-CoV-2 infection (anti-N antibody positive), and age. Although the influence of adverse reactions after the vaccine, gender, smoking, and drinking was relatively small, they were independently related factors.

The role of discrimination in the relation between COVID-19 sequelae, psychological distress, and work impairment in COVID-19 survivors.

Perceived discrimination and work impairment are commonly observed in COVID-19 survivors, but their relationship has not been well understood. We aimed to evaluate the role of discrimination in the development of psychological distress and work impairment in COVID-19 survivors. From April 2020 to November 2021, 309 patients were recruited at two designated COVID-19 hospitals in Japan. Participants completed a standardized questionnaire including COVID-19 sequelae, psychological distress, impairments in work performance and perceived discrimination. The majority of participants (62.5%) experienced one or more COVID-19 sequelae. Psychological distress was observed in 36.9% and work impairment in 37.9%. In multivariate logistic regression analyses, COVID-19 sequelae and discrimination were associated with both psychological distress and work impairment. Mediation analysis demonstrated that the direct effect of sequelae on work impairment was non-significant after accounting for psychological distress, suggesting that the effect of sequelae on work impairment was mainly mediated through psychological distress. These findings were replicated in a subgroup analysis limited to patients with mild COVID-19. We conclude that discrimination plays an important role in the development of psychological distress and work impairment, and that both discrimination and psychological distress should be targets of intervention in COVID-19 survivors.

PNPLA3 and HLA-DQB1 polymorphisms are associated with hepatocellular carcinoma after hepatitis C virus eradication.

BACKGROUND: Even though both interferon (IFN)-based and direct-acting antiviral (DAA) therapies against hepatitis C virus (HCV) reduce the risk of hepatocellular carcinoma (HCC), post-sustained virological response (SVR) patients remain at elevated risk of HCC. METHODS: A total of 4620 patients who achieved SVR were enrolled in this retrospective cohort study. After excluding patients who had a history of HCC or developed HCC within 1 year and whose follow-up period was less than 1 year and who were positive for HBsAg, we investigated the association between clinical characteristics and HCC development after SVR in the remaining 3771 patients. RESULTS: Median observation period was 41 months. We confirmed known risk factors. In addition, we found that PNPLA3 and HLA-DQB1 polymorphisms were associated with HCC after SVR. Finally, we propose an estimation model for the incidence of HCC after SVR. Based on gender, FIB-4 index, AFP, and PNPLA3 polymorphism, about 18% of all patients were classified as having high risk, with a cumulative incidence rate (CIR) at 5 years of 16.5%. Another 17% were classified as having moderate risk with a CIR of 7.6%. The remaining 65% showed a CIR of 0.5%. The effect of PNPLA3 polymorphism might be more pronounced in patients with lower body mass index (BMI) and without diabetes mellitus compared to those with higher BMI and diabetes mellitus. CONCLUSIONS: We demonstrated that PNPLA3 and HLA-DQB1 polymorphisms were associated with HCC after SVR. These findings might be useful to inform risk stratification for HCC surveillance after SVR.