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.

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.

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.

Prevalence of Helicobacter pylori infection in the general population evaluated by a resident-register-based epidemiological study.

BACKGROUND: The current status of Helicobacter pylori infection in Japan has not been investigated. We evaluated the status of H. pylori infection in a Japanese general population using large-scale resident-register-based sampling. METHODS: All 6069 adults in a rural town and 6000 adults in two urban cities (3000 each), selected by register-based random sampling, were enrolled in our health check-up program. Antibody titers against Helicobacter pylori (cut-off value was 3 U/mL by Eiken E-plate) were evaluated, and subjects with a positive result were encouraged to undergo further examinations. RESULTS: A total of 1586 subjects participated in serum sampling. The overall prevalence of H. pylori infection was 40.0% (634/1586), and it increased with age both in rural and urban areas. Although the overall positive rate was higher in the rural area (49.4%) than in the urban areas (35.6 and 32.3%), there was no difference in H. pylori status of younger subjects between the two areas. Among 634 patients with a positive titer, 374 (59.0%) underwent further examinations including endoscopic examination, and 180/634 (28.4%) patients received eradication therapy. Gastric neoplasms (three adenocarcinomas and one adenoma) were found in our screening program. CONCLUSION: We clarified population-based random sampling data of H. pylori infection in a Japanese general population. In younger subjects, a decrease in the prevalence of H. pylori infection was confirmed both in rural and urban areas. This provides basic information for establishing a strategy to reduce gastric cancer deaths.

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.

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.

Mass Screening of SARS-CoV-2 Variants using Sanger Sequencing Strategy in Hiroshima, Japan.

This study aimed to develop the feasible and effective universal screening strategy of the notable SARS-CoV-2 variants by Sanger Sequencing Strategy and then practically applied it for mass screening in Hiroshima, Japan. A total of 734 samples from COVID-19 confirmed cases in Hiroshima were screened for the notable SARS-CoV-2 variants (B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.1, C.37, B.1.1.529, etc.). The targeted spike region is amplified by nested RT-PCR using in-house designed primer set hCoV-Spike-A and standard amplification protocol. Additionally, randomly selected 96 samples were also amplified using primer sets hCoV-Spike-B and hCoV-Spike-C. The negative amplified samples were repeated for second attempt of amplification by volume-up protocol. Thereafter, the amplified products were assigned for Sanger sequencing using corresponding primers. The positive amplification rate of primer set hCoV-Spike-A, hCoV-Spike-B and hCoV-Spike-C were 87.3%, 83.3% and 93.8% respectively for standard protocol and increased to 99.6%, 95.8% and 96.9% after second attempt by volume-up protocol. The readiness of genome sequences was 96.9%, 100% and 100% respectively. Among 48 mutant isolates, 26 were B.1.1.7 (Alpha), 7 were E484K single mutation and the rest were other types of mutation. Moreover, 5 cluster cases with single mutation at N501S were firstly reported in Hiroshima. This study indicates the reliability and effectiveness of Sanger sequencing to screen large number of samples for the notable SARS-CoV-2 variants. Compared to the Next Generation Sequencing (NGS), our method introduces the feasible, universally applicable, and practically useful tool for identification of the emerging variants with less expensive and time consuming especially in those countries where the NGS is not practically available. Our method allows not only to identify the pre-existing variants but also to examine other rare type of mutation or newly emerged variants and is crucial for prevention and control of pandemic.

Impact of robot-assisted surgery appearance on reduction of annual blood transfusion cases in Japan: application of meta-analysis and NDB open data.

In Japan, the robot-assisted partial nephrectomy (RAPN) started to be covered by health insurance since 2016, and it is replacing conventional open partial nephrectomy (OPN). RAPN is a minimally invasive surgery, and the spreading of RAPN in partial nephrectomy (PN) performed annually is expected to reduce the number of blood transfusions in Japan. The number of PN surgery in Japan was calculated using the Japanese NDB open data in 2018. We extracted articles comparing the transfusion rates of RAPN and OPN from 2017 to 2021 using PubMed, Web of Science, and Ichu-shi, and integrated the ratios of transfusion rates by meta-analysis. We estimated the reduction in the annual transfusion cases in PN due to the widespread use of RAPN. The total number of renal cancer surgeries in 2018 was 21,298, of which 3,876 (18.2%) were RAPN and 4,384 (20.6%) were OPN. For the comparison of transfusion implementation rate between RAPN and OPN, 871 articles were screened and 27 articles were included. The pooled ratio in transfusion rate of RAPN compared with OPN was 0.49 [0.46, 0.52]; the introduction of RAPN was estimated to have reduced the annual number of transfusions in PN by 9.1% compared with that of unintroduced RAPN. This study showed quantitatively evaluated the impact of the introduction of RAPN on the decrease in the annual number of transfusions in Japan. This method has the potential to evaluate the impact of robot-assisted surgery on the use of blood products for transfusion.

Screening for M-proteinemia consisting of monoclonal gammopathy of undetermined significance and multiple myeloma for 30 years among atomic bomb survivors in Hiroshima.

Monoclonal gammopathy (M-proteinemia) is a premalignant plasma cell disorder. The prevalence of M-proteinemia increases with age and is affected by genetic or environmental factors. Atomic bomb (A-bomb) survivors in Hiroshima are in an age range when they are susceptible to M-proteinemia. The prevalence and incidence of M-proteinemia in Hiroshima A-bomb survivors were investigated for 30 years (1989-2018) to examine the influence of radiation exposure. The overall prevalence of M-proteinemia among 38,602 A-bomb survivors was 2.4%. M-proteinemia prevalence at age 70 years and monoclonal gammopathy of undetermined significance (MGUS) incidence were not associated with radiation exposure category. Males had a 2.30-fold higher prevalence and a 2.08-fold higher incidence than females. The risk of incidence for MGUS was 4.32-fold higher in persons aged < 10 years at the time of the A-bombing and 2.56-fold higher in those aged 10-19 years compared with those aged over 30 years. IgG type M-proteinemia was common and the IgM type developed 5-8 years later than other immunoglobulin types. Exposure to radiation was not clearly associated with the prevalence of M-proteinemia or incidence of MGUS in Hiroshima A-bomb survivors. However, males and those aged < 20 years at A-bombing had higher susceptibility to MGUS.

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.

Lapatinib decreases the ACTH production and proliferation of corticotroph tumor cells.

Cushing's disease is almost always caused by hypersecretion of adrenocorticotropic hormone (ACTH) from a pituitary adenoma. A mutation in the deubiquitinase gene USP8 has been found in human ACTH-producing pituitary adenoma cells. This mutational hotspot hyperactivates USP8, rescuing epidermal growth factor receptor (EGFR) from lysosomal degradation and ensuring its sustained signaling in Cushing's disease. An EGFR inhibitor would be an effective anti-tumor agent in EGFR-related tumors. We investigated the effect of a potent dual tyrosine kinase inhibitor, lapatinib, on ACTH production and cell proliferation in AtT-20 mouse corticotroph tumor cells. Lapatinib decreased proopiomelanocortin (Pomc) mRNA levels and ACTH levels in AtT-20 cells and also inhibited cell proliferation, induced apoptosis, and decreased pituitary tumor-transforming gene 1 (Pttg1), a hallmark of pituitary tumors, mRNA levels. KSN/Slc nude mice were subcutaneously inoculated with AtT-20 cells. After 1 week, the mice were randomized either to control or lapatinib groups. The inhibitor decreased the tumor weight of AtT-20 allografts in vivo versus control mice. Lapatinib also significantly decreased Pomc and Pttg1 mRNA levels in the tumor and plasma ACTH and corticosterone levels in vivo. Thus, lapatinib decreases the ACTH production and proliferation of corticotroph tumor cells. An EGFR-targeting therapy could be an important treatment for Cushing's disease.

Evaluation of growth hormone-releasing peptide-2 for diagnosis of thyrotropin-producing pituitary adenomas.

Thyrotropin (TSH)-producing adenomas are a rare cause of hyperthyroidism and are a type of functional pituitary adenoma. The diagnosis of TSH-producing adenoma is a challenging problem in clinical endocrinology. Since growth hormone-releasing peptide-2 (GHRP-2) fails to induce TSH secretion in normal subjects, the effect of GHRP-2 on TSH levels was therefore examined in patients with TSH-producing adenomas. A total of 5 patients (4 women and 1 man) referred to our departments for further evaluation of pituitary hormones were followed-up using the GHRP-2, TSH-releasing hormone (TRH), octreotide, and bromocriptine tests to examine and evaluate TSH secretory dynamics in TSH-producing adenomas. Of 5 patients, 2 (40%) showed such a significant response, defined as a >50% increase in serum TSH level above baseline in the GHRP-2 test. Additionally, 1 patient showed a 48% increase in serum TSH level. In 1 patient whose adenoma was completely removed, basal serum concentrations of TSH were sufficiently suppressed after the operation, and serum TSH levels failed to increase in response to GHRP-2 administration. In 4 patients (80%), a poor response of serum TSH levels was observed in the TRH test. In 2 out of 5 patients (40%), serum TSH levels were significantly decreased following octreotide administration. No patient demonstrated a significant response to the bromocriptine test. In addition to TRH test, the GHRP-2 test as a potential diagnostic tool for TSH-producing pituitary adenomas.

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.

High prevalence of hepatitis B infections in Burkina Faso (1996-2017): a systematic review with meta-analysis of epidemiological studies.

BACKGROUND: Hepatitis B virus (HBV) infection was long considered an important public health concern in Burkina Faso and still represents a major cause of liver cancer and cirrhosis in the active population. To counter the problem, a national strategic plan was developed and adopted in July 2017 to coordinate viral hepatitis elimination's efforts. However evidence to support its implementation remains scanty and scattered. The main purpose of this study was to summarize available information from per-reviewed articles published over the last two decades to accurately estimate the prevalence of HBV infection in Burkina Faso. METHODS: We conducted a systematic search with meta-analysis of scientific articles using Science-Direct, Web-of-Science, PubMed/Medline, and Google Scholar. We systematically assessed all relevant publications that measured the prevalence of hepatitis B surface antigen and which were published between 1996 and 2017. We estimated the national HBV prevalence and its 95% confident interval. We subsequently adjusted the meta-analysis to possible sources of heterogeneity. RESULTS: We retrieved and analyzed a total of 22 full text papers including 99,672 participants. The overall prevalence was 11.21%. The prevalence after adjustment were 9.41%, 11.11%, 11.73% and 12.61% in the general population, pregnant women, blood donors and HIV-positive persons respectively. The prevalence was higher before implementation of HBV universal vaccination and decreased from 12.80% between 1996 and 2001 to 11.11% between 2012 and 2017. The prevalence was also higher in rural area 17.35% than urban area 11.11%. The western regions were more affected with 12.69% than the central regions 10.57%. The prevalence was 14.66% in the boucle of Mouhoun region and 14.59 in the center-west region. Aggregate data were not available for the other regions. CONCLUSIONS: HBV has clearly an important burden in Burkina Faso as described by its high prevalence and this problem significantly challenges the national health care system. There is an urgent need for effective public health interventions to eliminate the problem. However, higher quality data are needed to produce reliable epidemiological estimates that will guide control efforts towards the achievement of the national strategic plan's goals.

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.

Incidence and risk factors of colorectal cancer based on 56 324 health checkups: A 7-year retrospective cohort study.

BACKGROUND AND AIM: Although mortality rates of colorectal cancer (CRC) have been increasing in Japan, its screening rates remain stagnant at 19.2% among Japanese population aged > 40 years in 2014. To evaluate the importance of CRC screening by fecal occult blood test (FOBT), this study estimated the incidence of FOBT-positivity and CRC by sex-age stratification and clarified the risk factors for CRC. METHODS: Between 2007 and 2014, 56 324 residents (21 517 men and 34 807 women) were enrolled in this study. The sex-age-stratified incidence rates of FOBT-positivity and CRC were estimated by records from health checkups and colonoscopy. Regarding CRC incidence rate in particular, positive predictive value was adopted to adjust bias of FOBT-positivity that did not undergo colonoscopy by person-year method. To investigate the risks of CRC onset, a nested case-control study with 1:10 person-matching on sex and age was performed. RESULTS: Incidence rates of FOBT-positivity and CRC are 4183/100 000 person-year (100 Kpy) and 141.3/100 Kpy, respectively. In both cases, men has higher incidence rate than women (1.3 times for FOBT; 4977 vs 3718/100 Kpy and 2.3 times for CRC; 217.0 vs 96.4/100 Kpy). CONCLUSIONS: The records from health checkups were useful to estimate incidence rates of CRC with this procedure. The age-stratified incidence rate indicated the importance of CRC screening by FOBT, especially for men and those aged > 50 years. Additionally, it is strongly recommended to do further investigation if positive for initial FOBT screening especially for those who are > 70 years.

A Case of Hyperparathyroidism due to a Large Intrathyroid Parathyroid Adenoma with Recurrent Episodes of Acute Pancreatitis.

We report a case of a 66-year-old woman who developed hyperparathyroidism due to a large intrathyroid parathyroid adenoma with episodes of acute pancreatitis. She had previously been treated for acute pancreatitis twice. Serum calcium was 12.4 mg/dL, and intact parathyroid hormone was 253 pg/dL. Ultrasonography and computed tomography of the neck with contrast enhancement revealed a soft tissue mass (28 mm transverse diameter) within the left lobe of the thyroid. 99mTc-MIBI scintigraphy demonstrated focal accumulation due to increased radiotracer uptake in the left thyroid lobe. Left hemithyroidectomy was performed. Histopathology showed no signs of invasion, and this is consistent with parathyroid adenoma. Immunostaining was positive for expression of chromogranin A and parathyroid hormone. The patient had no episode of pancreatitis after the operation. In a patient with recurrent episodes of pancreatitis, the possibility of complication with hyperparathyroidism should be considered.

Evaluation of the (1-24) adrenocorticotropin stimulation test for the diagnosis of primary aldosteronism.

OBJECTIVE: The purpose of this study was to investigate the diagnostic power of the adrenocorticotropin (ACTH) stimulation test in patients with primary aldosteronism (PA) and those with aldosterone-producing adenoma (APA). DESIGN: This study was based on a retrospective database analysis. SUBJECTS AND METHODS: We assessed 158 hypertensive patients with a high plasma aldosterone-to-renin ratio (ARR) including 97 with at least one positive confirmatory test result who did not undergo surgery and comprised a "possible PA" group, 19 with negative results in all tests who were the "non-PA" group, and 41 diagnosed with APA following surgery who were the APA group. The "confirmed PA group" included APA patients and patients from the possible PA group showing both high ARR and hypokalemia. One case was diagnosed as a metastasis. RESULTS: Receiver-operating characteristic (ROC) analysis showed that the diagnostic accuracy of ACTH test was not very effective in differentiating between APA patients and possible PA and non-PA patients. The optimal cut-off value of maximal plasma aldosterone concentration for differentiating between patient in the confirmed PA group and other patients showed moderate accuracy. CONCLUSIONS: The ACTH test may not be useful as a screening or confirmatory test, but the test may be useful for differentiating between patients with confirmed PA and the rest of the cohort. The positive finding of the ACTH test may at least support a higher likelihood of lateralizing on adrenal venous sampling.

[Epidemiology of Hepatitis Virus Infection and Its Control from the Epidemiological Point of View.]

In Japan, hepatitis and liver cancer measures, based on the hepatitis Basic Measures Law, have been pro- moted for 25 years with a focus on advancing the diagnosis, treatment, and inspection. In 2011, the estimated number of people persistently infected with the hepatitis virus in Japan was esti- mated to be about 2.1-2.8 per million people. In addition, "persistent infections latent in society of people unaware of their infection" has been estimated to involve 777,000 people. Since it is now a time of introducing new drugs for effective anti-viral therapy, in order to continue to more effectively implement the hepatitis and liver cancer measures, regional cooperation, such as the construction of a liver disease patient follow-up system, is important.