Brachial-Ankle Pulse Wave Velocity is Associated with Incident Dementia in Patients with Cerebral Small-Vessel Disease.

AIMS: Increased arterial stiffness is associated with the severity of cerebral small-vessel disease (SVD) and may predict incident dementia. This study investigated the predictive value of brachial-ankle pulse wave velocity (ba-PWV) for dementia and cognitive decline. METHODS: Data were obtained from a Japanese cohort of 478 patients who underwent ba-PWV measurement. Magnetic resonance imaging (MRI) was used to evaluate SVD severity. The Mini-Mental State Examination (MMSE) and the Japanese version of the Montreal Cognitive Assessment (MoCA-J) were used to assess the cognitive function. The primary outcome was the incidence of dementia. The secondary outcome was cognitive change during three years of follow-up. RESULTS: The median age was 71 years old, 61% were men, and the median ba-PWV was 1787 cm/s. Dementia was diagnosed in 23 patients during a mean follow-up of 4.8 years. A Cox proportional hazard regression analysis revealed that the highest quartile (ba-PWV ≥ 2102 cm/s) was associated with a significantly higher risk of dementia than the first to third quartiles (ba-PWV ≤ 2099 cm/s) after adjusting for risk factors, the mean blood pressure, the MoCA-J score, and SVD severity (adjusted HR, 3.40; 95% CI, 1.24-9.34; P=0.018). Longitudinal cognitive changes in 192 patients indicated that ba-PWV was negatively related to changes in the MoCA-J score (r=-0.184, P=0.011). The decline in the MoCA-J score in the highest quartile was greater than that in the first to third quartiles after adjusting for risk factors, SVD severity, and baseline MoCA-J score (P=0.017). CONCLUSIONS: ba-PWV was associated with incident dementia and cognitive decline, independent of age, risk factors, the baseline cognitive function, and the SVD severity.

Small-Vessel Disease and Intracranial Large Artery Disease in Brain MRI Predict Dementia and Acute Coronary Syndrome, Respectively: A Prospective, Observational Study in the Population at High Vascular Risk.

BACKGROUND: We aimed to clarify the predictive value of cerebral small-vessel disease and intracranial large artery disease (LAD) observed in magnetic resonance imaging of the brain and magnetic resonance angiography on future vascular events and cognitive impairment. METHODS AND RESULTS: Data were derived from a Japanese cohort with evidence of cerebral vessel disease on magnetic resonance imaging. This study included 862 participants who underwent magnetic resonance angiography after excluding patients with a modified Rankin Scale score >1 and Mini-Mental State Examination score <24. We evaluated small-vessel disease such as white matter hyperintensities and lacunes in magnetic resonance imaging and LAD with magnetic resonance angiography. Outcomes were incident stroke, dementia, acute coronary syndrome, and all-cause death. Over a median follow-up period of 4.5 years, 54 incident stroke, 39 cases of dementia, and 27 cases of acute coronary syndrome were documented. Both small-vessel disease (white matter hyperintensities and lacunes) and LAD were associated with stroke; however, only white matter hyperintensities were related to dementia. In contrast, only LAD was associated with acute coronary syndrome. Among the 357 patients with no prior history of stroke, coronary or peripheral artery disease, or atrial fibrillation, white matter hyperintensities emerged as the sole predictor of future stroke and dementia, while LAD was the sole predictor of acute coronary syndrome. CONCLUSIONS: Among cerebral vessels, small-vessel disease could underlie the cognitive impairment while LAD was associated with coronary artery disease as atherosclerotic vessel disease.

Association of Age-Related Spontaneous Internal Jugular Vein Reflux with Cognitive Impairment and Incident Dementia.

BACKGROUND: It remains unclear whether changes in the venous circulation contribute to cognitive decline. OBJECTIVE: This study aimed to clarify whether the spontaneous jugular vein reflux (JVR) is associated with cognitive impairment and incident dementia. METHODS: Patients with any evidence of cerebral vessel disease on magnetic resonance imaging (MRI) were consecutively enrolled between October 2015 to July 2019. We employed carotid duplex sonography to measure the internal jugular vein (IJV). The subjects were classified into two groups based on the degree of JVR on either side: none, mild (JVR(-) group) and moderate, severe (JVR (+) group) JVR. They underwent both the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment-Japanese (MoCA-J) global tests. Their cognitive status was prospectively assessed until March 2023. RESULTS: 302 patients with an MMSE score ≥24 underwent duplex sonography of the IJV. Among them, 91 had spontaneous JVR on either side. Both MMSE and MoCA-J were significantly lower in patients with JVR (+) group than in the JVR (-) group. After the adjustment for risk factors and MRI findings, intergroup differences in MoCA-J remained significant. Among the cognitive subdomains, median executive function and memory scores were significantly lower in the JVR (+) group than in the JVR (-) group. During the median 5.2-year follow-up, 11 patients with incident dementia were diagnosed. Patients with severe JVR were significantly more likely to be diagnosed with dementia (log-rank test, p = 0.031). CONCLUSIONS: Spontaneous IJV reflux especially severe JVR, was associated with global cognitive function, and potentially with incident dementia.

The clinical application of optimized AT(N) classification in Alzheimer's clinical syndrome (ACS) and non-ACS conditions.

We aimed to assess the utility of AT(N) classification in clinical practice. We measured the cerebrospinal fluid levels of amyloid-ß (Aß) 42, Aß40, phosphorylated tau, total tau, and neurofilament light chain (NfL) in samples from 230 patients with Alzheimer's clinical syndrome (ACS) and 328 patients with non-ACS. The concordance of two A-markers (i.e., Aß42 alone and the Aß42/Aß40 ratio) was not significantly different between the ACS (87.4%) and non-ACS (74.1%) groups. However, the frequency of discordant cases with AAß42-alone+/AAß-ratio- was significantly higher in the non-ACS (23.8%) than in the ACS group (7.4%). The concordance of two N-markers (i.e., total tau and NfL) was 40.4% in the ACS group and 24.4% in the non-ACS group. In the ACS samples, the frequency of biological Alzheimer's disease (i.e., A+T+) in Ntau+ cases was 95% while that in NNfL+ cases was 65%. Reflecting Aß deposition and neurodegeneration more accurately, we recommend the use of AT(N) classification defined by cerebrospinal fluid AAß-ratioTNNfL in clinical practice.

Association between total cerebral small vessel disease score and cognitive function in patients with vascular risk factors.

Hypertension is the most important risk factor for cerebral small vessel disease (SVD). In this cross-sectional study, we tested the independent association of cerebral SVD burden with global cognitive function and each cognitive domain in patients with vascular risk factors. The Tokyo Women's Medical University Cerebral Vessel Disease (TWMU CVD) registry is an ongoing prospective, observational registry in which patients with any evidence of CVD in magnetic resonance imaging (MRI) and at least one vascular risk factor were consecutively enrolled. For SVD-related findings, we evaluated white matter hyperintensity, lacunar infarction, cerebral microbleeds, enlarged perivascular space, and medial temporal atrophy. We used the total SVD score as the SVD burden. They underwent the Mini-mental State Examination (MMSE) and Japanese version of the Montreal Cognitive Assessment (MoCA-J) global cognitive tests, and each cognitive domain was evaluated. After excluding patients without MRI T2* images and those with MMSE score <24, we analyzed 648 patients. The total SVD score was significantly associated with MMSE and MoCA-J scores. After adjustment for age, sex, education, risk factors, and medial temporal atrophy, the association between the total SVD score and MoCA-J score remained significant. The total SVD score was independently associated with attention. In conclusion, the total SVD score, cerebral SVD burden, was independently association with global cognitive function and attention. A strategy to reduce SVD burden will have the potential to prevent cognitive decline. A total of 648 patients with any evidence of cerebral small vessel disease (SVD) in MRI and at least one vascular risk factor underwent Mini-mental State Examination (MMSE) and Japanese version of the Montreal Cognitive Assessment (MoCA-J) global cognitive tests. The total SVD scores count the presence of each SVD-related findings (white matter hyperintensity, Lacunar infarction, cerebral microbleeds and enlarged perivascular space), ranging from 0 to 4, as the SVD burden. Total SVD scores were significantly associated with MoCA-J scores (r = -0.203, P < 0.001). After adjustment for age, sex, education, risk factors, and medial temporal atrophy, the association between the total SVD score and global cognitive scores remained significant.

Neuropsychological Profile of Early Cognitive Impairment in Cerebral Small Vessel Disease.

INTRODUCTION: The neuropsychological feature of vascular mild cognitive impairment is a deficit of the frontal-subcortical circuit; however, the features in the early stage are not consistent. In the present study, we aimed to investigate the neuropsychological features of the very early stage of cognitive impairment with cerebral small vessel disease (CSVD) and to elucidate the cognitive differences among CSVD subtypes. METHODS: A comprehensive neuropsychological test battery was applied to nondemented subjects scoring below the cutoff point 26 of the Japanese version of the Montreal Cognitive Assessment. After factor analysis was conducted to identify covert cognitive factors in the battery, correlation analyses were performed between the factors and CSVD subtypes: white matter hyperintensity (WMH), lacunar infarcts (LIs), cerebral microbleeds (CMBs), perivascular spaces, and cortical atrophy. RESULTS: Among the 465 recruited patients, 139 underwent a full neuropsychological test battery. Through factor analysis, the following three factors were extracted: executive function, memory, and attention. Of the CSVD features, total WMH was correlated with executive function and memory, whereas deep WMH was correlated with memory alone. Of the CSVD subtypes, LIs and CMBs were correlated only with executive function. Frontal and posterior atrophy were correlated with memory and attention, whereas medial temporal atrophy was correlated with memory alone. CONCLUSIONS: Executive dysfunction accompanied by subtle impairment of memory and processing speed was the main feature of neuropsychological profiles in the subjects with CSVD, even in the very early stage. Furthermore, each CSVD feature and focal cerebral atrophy are associated with cognitive impairment.

[MRI arterial spin labeling is useful for diagnosing recovery from nonconvulsive status epilepticus with sustained periodic discharges].

A 75-year-old man with a history of temporal lobe epilepsy (treated with levetiracetam) was transferred to our hospital because of loss of consciousness. At admission, he was drowsy and exhibited myoclonus on the left side of face. We established a diagnosis of status epilepticus and started treatment with levetiracetam, fosphenytoin, and midazolam. FLAIR and DWI showed hyperintensity in the right cerebral cortex. Electroencephalography (EEG) showed lateralized periodic discharges (LPDs) at the right hemisphere, indicative of non-convulsive status epilepticus (NCSE). He regained consciousness after treatment with anti-epileptic drugs but showed persistent LPDs in EEG. MRI arterial spin labeling (ASL) showed normal perfusion in the right hemisphere; therefore, he was deemed to have recovered from status epilepticus and transferred to the rehabilitation hospital. MRI ASL is useful for diagnosing recovery from NCSE irrespective of sustained periodic discharges on EEG.

p.N345K mutation in TARDBP in a patient with familial amyotrophic lateral sclerosis: An autopsy case.

We report the neuropathology of a patient with a family history of amyotrophic lateral sclerosis (ALS) and a p.N345K mutation in the transactivation response DNA-binding protein 43 kDa (TDP-43) gene (TARDBP). A 62-year-old man had bulbar palsy with progressive weakness in the extremities. Neurological examination revealed evident upper motor neuron signs and lower motor neuron involvement corroborated by needle electromyography. The patient was diagnosed as having probable ALS according to the revised El Escorial diagnostic criteria and was eventually diagnosed with familial ALS. At 65 years of age, respiratory failure became critical, and artificial ventilation was initiated. At 70 years of age, the patient died from a urinary tract infection. Histopathological investigation showed Bunina bodies in the remaining motor neurons and anterolateral funicular myelin pallor in the spinal cord. TDP-43-positive cytoplasmic inclusions were quite rare in the spinal cord motor neurons, being predominantly present in the glial cells (especially astrocytes) of the spinal cord anterior horn. Although the reason for the preferential vulnerability of spinal glial cells to TARDBP mutations remains unclear, our findings indicate that TARDBP p.N345K mutation could have an influence on the topography of TDP-43 aggregation.

Ischemic Stroke due to Virologically-Confirmed Varicella Zoster Virus Vasculopathy: A Case Series.

BACKGROUND: Limited data are available regarding the characteristics and prognosis of patients with stroke due to varicella zoster virus (VZV) vasculopathy. METHODS: We studied 4 patients (2 men and 2 women; age, 38-63 years) from a single center who developed acute ischemic stroke due to VZV vasculopathy. The virological diagnosis was confirmed by detecting VZV DNA and/or the IgG antibody to VZV in the cerebrospinal fluid. RESULTS: Three patients were taking immunosuppressive agents, including prednisolone and/or methotrexate, at baseline. Each patient had a characteristic skin rash prior to stroke, with the interval from rash to stroke onset ranging from 13 to 122 days. Two patients experienced antecedent cranial nerve palsies; one had the third, seventh, ninth, and 10th nerve palsies and the other had the fourth nerve palsy before stroke. Cerebral infarctions were located in the anterior circulation lesion (n = 1), in the posterior circulation lesion (n = 2), and in both lesions (n = 1). Intracranial arterial stenosis was only identified in one patient on magnetic resonance angiography. A high plasma d-dimer level was detected in 1 patient, whereas high ß-thromboglobulin and platelet factor 4 levels were detected in 2 patients. As a result of combined therapies with acyclovir, steroid, and antithrombotic agents, neurological symptoms markedly improved in 3 patients, whereas 1 patient was left with moderate hemiplegia. CONCLUSIONS: Cranial nerve palsies may be prodromal symptoms of VZV-associated stroke. Increased levels of thrombotic markers may support the use of antithrombotic agents, although the benefit of combined treatment should be determined through larger studies.

Three-Dimensional Computed Tomographic Analysis for Comminution of Pertrochanteric Femoral Fracture: Comminuted Anterior Cortex as a Predictor of Cutting Out.

BACKGROUND: Fixed angle sliding hip screw devices allow controlled impaction between the head neck fragment and the femoral shaft fragment in the surgical treatment of pertrochanteric fractures. This study was performed to evaluate the frequency and pattern of comminution at the fracture site, which may prevent the intended impaction. MATERIALS AND METHODS: Three-dimensional computed tomography was used to investigate 101 pertrochanteric fractures treated with fixed angle sliding hip screw devices, with emphasis on the comminuted cortex. A comminuted fracture was defined as a fracture that had a third fracture fragment at the main fracture line. RESULTS: There were 40 fractures without comminution and 61 with comminution. All 61 comminuted fractures had a comminuted posterior cortex, and 3 of 61 fractures also had comminution at the anterior cortex. The prevalence of cutting out of the implant from the femoral head was significantly higher in cases involving comminution at both the posterior and anterior cortices than in cases involving comminution only at the posterior cortex (66.7 % and 3.4 %, p < 0.0001). CONCLUSION: The posterior cortex was comminuted in 60.4% of pertrochanteric fractures and the anterior cortex in 3.0%. Intended impaction at the fracture site could not be obtained at any cortex in cases with comminution at both the anterior and posterior cortices; comminution at the anterior cortex may be a predictor of cutting out.

Sensitivity of hepatitis C virus core antigen and antibody combination assays in a global panel of window period samples.

BACKGROUND: Hepatitis C virus (HCV) antigen and antibody combination assays have been launched as a cost-effective alternative to nucleic acid testing (NAT) for reducing the antibody-negative window period (WP). Later, a HCV antigen chemiluminescence immunoassay (CLIA) became available. STUDY DESIGN AND METHODS: A panel composed of 337 HCV NAT-yield samples that were characterized for viral load (VL) and genotype was used to compare the sensitivity of two combination enzyme-linked immunosorbent assays (Monolisa, Bio-Rad; and Murex, formerly Abbott) and a HCV antigen CLIA (Abbott). Analytic sensitivity was compared with HCV RNA detection using Ultrio (Grifols) by testing serial dilutions of 10 genotype (gt)1 to gt4 samples. RESULTS: HCV antigen CLIA detected 92.4% of samples, whereas Monolisa and Murex detected 38.3 and 47.5%, respectively. In the HCV RNA VL range of 10(5) to 10(7) IU/mL, Monolisa and Murex detected 38% to 56% of gt1, 85% to 78% of gt2, and 21% to 37% of gt3. The overall geometric mean 50% limit of detection (range) of Ultrio on gt1 to gt4 dilution series was 3.5 (1.2-7.7) copies/mL, compared to 3.3 × 10(6) (4.4 × 10(5) -2.7 × 10(7) ), 3.4 × 10(6) (2.2 × 10(5) -4.2 × 10(7) ), and 2728 (415-7243) copies/mL for Monolisa, Murex, and HCV antigen CLIA, respectively. CONCLUSION: Analytical sensitivity of NAT was on average 1 million- and 780-fold higher than combination assays and HCV antigen CLIA, respectively. Relative sensitivities of combination assays differed for genotypes with Murex being more sensitive for gt1 and gt3 and Monolisa more sensitive for gt2. Although being less sensitive than NAT, combination assays could be considered in resource-limited settings since they detect 38% to 47% of seronegative WP donations.

Hepatitis B virus infection in hemodialysis patients in Japan: Prevalence, incidence and occult hepatitis B virus infection.

AIM: A survey of hepatitis B virus (HBV) infection in hemodialysis (HD) patients was conducted to determine the burden and risk of infection and to suggest preventive measures against HBV infection among HD patients at nine hospitals in Hiroshima, Japan, from 1999 to 2003. METHODS: HBV markers were investigated for 1860 HD patients. The prevalence, incidence of HBV and prevalence of occult HBV were calculated. RESULTS: The prevalence of hepatitis B surface antigen (HBsAg) was 2.6%, the positive rate of anti-hepatitis B core (HBc) was 20.6% and that of anti-hepatitis B surface (HBs) was 11.7%. Among 1372 patients who started HD after the approval of erythropoietin in Japan in 1991, the prevalence of HBsAg was 2.1%. The incidence rate of HBsAg positivity was 0/1000 person-years and the incidence of anti-HBc was 0.3/1000 person-years. Among 1812 HBsAg negative patients HBV DNA was detected in two: one case was negative for anti-HBc and anti-HBs, and the other was only positive for anti-HBc. Prevalence of occult HBV was 0.11%. CONCLUSION: The incidence rate of HBV was much lower than that of hepatitis C virus (HCV) in the same cohort. We supposed that the discrepancy between incidence rate of HBV and that of HCV was caused by the difference of their carrier rates and of their characteristics for persistent infection. So, we concluded that it is prerequisite to grasp the burden of HBV carriers in the group to prevent new HBV infections in HD patients.

Characterizing the normative profile of 18F-FDG PET brain imaging: sex difference, aging effect, and cognitive reserve.

The aim of this study was to investigate findings of positron emission tomography with 18F-fluorodeoxyglucose (18F-FDG PET) in normal subjects to clarify the effects of sex differences, aging, and cognitive reserve on cerebral glucose metabolism. Participants comprised 123 normal adults who underwent 18F-FDG PET and a neuropsychological battery. We used statistical parametric mapping (SPM8) to investigate sex differences, and aging effects. The effects of cognitive reserve on 18F-FDG uptake were investigated using years of education as a proxy. Finally, we studied the effect of cognitive reserve on the recruitment of glucose metabolism in a memory task by dichotomizing the data according to educational level. Our results showed that the overall cerebral glucose metabolism in females was higher than that in males, whereas male participants had higher glucose metabolism in the bilateral inferior temporal gyri and cerebellum than females. Age-related hypometabolism was found in anterior regions, including the anterior cingulate gyrus. These areas are part of the attentional system, which may decline with aging even in healthy elderly individuals. Highly educated subjects revealed focal hypermetabolism in the right hemisphere and lower recruitment of glucose metabolism in memory tasks. This phenomenon is likely a candidate for a neural substrate of cognitive reserve.

Presenting neuropsychological testing profile of autopsy-confirmed frontotemporal lobar degeneration.

AIMS: We aimed to investigate how neuropsychological test measures at presentation might differentiate frontotemporal lobar degeneration (FTLD) from Alzheimer's disease (AD). METHODS: We compared autopsy-confirmed FTLD and definite AD with Clinical Dementia Rating ≤1. Factor scores and t values of each neuropsychological test measure were compared between FTLD and AD patients. Logistic regression analyses were applied to identify independent predictors within test measures for the differentiation of FTLD from AD. RESULTS: Factor analyses showed that the memory domain was more severely impaired in AD than in FTLD, whereas the language and attention domains were more severely impaired in FTLD than in AD. Multiple logistic regression analysis showed that Letter Fluency, Boston Naming Test and delayed memory recall remained independent predictors of FTLD compared to AD. However, test measures did not discriminate between FTLD-tau and FTLD-ubiquitin. CONCLUSION: We confirm that memory and language function tests discriminate between FTLD and AD.

Early neuropsychological discriminants for Lewy body disease: an autopsy series.

OBJECTIVE: To determine which neuropsychological test measures and which symptoms at presentation might best differentiate dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). METHODS: Cases were from the Columbia University Alzheimer's Disease Research Center, and included cases with pathological diagnosis of pure DLB (n=12), mixed DLB and AD (DLB+AD n=23) and pure AD (n=89) who had Clinical Dementia Rating 0, 0.5 or 1 at their first visit. Clinical symptoms and neuropsychological test measures were compared for pure DLB, DLB+AD and pure AD using univariate analysis of covariance and separate logistic regression analyses. RESULTS: Visual hallucinations, illusions and extrapyramidal tract signs were more frequent as clinical features of the early stage of pure DLB compared with AD. The pure DLB patients showed more impaired visuospatial function than pure AD or DLB+AD patients whereas memory function was more severely impaired in pure AD or DLB+AD than in pure DLB. Analysis of memory subscores suggested that failure of retrieval was the major contributor to the memory deficit of DLB. Multiple logistic regression analysis showed that visuospatial function and delayed memory recognition were independent predictors of pure DLB from pure AD and from DLB+AD. But test measures did not discriminate between DLB+AD and pure AD. CONCLUSIONS: Visuospatial function was more affected in pure DLB than in AD while memory retrieval deficit was more affected in AD than in pure DLB, in the early stages of dementia. However, DLB+AD did not show significant neuropsychological difference from pure AD.

Polymer-bound pyrene-4,5,9,10-tetraone for fast-charge and -discharge lithium-ion batteries with high capacity.

Organic rechargeable batteries have received significant research interest from the viewpoints of structural diversity and sustainability of electrode materials. We designed core structures of organic cathode materials for lithium-ion (Li-ion) batteries based on density functional theory (DFT) calculations, which indicated that six-membered cyclic 1,2-diketones serve as excellent core structures because of the high redox energy change resulting from favorable coordination of the oxygen atoms to Li and the aromaticity of the reduced form. Here, we show that the Li-ion battery composed of pyrene-4,5,9,10-tetraone (PYT), which has two six-membered cyclic 1,2-diketone units, bound to polymethacrylate exhibits remarkable charge-discharge properties with a high specific capacity of 231 mAh/g, excellent rechargeability (83% of the capacity retained after 500 cycles), and charge-discharge ability (90% of the capacity at 30 C as compared to 1 C) in the LiNTf(2)/tetraglyme ionic-liquid system.

Follow up of the 987 blood donors found with hepatitis C virus infection over 9-18 years.

AIM: To follow up blood donors found with hepatitis C virus (HCV) infection, to improve the outcome by antiviral treatments. METHODS: Between 1991 and 2001, 3377 of the 1 925 860 donors (0.18%) were found to have HCV infection at the Hiroshima Red Cross Blood Center in Japan. Of them, 987 were able to be followed regularly over 9-18 years until 2009, and received antiviral treatments as required. RESULTS: At the start, chronic hepatitis was diagnosed in 541 (54.8%), cirrhosis in five (0.5%) and hepatocellular carcinoma (HCC) in one (0.1%), whereas the remaining 439 (44.5%) had persistently normal aminotransferase levels (PNAL). Hospital visits were terminated voluntarily in 24.3% within the first year, 46.8% by 10 years and 50.9% by 17 years. Liver disease improved in 178 (18.0%), remained stable in 606 (61.4%) and aggravated in 170 (17.2%). Of the 541 donors with chronic hepatitis, HCC developed in 28 (5.2%) and cirrhosis in 11 (2.0%), whereas HCV infection was cleared in 107 (19.8%) by antiviral treatments. In addition, HCV infection resolved in 54 of the 439 donors (12.3%) with PNAL after they had developed chronic hepatitis and received treatments. In donors with chronic hepatitis, the cumulative incidence of HCC was 4.1% at 10 years. By multivariate analysis, age and diagnosis of chronic hepatitis at the entry were found to be independent risk factors for the development of HCC. CONCLUSION: Individuals with undiagnosed HCV infection need to be identified and receive medical care. They have to be motivated to merit from this health-care program.

Total numbers of undiagnosed carriers of hepatitis C and B viruses in Japan estimated by age- and area-specific prevalence on the national scale.

OBJECTIVE: To estimate total numbers of undiagnosed carriers of hepatitis C virus (HCV) and hepatitis B virus (HBV) in Japan. METHODS: Area- and age-specific prevalence of HCV as well as HBV was determined in the first-time blood donors [20-39 years (n = 2,429,364)] and examinees of periodical health check-ups [40-74 years (6,204,968 for HCV and 6,228,967 for HBV)] in Japan. Prevalence in adolescents [5-19 years (79,256 for HCV and 68,792 for HBV)] was determined in a single prefecture, and that of HCV in the elderly (≥ 75 years) was estimated by the exponential model. HBV infection was determined by the detection of hepatitis B surface antigen, and HCV infection by either the algorithm or assuming persistent infection in 70% of the individuals with antibody to HCV. RESULTS: Of the total population of 127,285,653 in 2005, 807,903 (95% CI 679,886-974,292) were estimated to be infected with HCV at a carrier rate of 0.63%, and 903,145 (837,189-969,572) with HBV at that of 0.71%. CONCLUSION: Accurate estimation of undiagnosed HCV and HBV carriers in the general population would help to predict the future burden of liver disease, and take appropriate measures for improving healthcare.

Interferon alone or combined with ribavirin for acute prolonged infection with hepatitis C virus in chimpanzees.

Infection with hepatitis C virus (HCV) persisted for longer than 29 weeks in 2 chimpanzees after they had been inoculated with it experimentally. One of them (C-210) received short-term subcutaneous interferon-α (IFN-α) 6 million units (MU) daily for 7 days at week 29. He cleared HCV RNA from the serum and remained negative for it during 25 weeks after the withdrawal of IFN. The other (C-224) did not respond to 2 courses of a short-term IFN monotherapy at weeks 20 and 23. Twelve weeks thereafter, he received IFN-α 3 MU daily for 2 weeks and then 3 times a week for 14 weeks combined with oral ribavirin 600 mg daily during 16 weeks. HCV RNA disappeared from the serum and stayed negative until the last follow-up 24 weeks after the completion of combination therapy.