Association of IL28B rs8099917 genotype and female sex with spontaneous clearance of hepatitis C virus infection: a Japanese cross-sectional study.

Hepatitis C virus (HCV) infection is a serious global health problem. Previous studies have suggested that the interleukin 28B (IL28B) rs8099917 genotype is related to spontaneous clearance of HCV in Caucasian populations. Our objective was to investigate the association of the IL28B rs8099917 genotype with spontaneous clearance of HCV by community-dwelling Japanese. A cross-sectional community-based population study of 993 Japanese residents was conducted. Based on anti-HCV antibody and HCV RNA levels, 50 subjects were assigned to the spontaneous-clearance group, 155 to the chronic-infection group, and 788 to the control group. Logistic regression analysis was done to examine the roles of the IL28B rs8099917 genotype and sex. To analyze the interactions between these factors, an "IL28B rs809991 genotype × sex" interaction term was included in the multivariate analysis. Significantly more subjects in the spontaneous-clearance group than in the chronic-infection group had the favorable IL28B rs8099917 genotype and were female. Multivariate logistic regression analysis extracted the favorable IL28B rs8099917 TT genotype (odds ratio [OR] 9.39; 95% confidence interval [CI], 2.16-40.83, P = 0.003) and female sex (OR, 2.27; 95% CI, 1.16-4.45, P = 0.017) as factors contributing to the spontaneous clearance of HCV. No significant interaction was found between the IL28B rs8099917 genotype and sex (P for interaction = 0.428). Both the favorable IL28B rs8099917 genotype and female sex were associated with the spontaneous clearance of HCV in this Japanese population.

Bioelectrical Impedance Analysis (BIA) of the association of the Japanese Kampo concept "Suidoku" (fluid disturbance) and the body composition of women.

BACKGROUND: In Japanese Kampo medical practice, suidoku (fluid disturbance) is one of the most important concepts for selecting the proper medication. Suidoku is an excessive or uneven distribution of fluid that is indicated by splashing sounds and pitting edema. However, few objective reports about suidoku have been published. Bioelectrical impedance analysis (BIA) uses resistance values obtained from weak electrical currents to estimate body composition, including intracellular and extracellular water and muscle and fat mass. In this study, we used BIA to search for objective factors that can discriminate the various types of suidoku. METHODS: Two hundred twenty-nine patients who visited the Kampo Medicine Clinic of Kyushu University Hospital from June 2010 to August 2015 were divided into non-suidoku (n = 180, 80 male and 100 female), splashing sound (n = 32, 8 male and 24 female) and edema groups (n = 17, 5 male and 12 female). Body composition values were taken from the electronic medical records of InBody730 (a vertical, segmental, multi-frequency analyzer by InBody, Tokyo Japan) testing done at the initial visit. Various parameters of the body composition values of female in the non-suidoku and suidoku groups (splashing sound and edema groups) were compared: there were too few male patients to provide significance. RESULTS: The age and body weight were significantly lower in the splashing sound group than in the non-suidoku group (p < 0.05). In contrast, the body weight of the edema group was significantly heavier than that of the non-suidoku group (p < 0.05). In ROC analysis, the percent Body Fat ≤ 27.8 %, Muscle Mass Index of the Trunk ≤ 6.5 kg/m2, VFA (Visceral fat area) ≤ 5.4 and BMI ≤ 19.2 kg/m2 were associated with splashing sound, and Muscle Mass Index of Legs ≥ 4.8 kg/m2 and BMI ≥ 21.4 kg/m2 were associated with edema. CONCLUSION: Our data suggest that the use of this type of BIA to estimate body composition would be a useful tool for the diagnosis of suidoku for women.

The association between objective tongue color and endoscopic findings: results from the Kyushu and Okinawa population study (KOPS).

BACKGROUND: The relation between tongue color and gastroesophageal disease is unclear. This study was done to investigate the associations between tongue color (TC), endoscopic findings, Helicobacter.pylori infection status, and serological atrophic gastritis (SAG). METHODS: The participants were 896 residents of Ishigaki Island, Okinawa, aged 28-86 years. The tongue was photographed, esophagogastroduodenoscopy was done, and serum antibody to H.pylori was measured. SAG was defined as a serum Pepsinogen (PG)Ilevel ≤70 ng/ml and a PGI/IIratio ≤3.0. TC was measured by the device-independent international commission on Illumination 1976 L*a*b* color space standards at four points: (1) edge, (2) posterior, (3) middle, and (4) apex. We also calculated the ratio of the tongue edge to the three other measured points to examine the association between the coating of the tongue and the endoscopic and laboratory findings. RESULTS: Participants were excluded who had two or more endoscopic findings (n = 315) or who had SAG without seropositivity to H.pylori (n = 33). The remaining 548 participants were divided into three groups: SAG and seropositive to H.pylori (n = 67), seropositive to H.pylori alone (n = 56), and without SAG and seronegative for H.pylori (n = 425). We divided 425 residents into a single endoscopic finding positive group (n = 207) and a negative group, which served as a control (n = 218). The most frequent single endoscopic finding was esophageal hernia (n = 110), followed by erosive esophagitis (n = 35) and erosive gastritis (EG) (n = 45). EH was significantly associated with TC (2b*/1b*) (P < 0.05). EG was significantly associated with TC (3a*, 3b*) (P < 0.05). Seropositivity to H.pylori was significantly associated with TC (3 L*, 3 L*/1 L*) (P < 0.05, <0.01), and seropositivity to both H.pylori and SAG was significantly associated with TC (3 L*/1 L*) (P < 0.05). Multivariate analysis extracted TC (3a*, 3b*) as an independent factor associated with a differential diagnosis of EG (Odds ratio (OR) 2.66 P = 0.008, OR 2.17 P = 0.045). CONCLUSIONS: The tongue body color of the middle area reflects acute change of gastric mucosa, such as erosive gastritis. Tongue diagnosis would be a useful, non-invasive screening tool for EG.

Therapeutic drug monitoring of telaprevir in chronic hepatitis C patients receiving telaprevir-based triple therapy is useful for predicting virological response.

OBJECTIVES: This prospective, pharmacokinetic study was done to investigate the impact of telaprevir plasma trough concentration (Ctrough) in the early stage of treatment on the response to telaprevir-based triple therapy for chronic hepatitis C patients. METHODS: Participants were 70 chronic hepatitis C patients infected with genotype 1. All patients received 12 week triple therapy that included telaprevir (2250 mg/day), pegylated interferon-α2b (pegylated-IFNα2b) (60-150 µg/week) and ribavirin (600-1000 mg/day) followed by a 12 week dual therapy that included pegylated-IFNα2b and ribavirin. Plasma telaprevir Ctrough was determined by a validated assay using HPLC at days 3, 7 and 14. The study was registered as a clinical trial on the University Hospital Medical Information Network (ID 000009656). RESULTS: The rates of undetectable hepatitis C virus RNA at week 4 [rapid virological response (RVR)] and at 24 weeks after therapy [sustained virological response (SVR)] were 71.4% and 82.9%, respectively. Of the patients with RVR, 90% achieved SVR. The mean telaprevir Ctrough levels at days 3, 7 and 14 of SVR patients (2.748, 2.733 and 2.999 µg/mL, respectively) were significantly higher than those of non-SVR patients (1.616, 1.788 and 2.314 µg/mL, respectively) (all P < 0.05). Multiple logistic regression analysis of possible predictors of SVR extracted higher telaprevir Ctrough at day 3 (OR 1.012 by 0.001 µg/mL, P < 0.0001) and interleukin 28B (rs8099917) TT allele (OR 6.16 versus non-TT alleles, P < 0.0001). CONCLUSIONS: Therapeutic drug monitoring of telaprevir in the early stage of treatment is useful in clinical practice for predicting the virological response of patients receiving telaprevir-based triple therapy.

Nocturnal difference in the ultra low frequency band of heart rate variability in patients stratified by Kampo medicine prescription.

BACKGROUND: The Yo/Yin concept is fundamental to making a Kampo (sho) diagnosis and may be deeply related to the autonomic nervous system. There is, however, little objective data to confirm the validity of these concepts. METHODS AND RESULTS: After diagnosis using standardized Kampo techniques, 20 men and 67 women (mean age, 52.4 years) for whom the prescribed Kampo medication was effective were judged to be correctly classified as Yo- (n=49) or Yin-sho (n=38) and enrolled. Autonomic nervous function was assessed at first visit using HRV obtained from 24-h Holter ECG. Nocturnal ultra low frequency-1 (ULF-1, 0.0001-0.0003 Hz) and ULF-2 (0.0003-0.003 Hz) were significantly higher in the Yin-sho than in the Yo-sho group (P=0.030, P=0.016), suggesting a higher variation of autonomic nervous activity according to sleep stage. On multivariate analysis BMI (≥ 23.0 kg/m(2)) and ULF-1 (≥ 1,150 ms(2)) were identified as independent factors associated with a differential diagnosis of Yo- or Yin-sho (odds ratio [OR], 11.63, P=0.002; OR, 0.30, P=0.038, respectively). When the sleep period was divided into 3 phases, the ULF-1 of the Yin-sho group was significantly higher than that of the Yo-sho group in the late phase of sleep (P=0.023). CONCLUSIONS: On heart rate variability analysis there was a sleep stage-related difference in the autonomic nervous activity of patients treated with standard Yo- and Yin-sho Kampo medicines.

A case of successful hepatitis C virus eradication by 24 weeks of telaprevir-based triple therapy for a hemophilia patient with hepatitis C virus/human immunodeficiency virus co-infection who previously failed pegylated interferon-α and ribavirin therapy.

In Japan, the human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection of some patients with hemophilia was caused by the transfusion of imported blood products, such as unheated coagulation factor. With the development of antiretroviral therapy (ART) for HIV, chronic HCV infection has become a major cause of liver disease and mortality for hemophiliac patients coinfected with HCV/HIV. Data is limited regarding the efficacy and safety of antiviral therapy with the HCV protease inhibitor telaprevir (TVR) in combination with pegylated interferon-α (PegIFN-α) and ribavirin (RBV) for hemophilia patients coinfected with HCV/HIV. We report a case of a Japanese patient with hemophilia and HCV/HIV coinfection who had partial response to prior to PegIFN-α and RBV therapy. This is the first published report of 24-week TVR-based triple therapy for a hemophilia patient coinfected with HCV/HIV. The patient had HCV genotype 1a infection with a high viral load. His single-nucleotide polymorphism of the interleukin 28B (rs8099917) gene was the TT major allele. He presented with undetectable HIV RNA and a high CD4(+) T cell counts by taking ART including tenofovir, emtricitabine and raltegravir. He was again treated for HCV with TVR plus PegIFN-α2b and RBV for the first 12 weeks, followed by the continuation of PegIFN-α2b and RBV for 12 additional weeks while continuing ART. He had rapid virological response and achieved sustained virological response with the 24-week treatment. No serious adverse events such as skin rash, severe anemia or exacerbated bleeding tendency were observed, only a mild headache. No dose adjustment was necessary when tenofovir and raltegravir were used in combined with TVR, and no HIV breakthrough was observed. TVR-based triple therapy with ART could can an effective treatment for hemophilia patients coinfected with HCV (genotype 1)/HIV regardless of prior response. TVR can be used in combination with tenofovir, emtricitabine and raltegravir for patients with hemophilia. Furthermore, patients with undetectable HCV RNA at week 4 could be successfully treated with a 24-week regimen.

The Impact of an Undergraduate Community-Based Medical Education Program in a Japanese Urban City.

INTRODUCTION:  With an aging global population posing healthcare challenges, especially in community healthcare, training professionals for community healthcare remains a global educational challenge, including in Japan. While previous research shows increased student interest in community healthcare through practical experiences, the focus has primarily been on rural areas, leaving a gap in understanding urban-based community medical education. This study aimed to evaluate the impact of urban community-based medical education on students' understanding and attitudes toward community healthcare. METHODS:  This study was conducted at Kyushu University in Fukuoka City, the sixth-largest city in Japan. For fifth-grade medical students, a community-based medical education program is mandatory, with a one-week schedule that includes orientation, one day in a clinic, and three days in a community hospital. The program aimed to expose students to various healthcare settings, emphasizing outpatient care, inpatient management, home health care, home nursing, and rehabilitation. A self-administered questionnaire referencing the Model Core Curriculum for medical education was administered immediately before and after the program, and the differences in students' perceptions were assessed using the Student's t-test. RESULTS:  Findings from 188 students completing both pre- and post-program questionnaires revealed significant improvements in perceptions of students' knowledge and skills related to community healthcare. After the training, there was a noteworthy positive shift in attitudes toward community healthcare and increased interest in primary care physicians as a career choice. Although students maintained a preference for urban areas, there was a notable inclination towards rural settings. The study highlights the program's success in enhancing students' understanding and positive attitudes toward community healthcare within an urban context. It challenges prior notions regarding work-life balance and urban-rural preferences in career choices. CONCLUSIONS:  Urban community-based medical education significantly improved students' perceptions and attitudes toward community healthcare. It offers valuable insights for curriculum planners, emphasizing the need for continued research into sustained effects and broader applicability.

The Presence of Ganglionic Acetylcholine Receptor Antibodies in Sera from Patients with Functional Gastrointestinal Disorders: A Preliminary Study.

BACKGROUND: Functional gastrointestinal disorders (FGIDs), including functional dyspepsia (FD) and irritable bowel syndrome (IBS), are characterized by chronic and recurrent gastrointestinal symptoms. Clinically, FD and IBS often resemble gastrointestinal dysmotility caused by autoimmune autonomic neuropathy. We examined the seropositive frequency of autoantibodies against ganglionic nicotinic acetylcholine receptors (gnAChRs) in patients presenting with FGIDs. OBJECTIVE: To elucidate the seropositivity of gnAChR antibodies and the clinical features of seropositive FD and IBS. MATERIALS AND METHODS: We measured autoantibodies against the gnAChR α3 and ß4subunits using luciferase immunoprecipitation systems. Serum samples from patients with any autonomic symptoms were obtained from hospitals in Japan between January 2012 and August 2018 (1787 serum samples of 1381 patients). We selected FD and IBS patients and compared the clinical characteristics and prevalence of autonomic symptoms between those with seropositive and seronegative IBS and FD. RESULTS: Nine IBS and two FD cases (one comorbid case with IBS) were found. We found four patients (36.4%) in whom gnAChR antibodies were positive in these eleven patients. Sicca symptoms were observed in three of four cases (75%) of seropositive FGID compared with zero of seven cases (0%) of seronegative FGID. CONCLUSIONS: We found patients with gnAChR antibodies in FD and IBS patients. These data will be valuable for elucidating the pathophysiology of these FGIDs and developing new treatment strategies.

Successful treatment of restless legs syndrome accompanied by headaches for 30 years with herbal prescriptions containing Paeoniae Radix: A case report.

BACKGROUND: Restless legs syndrome (RLS) is a neurological disorder that causes unpleasant symptoms in the legs when resting, which are relieved by movement. Pharmacotherapy is the standard treatment. However, current treatment provides only symptomatic relief and may result in adverse effects with long-term use. Treatment protocols using herbal medicines have emerged to compensate for this limitation. CASE PRESENTATION: A 70-year-old Asian woman visited our hospital with worsening headaches that had persisted for 30 years. Her headaches were aggravated by night-time lower-extremity discomfort. The patient was diagnosed with RLS based on the 2012 Revised International Restless Leg Syndrome Study Group Diagnostic Criteria (IRIS). The patient was prescribed herbal medicines, Shihogyeji-tang, Gyejibokryeong-hwan, and Jakyakgamcho-tang, all of which contain Paeoniae Radix. Fourteen days after starting herbal medicine treatment, the IRIS score decreased from 30 to 18. The patient experienced less leg discomfort. Moreover, her sleep time increased, and her headaches resolved. After 28 days of herbal treatment, the IRIS score decreased to 9. Importantly, the patient reported no sleep disturbance or headaches. Subsequently, conventional medications were discontinued. The patient remained stable (IRIS score: 9-10). Herbal treatment was discontinued on day 163. At the last follow-up, (day 364), the patient has not reported any symptom recurrence. CONCLUSIONS: We described a female patient with a 30-year history of RLS symptoms and related sleep disturbances that induced chronic uncontrolled headaches, who experienced improvements shortly after using herbal medicines containing Paeoniae Radix. Conventional medications were discontinued and the patient had no recurrence of symptoms. Considering these, herbal medicines containing Paeoniae Radix may be a suitable alternative treatment for RLS and its related symptoms.

Proposal for effective treatment of Shiga toxin-producing Escherichia coli infection in mice.

Previously, we reported that minocycline, kanamycin and norfloxacin improved the survival rate in the E32511 model that we developed (FEMS Immunol Med Microbiol 26, 101-108, 1999), but fosfomycin did not. In this study, we investigated the effectiveness of azithromycin (AZM) against Stx2d-producing EHEC O91:H21 strain B2F1 or Stx2c-producing Escherichia coli strain E32511 treated with mitomycin C in vivo. Recently, we reported the effectiveness of AZM in our model and AZM strongly inhibited the release of Stx2c from E32511 in vitro (PLOS ONE e58959, 2013). However, it was very difficult to completely eliminate E32511 in the mouse feces by treatment with AZM alone. In this report, only AZM or Daio effectively promoted survival of mice infected with B2F1 compared to untreated mice. Furthermore, Daio inhibited the colonization of GFP-expressing B2F1 in the mouse intestine. Similarly, a combination of AZM and Daio in the E32511-infected mice reduced E32511 in the mouse feces and significantly improved survival.

Metabolic changes in the plasma of mild Alzheimer's disease patients treated with Hachimijiogan.

Background: Alzheimer's disease (AD), the most prevalent form of dementia, is a debilitating, progressive neurodegeneration. Amino acids play a wide variety of physiological and pathophysiological roles in the nervous system, and their levels and disorders related to their synthesis have been related to cognitive impairment, the core feature of AD. Our previous multicenter trial showed that hachimijiogan (HJG), a traditional Japanese herbal medicine (Kampo), has an adjuvant effect for Acetylcholine estelase inhibitors (AChEIs) and that it delays the deterioration of the cognitive dysfunction of female patients with mild AD. However, there are aspects of the molecular mechanism(s) by which HJG improves cognitive dysfunction that remain unclear. Objectives: To elucidate through metabolomic analysis the mechanism(s) of HJG for mild AD based on changes in plasma metabolites. Methods: Sixty-seven patients with mild AD were randomly assigned to either an HJG group taking HJG extract 7.5 g/day in addition to AChEI or to a control group treated only with AChEI (HJG:33, Control:34). Blood samples were collected before, 3 months, and 6 months after the first drug administration. Comprehensive metabolomic analyses of plasma samples were done by optimized LC-MS/MS and GC-MS/MS methods. The web-based software MetaboAnalyst 5.0 was used for partial least square-discriminant analysis (PLS-DA) to visualize and compare the dynamics of changes in the concentrations of the identified metabolites. Results: The VIP (Variable Importance in Projection) score of the PLS-DA analysis of female participants revealed a significantly higher increase in plasma metabolite levels after HJG administration for 6 months than was seen in the control group. In univariate analysis, the aspartic acid level of female participants showed a significantly higher increase from baseline after HJG administration for 6 months when compared with the control group. Conclusion: Aspartic acid was a major contributor to the difference between the female HJG and control group participants of this study. Several metabolites were shown to be related to the mechanism of HJG effectiveness for mild AD.

Conventional and Kampo Medicine Treatment for Mild-to-moderate COVID-19: A Multicenter, Retrospective, Observational Study by the Integrative Management in Japan for Epidemic Disease (IMJEDI Study-observation).

Objective Patients in whom coronavirus disease 2019 (COVID-19) was suspected or confirmed between January 1, 2020, and October 31, 2021, were enrolled from Japanese hospitals in this multicenter, retrospective, observational study. Methods Data on the treatment administered (including conventional and Kampo medicine) and changes in common cold-like symptoms (such as fever, cough, sputum, dyspnea, fatigue, and diarrhea) were collected from their medical records. The primary outcome was the number of days without a fever (with a body temperature <37°C). The secondary outcomes were symptomatic relief and the worsening of illness, defined as the presence of a condition requiring oxygen inhalation. The outcomes of patients treated with and without Kampo medicine were compared. Patients We enrolled 962 patients, among whom 528 received conventional and Kampo treatment (Kampo group) and 434 received conventional treatment (non-Kampo group). Results Overall, after adjusting for the staging of COVID-19 and risk factors, there were no significant between-group differences in the symptoms or number of days being afebrile. After performing propensity score matching and restricting the included cases to those with confirmed COVID-19 who did not receive steroid administration and initiated treatment within 4 days from the onset, the risk of illness worsening was significantly lower in the Kampo group than in the non-Kampo group (odds ratio=0.113, 95% confidence interval: 0.014-0.928, p=0.0424). Conclusion Early Kampo treatment may suppress illness worsening risk in COVID-19 cases without steroid use. Further randomized controlled studies are needed to confirm the clinical benefit of Kampo medicine for COVID-19.

Insulin resistance undermines the advantages of IL28B polymorphism in the pegylated interferon alpha-2b and ribavirin treatment of chronic hepatitis C patients with genotype 1.

BACKGROUND & AIMS: Recent studies have suggested that insulin resistance exerts a strong influence on chronic hepatitis C virus (HCV) infection. We analyzed pretreatment factors useful for predicting sustained virological response (SVR), especially interleukin (IL) 28B polymorphism and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). METHODS: This cohort study consisted of 328 chronic hepatitis C patients with HCV genotype 1 who were treated for 48 weeks with pegylated interferon (PegIFN) α-2b and ribavirin (RBV). Genotyping of the polymorphisms in the IL28B gene region (rs8099917) on chromosome 19 was performed on DNA collected from each patient. RESULTS: No significant difference in IL28B genotype distribution was found according to HOMA-IR. Multivariate analysis identified the IL28B TT genotype (OR=5.97, 95% CI 2.15-16.55, p=0.0006) and the baseline HOMA-IR (OR=0.65, 95% CI 0.48-0.87, p=0.0044) as significant, independent pretreatment predictors of SVR. Receiver operating characteristic analyses to determine the optimal threshold values of HOMA-IR for predicting SVR showed that the areas under the curve (AUC) were high for both IL28B TT (AUC=0.774, HOMA-IR cut-off value: 2.45) and IL28B TG/GG genotypes (AUC=0.772, HOMA-IR cut-off value: 1.55). CONCLUSIONS: For HCV genotype 1, both IL28B and baseline HOMA-IR are independent pretreatment predictors of SVR in patients treated with PegIFNα-2b and RBV. Insulin resistance undermines the advantages of IL28B polymorphism to obtain SVR.

Raloxifene hydrochloride is an adjuvant antiviral treatment of postmenopausal women with chronic hepatitis C: a randomized trial.

BACKGROUND & AIMS: Early menopause in women with chronic hepatitis C virus (HCV) infection is associated with a low likelihood of a sustained virological response (SVR) in conjunction with their antiviral treatment. This is potentially related to their reduced estrogen secretion. The study was done to determine whether selective estrogen receptor modulator administration might improve the efficacy of the current standard of care (SOC) treatment, pegylated interferon (PegIFN) α2a plus ribavirin (RBV), for postmenopausal women. METHODS: One hundred and twenty-three postmenopausal women with genotype 1b chronic hepatitis C were randomly assigned to one of two treatment groups: raloxifene hydrochloride (RLX) (60 mg/day) plus SOC (PegIFNα2a 180 µg/week and RBV 600-1,000 mg/day) (n=62) or SOC only (n=61). Genotyping was performed of the polymorphism in the interleukin-28B (IL28B) gene region (rs8099917) of DNA collected from each patient. RESULTS: One RLX-treated patient discontinued RLX because of a systemic rash following 2 weeks of treatment. Twenty-four weeks after treatment, the SVR rate was significantly higher for RLX plus SOC patients (61.3%) than for SOC only patients (34.4%) (p=0.0051). Further, the SVR rate was significantly higher for RLX plus SOC patients with IL28B TT (72.5%) than for SOC only patients with IL28B TT (39.2%) (p=0.0014), but no such relationship was observed in patients carrying the minor IL28B allele. CONCLUSIONS: RLX improved the efficacy of SOC in the treatment of postmenopausal women with chronic hepatitis C. RLX shows promise as an adjuvant to the standard antiviral treatment of such patients.

[A case of hepatitis B virus/human immunodeficiency virus coinfection in a patient who achived hepatitis B surface antigen seroclearance after interferon therapy followed by antiretroviral therapy without developing immune reconstitution inflammatory syndrome].

Coinfection with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) is common worldwide. The current guidelines for the treatment of HIV infection recommend that HIV patients coinfected with HBV receive antiretoroviral therapy (ART) with two nucleoside analogs against HBV. However, an increase in liver enzymes that is usually attributed to HBV immune reconstitution inflammatory syndrome (IRIS) sometimes occurs in HBV/HIV-coinfected patients after the commencement of ART. We report a case of HBV/HIV-coinfection in which the chronic hepatitis B was successfully treated using interferon (IFN) therapy followed by ART without the development of IRIS. A Japanese man in thirties was referred to our hospital because of an acute HIV infection two months after the diagnosis of an acute HBV infection, which had progressed to a chronic HBV infection. The laboratory test results were as follows:hepatitis B surface antigen (HBsAg) positive, hepatitis B e antigen (HBeAg) positive, HBV DNA level of 8.8 Log copies/mL, HBV genotype A, alanine aminotransferase of 834 IU/L, HIV RNA level of 5 Log copies/mL, and a CD4+ T cell count of 437/microL. The initial treatment was natural IFNalpha therapy for chronic hepatitis B, and HBeAg seroclearance was achieved 20 weeks after the start of therapy. Four months after the end of IFN therapy for 24 weeks, ART including tenofovir and emtricitabine against HBV was commenced. Six months after starting ART, the patient's serum HBV DNA level had decreased and become undetectable and HBsAg seroclearance was achieved without an elevation in liver enzymes. The present case suggests that IFN therapy prior to ART contributes to a successful outcome for chronic hepatitis B patients coinfected with HIV, if the HIV status does not require the immediate start of ART.

Development of Versatile and Interactive Model Lessons in Kampo Medicine Education.

OBJECTIVE: To develop versatile and interactive model classes by generating the contents of Kampo classroom sessions that can be taught by instructors who are not familiar with Kampo medicine. METHODS: In 2018, we conducted Kampo classroom sessions among fourth-year medical students at Kyushu University in which we incorporated new content. A videotaped digest edition of the classes was sent to Kampo medicine instructors in medical schools throughout Japan. An online questionnaire was given to the instructors regarding effectiveness of the class content (Q1) and whether they would introduce the content in their classes (Q2). We modified the curriculum according to survey responses and conducted revised classroom sessions again in 2019. A second online survey was given and we finalized the model classes. We compared survey responses between staff and instructors (group A) and non-specialists in Kampo medicine (group B). RESULTS: In 2018, there were significant differences between groups A (44) and B (52) regarding a patient's story and case report (Q1). In 2019, there were significant differences between groups A (42) and B (54) regarding the case report using e-learning(Q1) and an instructor's experience (Q2). CONCLUSIONS: We propose that Kampo medicine classes should incorporate an instructor's experience and interactive case report presentation using e-learning.

An exploratory, open-label, randomized, multicenter trial of hachimijiogan for mild Alzheimer's disease.

Background: Alzheimer's disease (AD) is a progressive neurodegeneration and is the most prevalent form of dementia. Intervention at an early stage is imperative. Although three acetylcholinesterase inhibitors (AChEIs) are currently approved for the treatment of mild AD, they are not sufficiently effective. Novel treatments for mild AD are of utmost importance. Objective: To assess the effectiveness of hachimijiogan (HJG), a traditional Japanese herbal medicine (Kampo), in the treatment of mild AD. Methods: This exploratory, open-label, randomized, multicenter trial enrolled patients with mild AD whose score on the Mini Mental State Examination (MMSE) was over 21points. All participants had been taking the same dosage of AChEI for more than 3 months. The participants were randomly assigned to an HJG group taking HJG extract 7.5 g/day in addition to AChEI or to a control group treated only with AChEI. The primary outcome was the change from baseline to 6 months post treatment initiation on the Alzheimer's Disease Assessment Scale-cognitive component- Japanese version(ADAS-Jcog). The secondary outcomes were change from baseline of the Instrumental Activity of Daily Life (IADL), Apathy scale, and Neuropsychiatric Inventory (NPI) -Q score. Results: Among the 77 enrollees, the data of 69(34 HJG and 35 control)were available for analysis. The difference in the change of ADAS-Jcog from baseline to 6 months of the HJG and control groups was 1.29 (90% Confidence interval (CI), -0.74 to 3.32 p = 0.293). In the subgroup analysis, the differences in the change from baseline to 3 and 6 months for women were 3.70 (90% CI ,0.50 to 6.91, p = 0.059) and 2.90 (90% CI,0.09 to 5.71, p = 0.090), respectively. For patients over 65 years, the difference at 3 months was 2.35 (90%CI, 0.01 to 4.68 p = 0.099). No significant differences were found between the HJG and control groups in IADL score, Apathy scale, or NPI-Q score. Conclusion: Although not conclusive, our data indicate that HJG has an adjuvant effect for acetylcholinesterase inhibitors and that it delays the deterioration of the cognitive dysfunction of mild Altzheimer's disease patients. Clinical Trial Registration: http://clinicaltrials.gov Japan Registry of clinical trials, identifier jRCTs 071190018.

Ribavirin concentration in the later stages of 48 week pegylated interferon-alpha2b plus ribavirin therapy for chronic hepatitis C is useful for predicting virological response.

OBJECTIVES: The current standard of care for chronic hepatitis C patients is a pegylated interferon-α plus ribavirin combination treatment. This study was carried out to determine the relationship between ribavirin concentration in the later stages of treatment and virological relapse. PATIENTS AND METHODS: Serum ribavirin concentration of 183 chronic hepatitis C patients (genotype 1) treated with pegylated interferon-α2b plus ribavirin for 48 weeks was prospectively measured by HPLC at weeks 4, 12, 24, 36 and 48. Patients with undetectable serum hepatitis C virus (HCV) RNA 24 weeks after the end of treatment were designated as having sustained virological response (SVR). Patients with undetectable HCV RNA during the treatment but with virological relapse after the end of treatment were designated relapse. RESULTS: The mean ribavirin concentration at each testing point of patients with SVR (1401, 1725, 1803, 1811 and 1901 ng/mL) was significantly higher than that of relapse patients (998, 704, 607, 643 and 654 ng/mL) at weeks 4, 12, 24, 36 and 48, respectively (all P < 0.001). Multivariate regression analysis for relapse extracted ribavirin concentration at week 36, but not cumulative ribavirin dosage. The cut-off value by receiver operating curve analysis for predicting a relapse was 1503 and 1562 ng/mL at weeks 36 and 48, respectively. CONCLUSIONS: Ribavirin concentration in the later stages of treatment is an important marker of viral relapse.

Abbott RealTime PCR assay is useful for evaluating virological response to antiviral treatment for chronic hepatitis C.

This study was done to evaluate the utility of the Abbott RealTime PCR assay (ART) for the monitoring of chronic hepatitis C patients. The serum samples of 183 patients infected with hepatitis C virus (HCV) genotype 1b who had completed a 48-week period of pegylated interferon (PEG-IFN) alpha-2b plus ribavirin treatment were prospectively analyzed. Serum HCV RNA levels were measured both by ART and by the Roche COBAS Amplicor Monitor test, version2.0 (CAM) at baseline and at weeks 4, 12, 24, 36, and 48 of treatment, and at 24 weeks after the end of treatment (EOT). A significant positive correlation of pretreatment HCV RNA levels was found between ART and CAM (r = 0.595, P < 0.0001). Of the 183 patients, 66 (36.0%) achieved a sustained virological response (SVR). The logarithmic decline of the HCV RNA level from the pretreatment level determined by ART in SVR patients was significantly higher than that in non-SVR patients at all time points tested. The logarithmic decline determined by CAM in SVR patients was significantly higher than that in non-SVR patients only at week 4, but there was no significant difference at other weeks. Of 124 patients who were HCV RNA-negative at EOT by ART, 58 (46.8%) had a relapse of viremia at 24 weeks after EOT, whereas 77 of 143 patients (53.8%) who were HCV RNA-negative at EOT by CAM had a relapse. The relapse rate was lower when determined by ART than by CAM, but not significantly so. ART is more useful than CAM for evaluating the virological response to antiviral treatment for chronic hepatitis C.

[A case of AIDS-associated Kaposi's sarcoma with systemic invasion].

Kaposi's sarocoma (KS) is a well-known complication of the acquired immunodeficiency syndrome (AIDS). A 23-year-old man with AIDS complicated by multiple KS seen in January 2008 for anorexia and 10 kg weight loss had a CD4 cell count of 7/microL and a serum HIV RNA level of 29,000 copies/mL. Computed tomography (CT) and endoscopy showed multiple KS lesions in both lungs, the duodenum, small intestine, colon, liver, and both kidneys but not of the skin. Despite the administration of pegylated liposomal doxorubicin (PLD) and highly active antiretroviral therapy, he died in disease progression, unable to complete PLD, KS-related respiratory failure.