High serum growth differentiation factor 15 is a risk factor for the occurrence of hepatocellular carcinoma in chronic hepatitis B patients treated with nucleos(t)ide analogs.

Aim: Patients with chronic hepatitis B (CHB) remain at risk for hepatocellular carcinoma (HCC) even with nucleos(t)ide analog therapy. We evaluated risk factors for HCC development, including serum hepatitis B virus (HBV) RNA, hepatitis B core-related antigen level, and growth differentiation factor 15 (GDF15) level, a predictor of HCC development in patients with chronic hepatitis C.

Methods: We collected clinical data and stored serum from CHB patients without a history of HCC who were receiving nucleos(t)ide analog treatment for more than 1 year and whose HBV DNA level was less than 3.

Capsid Allosteric Modulators Enhance the Innate Immune Response in Hepatitis B Virus-Infected Hepatocytes During Interferon Administration.

Capsid allosteric modulators (CAMs) inhibit the encapsidation of hepatitis B virus (HBV) pregenomic RNA (pgRNA), which contains a pathogen-associated molecular pattern motif. However, the effect of CAMs on the innate immune response of HBV-infected hepatocytes remains unclear, and we examined this effect in this study. Administration of a CAM compound, BAY41-4109 (BAY41), to HBV-infected primary human hepatocytes (PHHs) did not change the total cytoplasmic pgRNA levels but significantly reduced intracapsid pgRNA levels, suggesting that BAY41 increased extracapsid pgRNA levels in the cytoplasm.

SIRT1 enhances hepatitis virus B transcription independent of hepatic autophagy.

Autophagy is an intracellular process that can lead to the degradation of malfunctioned proteins and damaged organelles to maintain homeostasis during cellular stress. Here, we evaluated the change in hepatitis B virus (HBV) production by regulating hepatic autophagy in HBV-producing cells. We examined focusing on a relation with a positive autophagy regulator, sirtuin1 (SIRT1).

Immunological responses against hepatitis B virus in human peripheral blood mononuclear cell-engrafted mice.

It is well known that immune-mediated virus elimination is necessary for the treatment of HBV infection. Reconstitution of human immune cells in liver chimeric mice is warranted to understand the immunopathogenesis of HBV infection. Here, we report a new immunologically humanized mouse model with a human immune system via reconstitution of immunodeficient NOG-Iaβ/β2 m double KO mice, which are NOG mice that are deficient in both MHC class I and II (DKO-NOG mice), with human HLA-A2-positive peripheral blood mononuclear cells (PBMCs).

Administration of low-dose epoetin-alpha facilitates adherence to ribavirin in triple therapy with pegylated interferon-alpha-2b and telaprevir.

Aim: Anemia frequently develops in patients given pegylated interferon, ribavirin (RBV), telaprevir (TVR) triple therapy and restricts treatment by forcing reduction or discontinuation of RBV administration. We investigated whether erythropoietin (EPO) could alleviate RBV-induced anemia to help maintain the RBV dose during the first 12 weeks, the triple therapy phase.

Methods: Twenty-two patients with hepatitis C virus (HCV) genotype 1 were enrolled.

Identification of egg-jelly substances triggering sperm acrosome reaction in the newt, Cynops pyrrhogaster.

Our previous studies have shown that the acrosome reaction (AR) occurs in egg-jelly of the Japanese newt, Cynops pyrrhogaster. This is analogous to the substances of echinoderms but distinct from those of many other vertebrates derived from the egg envelope or its derivative, the zona pellucida. To identify the AR-inducing substances in newt egg jelly, a monoclonal antibody (mAb) was generated against the jelly by screening the culture supernatants to find the one that best neutralized the AR-inducing activity of the jelly substance.

Numbers of people with HIV/AIDS reported and not reported to surveillance in Japan.

Background: Trends in the numbers of Japanese patients with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) reported to the HIV/AIDS surveillance system in Japan were examined. We attempted to estimate the cumulative number of Japanese with HIV, including people with HIV not reported to the surveillance.

Methods: Data from the HIV/AIDS surveillance in Japan up to the end of 2002 were available.

[A patient with gastric cancer with para-aortic lymph node metastases surviving for 9 years after effective preoperative chemotherapy and radical operation].

A 63-year-old male patient with type 3 advanced gastric cancer was referred to our hospital. Preoperative examination by CT-scan revealed swollen para-aortic lymph nodes and cancer invasion to the pancreas. The patient was treated pre-operatively with intravenous 5-FU, 500 mg/body/day, continuous infusion for 1 week.

Delays and continuation of hospital visits among HIV-infected persons and AIDS cases in Japan.

This study attempts to clarify the distribution patterns of delay between HIV transmission and the first hospital visit among HIV-infected persons and AIDS cases in Japan except those infected through blood products. Such hospital visit patterns were analyzed, and the rates of reporting for HIV/AIDS surveillance among diagnosed HIV-infected persons and AIDS cases in hospitals were shown. From 1991 to 1997, a survey and subsequent follow-up were conducted among HIV-infected persons and AIDS cases diagnosed at 74 hospitals in Tokyo.

Trends in HIV and AIDS based on HIV/AIDS surveillance data in Japan.

Background: In recent years a decline in the number of new AIDS cases has been observed in several industrialized countries. It is important to know whether these recent trends observed in North America and Europe are also occurring in Japan.

Methods: The number of people reported with HIV and AIDS by nationality, route of infection, and sex was calculated based on the HIV/AIDS surveillance data available in Japan through December 1997.

Summary of entire Japanese thorotrast follow-up study: updated 1998.

Updated data from two series in a cancer mortality study for a total of 412 Japanese Thorotrast patients were combined. The rate ratio for all deaths of Thorotrast patients, compared to controls, started to increase after a latent period of 20 years after injection of Thorotrast. Rate ratios for liver cancer, liver cirrhosis, leukemia and lung cancer were 35.

1998 results of the first series of follow-up studies on Japanese thorotrast patients and their relationships to an autopsy series.

The 1998 survey of the first series of epidemiological studies of Japanese Thorotrast patients revealed that 18 (6.9%) were alive and 244 (93.1%) had died among 262 war-wounded veterans to whom Thorotrast had been administered intravascularly.

Problems in the health management of persons with spinal cord injury.

This study was conducted to clarify the features of complications attending spinal cord injury (SCI). A comparison was made of the prevalence of disease among patients with SCI (SCIP) with that in the general population in Japan (National Livelihood Basic Survey). For this purpose, a survey was conducted on 244 males at 8 Rosai Rehabilitation Centers (Workman's Accident Compensation Rehabilitation Workshops).

Morbidity rates of complications in persons with spinal cord injury according to the site of injury and with special reference to hypertension.

It has been reported that since 1982 the incidence in persons with spinal cord injury (SCI) of hypertension is commoner than it is in the general population of the same age groups in Japan. In the current study, we examined outpatient morbidity rates and standardised outpatient morbidity ratios (SOMR) according to the site of injury, as well as blood pressure levels and history of disease, and compared the incidences with those for the general population. The subjects consisted of 195 men with SCI.

[Prediction of future trends of HIV infection and AIDS in Japan].

Current status and future trends of HIV infection and AIDS in Japan were estimated based on AIDS surveillance data up until 1992, excluding HIV infection from blood products and blood-borne transmission. The coverage rate of reports of HIV infection was estimated as the proportion of the reported AIDS cases who are also included in reports of HIV infection. Current numbers of HIV infected persons were then estimated to be the reported numbers divided by the coverage rate.

[Systems analytical investigation of the effect of countermeasures against the AIDS epidemic among homosexuals].

In Japan, the AIDS (Acquired Immunodeficiency Syndrome) epidemic among haemophiliacs has been the most urgent issue, because of the large number of haemophiliacs with AIDS. However, after governmental approval of the production of heated coagulating agents in 1985 and 1986, the prime object of prevention against the AIDS epidemic shifted from transmission through coagulation agents to that through sexual contacts. In order to investigate the most appropriate countermeasures against the AIDS epidemic among homosexuals in Japan, the numbers of HIV (Human Immunodeficiency Virus)-infected cases and AIDS cases in the future were estimated, and changes of the future numbers of HIV-infected persons and AIDS cases by behavior of homosexuals were compared using a systems analytical method.

[A method of interval estimation for number of patients in the nationwide epidemiological survey on intractable diseases].

A method for estimating the intervals for the number of patients with intractable diseases from nationwide epidemiological surveys was developed under the assumption that response is independent of frequency of patients. This method is based on data utilizing the number of response hospitals classified by their reported number of patients. The approximate 95% confidence intervals of numbers of several intractable diseases patients were estimated using this method.

[Relation of baseline examination results to death from ischemic heart disease, cerebro-vascular disease and sudden death].

The relation of variables obtained from a baseline examination to death from ischemic heart disease (IHD), cerebro-vascular disease (CVD) and sudden death (SUD) was analyzed in a case-control study. From questionnaire survey of approximately 180,000 subjects who underwent baseline health examinations in 1971-1986 at Aichi prefectural center of health care, 148 deaths were selected for this study. The number of cases on IHD, CVD and SUD was 36, 60, and 52, respectively.

[A note on methods for estimating the number of patients in the nationwide epidemiological survey on intractable diseases].

To find the most adequate method for estimating the number of patients in nationwide epidemiological surveys of intractable diseases, we examined six existing methods using reported data on 13 selected diseases. Estimated numbers of patients by the methods, except for methods with theoretical inadequacy or other problems, were almost equal to each other. The simple method, by which the number of patients is estimated as the reported one divided by the response rate, is recommended.