Efficacy and safety of glecaprevir and pibrentasvir in Japanese patients with hepatitis C virus infection aged 75 years or older.

BACKGROUND: It is estimated that approximately 50% of patients with hepatitis C virus (HCV) infection in Japan are currently over 75 years old. However, patients aged ≥ 75 years are typically underrepresented in clinical trials of direct-acting antivirals. This study aimed to evaluate the efficacy and safety of glecaprevir and pibrentasvir (G/P) treatment in Japanese patients with HCV infection aged ≥ 75 years. METHODS: This multicenter, retrospective study included 271 Japanese patients with HCV infection from 12 centers in Miyazaki Prefecture, Japan. Demographic, clinical, virological, and adverse events (AEs) data obtained during and after G/P treatment were collected from medical records. The patients were divided into two groups: younger (n = 199, aged < 75 years) and older (n = 72, aged ≥ 75 years). Virological data and AEs were analyzed according to the age group. RESULTS: In intention-to-treat (ITT) and per-protocol analyses, the overall sustained virological response 12 (SVR12) rates were 93% and 98.8%, respectively. Two patients in the older group and 14 patients in the younger group dropped out before SVR12 assessment. Although patients in the older group tended to have liver cirrhosis, 95.8% in the older group and 92% in the younger group achieved SVR12 in the ITT analysis (P = 0.404). In total, 48 (17.7%) patients experienced treatment-related AEs. Common AEs during treatment included pruritus, headache, and fatigue. The AEs were not significantly different between the two groups. CONCLUSIONS: Compared with younger patients, older patients showed similar virological response and tolerance to G/P treatment.

Frailty Status Predicts New Long-term Care Insurance Certification in Hepatitis C Patients Receiving Antiviral Therapy.

BACKGROUND/AIM: Direct-acting antiviral (DAA) therapies for patients with hepatitis C virus (HCV) infection deliver higher cure rates and lower frequencies of adverse events than existing therapies, though DAA treatment costs $45,000-64,000 in Japan. The prognosis of patients who require new long-term care insurance (LTCI) certification is inferior to that of patients who do not. Here, we clarify the factors associated with new LTCI certification in elderly patients with HCV infection who undergo DAA therapy. PATIENTS AND METHODS: We retrospectively surveyed 53 patients aged ≥70 years who were treated with DAAs, and evaluated the factors associated with new LTCI certification. RESULTS: Of 53 patients, 10 required new LTCI certification. Age ≥85 years and a modified Japanese Cardiovascular Health Study index ≥2 were independently associated with new LTCI certification. CONCLUSION: In elderly HCV patients, poor frailty status strongly predicted new LTCI certification after DAA therapy.

Efficacy and safety of sofosbuvir and ledipasvir in Japanese patients aged 75 years or over with hepatitis C genotype 1.

AIM: To evaluate the efficacy and safety of a regimen containing sofosbuvir (SOF) and ledipasvir (LDV) in Japanese patients aged ≥ 75 years with hepatitis C genotype 1. METHODS: This multicenter, retrospective study consisted of 246 Japanese patients with HCV genotype 1 at nine centers in Miyazaki prefecture in Japan. Demographic, clinical, virological, and adverse effects (AE)-related data obtained during and after SOF/LDV therapy were collected from medical records. These patients were divided into two groups, younger (aged < 75 years) and elderly (aged ≥ 75 years). Virological data and AEs were analyzed by age group. RESULTS: The sustained virological response (SVR) rates at 12 wk after treatment were 99.2%, 99.4%, and 98.7% in the overall population and in patients aged < 75 and ≥ 75 years, respectively. Common AEs during therapy were headache, pruritus, constipation, and insomnia. These occurred in fewer than 10% of patients, and their incidence was not significantly different between the younger and elderly groups. Two patients discontinued treatment, one due to a skin eruption and the other due to cerebral bleeding. CONCLUSION: Compared with younger patients, elderly patients had a similar virological response and tolerance to SOF/LDV therapy.

[Two cases of acute hepatitis E infected with descendant strains of hepatitis E virus genotype 3 strain isolated from swine herd in Miyazaki Prefecture 12 years ago - one case had acute facial paralysis].

We experienced two cases of acute hepatitis E in Miyazaki Prefecture in the same period. The patients were unknown to each other and did not have any clear causes or common risk factors of hepatitis E virus (HEV) infection. Nucleotide sequences of the HEV isolates revealed that the two isolates were closely related but with different HEV genotype 3 strains. The two cases appeared to be infected from unknown and different sources. Molecular phylogenetic analysis indicated that the strains were probably descendants of the strains which had been isolated from swine herd in Miyazaki Prefecture 12 years previously. This result indicates that the strains persisted in pig farms, in wild life, or in the natural environment in this region. The source should be identified, and efforts should be made to prevent of the spread of the infection. One of the cases had acute facial paralysis, which might be an extra-hepatic manifestation of HEV infection.

Evaluation of gene, protein and neurotrophin expression in the brain of mice exposed to space environment for 91 days.

Effects of 3-month exposure to microgravity environment on the expression of genes and proteins in mouse brain were studied. Moreover, responses of neurobiological parameters, nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF), were also evaluated in the cerebellum, hippocampus, cortex, and adrenal glands. Spaceflight-related changes in gene and protein expression were observed. Biological processes of the up-regulated genes were related to the immune response, metabolic process, and/or inflammatory response. Changes of cellular components involving in microsome and vesicular fraction were also noted. Molecular function categories were related to various enzyme activities. The biological processes in the down-regulated genes were related to various metabolic and catabolic processes. Cellular components were related to cytoplasm and mitochondrion. The down-regulated molecular functions were related to catalytic and oxidoreductase activities. Up-regulation of 28 proteins was seen following spaceflight vs. those in ground control. These proteins were related to mitochondrial metabolism, synthesis and hydrolysis of ATP, calcium/calmodulin metabolism, nervous system, and transport of proteins and/or amino acids. Down-regulated proteins were related to mitochondrial metabolism. Expression of NGF in hippocampus, cortex, and adrenal gland of wild type animal tended to decrease following spaceflight. As for pleiotrophin transgenic mice, spaceflight-related reduction of NGF occurred only in adrenal gland. Consistent trends between various portions of brain and adrenal gland were not observed in the responses of BDNF to spaceflight. Although exposure to real microgravity influenced the expression of a number of genes and proteins in the brain that have been shown to be involved in a wide spectrum of biological function, it is still unclear how the functional properties of brain were influenced by 3-month exposure to microgravity.

Development and verification of hardware for life science experiments in the Japanese Experiment Module "Kibo" on the International Space Station.

Japan Aerospace Exploration Agency (JAXA) has developed a cell biology experiment facility (CBEF) and a clean bench (CB) as a common hardware in which life science experiments in the Japanese Experiment Module (JEM known as "Kibo") of the International Space Station (ISS) can be performed. The CBEF, a CO2 incubator with a turntable that provides variable gravity levels, is the basic hardware required to carry out the biological experiments using microorganisms, cells, tissues, small animals, plants, etc. The CB provides a closed aseptic operation area for life science and biotechnology experiments in Kibo. A phase contrast and fluorescence microscope is installed inside CB. The biological experiment units (BEU) are designed to run individual experiments using the CBEF and the CB. A plant experiment unit (PEU) and two cell experiment units (CEU type1 and type2) for the BEU have been developed.

Developmental status of Aquatic Animal Experiment Facility, Aquatic Habitat (AQH), for International Space Station.

Mitsubishi Heavy Industries (MHI) and Japan Aerospace Exploration Agency (JAXA) have been studying Aquatic Animal Experiment Facility, Aquatic Habitat (AQH), for International Space Station (ISS). The AQH will have the capabilities to accommodate small freshwater fish and amphibian for maximum 90 days on orbit. Three-generations of small freshwater fish (medaka and zebrafish), and egg through metamorphosis of amphibian (African clawed toad) could be experimented by AQH. Various experimental functions such as automatic feeding, air-water interface, day/night cycle, video observation, and specimen sampling mechanism will be also equipped in AQH. The water circulation system was improved from the past aquatic facilities for Space Shuttle experiments under the consideration of the long life-time, and a brand-new specimen chamber was developed to equip the above various experimental functions. Currently the prototype model of water circulation system and specimen chambers have been manufactured and biological compatibility tests are being conducted with medaka. The current developmental status of AQH is summarized.