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.

A Japanese Patient with Gaucher Disease Treated with the Oral Drug Eliglustat as Substrate Reducing Therapy.

Gaucher disease is a rare genetic disorder caused by the deficiency of acid ß-glucosidase to effectively catalyze the degradation of glucosylceramide to glucose and ceramide. We report here the case of a 31-year-old male Japanese patient with Gaucher disease who switched from enzyme replacement therapy (ERT) to substrate reducing therapy (SRT). Liver dysfunction was identified at a routine medical checkup, and the patient was referred to our hospital with "idiopathic liver disease." Clinical laboratory tests indicated thrombocytopenia and splenomegaly, which are characteristic symptoms of Gaucher disease. To definitively diagnose Gaucher disease, a bone marrow biopsy and acid ß-glucosidase activity measurement were conducted; the results supported a diagnosis of Gaucher disease. This case emphasizes that it is possible for periodic medical checkups in adults to lead to the diagnosis of rare genetic disorders. The patient underwent ERT treatment with imiglucerase for 5 years; the platelet count rapidly increased and the spleen size rapidly decreased, indicating a good response to the drug. However, the patient increasingly felt the burden of visiting the hospital for 2 h of infusion ERT every 2 weeks. Consequently, it was jointly decided that he should switch from ERT to SRT with an oral drug. This switch was successful with no deterioration of laboratory data. This case report is the first to describe a Japanese Gaucher disease patient treated with eliglustat for >2 years. We showed that SRT is a well-tolerated and effective option for the treatment of Gaucher disease.

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.

Efficacy and safety of double filtration plasmapheresis in combination with interferon therapy for chronic hepatitis C.

AIM: Efficacy and safety of double filtration plasmapheresis (DFPP) for chronic hepatitis C were prospectively analyzed in Japanese clinical settings. METHODS: All patients who received DFPP in combination with interferon (IFN) therapy for chronic hepatitis C were serially recruited at 36 institutions between April 2008 and July 2009 in Japan. RESULTS: A total of 239 patients were analyzed for the safety of DFPP and 206 patients for the efficacy. Of the 206 patients, 181 patients were treated with DFPP in combination with pegylated interferon plus ribavirin (PEG-IFN/RBV + DFPP). Among the 181 patients, 60 patients (33.1%) were treatment-naïves, 35 (19.3%) relapsers and 62 (34.3%) non-responders. Complete early virological response (cEVR) in patients treated with PEG-IFN/RBV + DFPP was achieved in 57.5% overall, 70.0% in treatment-naïves, 57.1% in relapsers and 41.9% in non-responders. In patients with previous PEG-IFN/RBV therapy, cEVR were found in 63.0% of relapsers and 18.9 % of non-responders, and cEVR in patients with other than PEG-IFN/RBV therapy as previous IFN therapy, relapsers and non-responders was 37.5% and 76.0%, respectively. Adverse events were found in 55 patients (23.0%). Serious adverse events were found in four patients (1.7%) who showed puncture-site injury. Adverse events were related to female sex, but not related to age, and DFPP could be performed safely. CONCLUSION: The cEVR results in this study suggest that high rates of sustained virological response can be achieved in retreated and treatment-naïve patients using DFPP in combination with PEG-IFN/RBV therapy. Results indicate that this therapy could be safely conducted, even in elderly patients.

Role of gastric distention with additional water in differentiating locally advanced gastric carcinomas from physiological uptake in the stomach on 18F-fluoro-2-deoxy-D-glucose PET.

PURPOSE: In this study, we investigated the role of gastric distention with additional water to determine whether it is beneficial for the differentiation of locally advanced gastric carcinomas from physiological 18F-fluoro-2-deoxy-D-glucose (FDG) uptake in the stomach and to characterize the FDG uptake of gastric carcinomas by relating it to the histopathological properties of the tumours. METHODS: Sixteen patients with locally advanced gastric carcinomas and 20 control patients were studied by FDG-PET. After whole-body PET imaging, the patients drank 400 ml of water and then spot imaging with additional water of the stomach was performed. The final diagnosis was determined from the results of surgery. The gastric areas were divided into the upper, middle, and lower parts. The degree of FDG uptake in the stomach was qualitatively evaluated by visual grading into three degrees. For quantitative analysis, the regional tumour uptake was measured by mean standardized uptake values using a region of interest technique. RESULTS: In visual analysis, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET without additional water ingestion were 100, 50, 62, 100 and 72%, respectively, and those of PET with additional water ingestion were 88, 100, 100, 91 and 94%, respectively. Using spot imaging under the condition with additional water ingestion, four gastric carcinomas were depicted more clearly. CONCLUSION: Gastric distention as a result of patients drinking a glass of water is a simple and noninvasive method for improving the diagnostic accuracy of FDG-PET in patients with locally advanced gastric carcinoma.