Background
HCV infection in chronic hemodialysis patients is high, has a poor prognosis and high risk of renal graft failure, and requires nosocomial infection control measures. However, options of ...anti-HCV therapy in such patients are limited and unsatisfactory. In this study, we report effectiveness and safety of HCV-NS5A-inhibitor daclatasvir (DCV) and protease-inhibitor asunaprevir (ASV) combination therapy for hemodialysis patients with HCV infection.
Methods
This study was registered at the UMIN Clinical Trials Registry as UMIN000016355. Thirty-four dialysis patients were treated with DCV/ASV combination therapy between January 2015 and November 2015. Of those, 21 patients who were followed more than 12 weeks after treatment ended were included. We evaluated the 12-week sustained virologic response (SVR12) and adverse events during treatment.
Results
Of the 21 patients, four had compensated liver cirrhosis and three had resistance-associated variant of NS5A (NS5A RAVs)-Y93H at baseline. Overall, total of 95.5 % (20/21) of the patients achieved SVR12. Of note, all patients with cirrhosis or NS5A RAVs achieved SVR12. One relapser patient at 4 weeks post-treatment had NS3 D168E RAVs at baseline. A total of 20 patients (95.5 %) completed the 24-week therapy. One patient discontinued treatment at week 12 due to ALT elevations and achieved SVR12.
Conclusions
DAV and ASV combination therapy for chronic hemodialysis patients with HCV infection was highly effective and well tolerated, even in elderly patients and patients with liver cirrhosis and NS5A-RAVs.
Backgrounds
The present study sought to establish a standard third-line eradication regimen for
Helicobacter pylori
in Japan.
Methods
Subjects were 204 patients with
H. pylori
infection in whom the ...standard Japanese first- and second-line eradication therapies had proven unsuccessful. Patients were randomly assigned to one of the following third-line eradication therapy groups: (1) LA group: lansoprazole (LPZ) 30 mg 4 times a day (qid) + amoxicillin (AMPC) 500 mg qid for two weeks; (2) LAL group: LPZ 30 mg twice a day (bid) + AMPC 750 mg bid + levofloxacin (LVFX) 300 mg bid for one week; (3) LAS group: LPZ 30 mg bid + AMPC 750 mg bid + sitafloxacin (STFX) 100 mg bid for one week. Patients for whom these therapies failed underwent a crossover fourth-line eradication regimen. Drug sensitivity was also tested for AMPC, clarithromycin (CAM), MNZ, LVFX, and STFX.
Results
Drug resistance rates prior to third-line eradication therapy were 86.4 % for CAM, 71.3 % for MNZ, 57.0 % for LVFX, 8.2 % for AMPC, and 7.7 % for STFX. Intention-to-treat analysis of third-line eradication therapy eradication rates showed a significantly higher rate in the LAS group (70.0 %) compared with the LA group (54.3 %;
p
< 0.05) and the LAL group (43.1 %;
p
< 0.001). The significantly lower rate in the LAL group than the LAS group was caused by bacterial resistance to LVFX.
Conclusions
The findings suggest that triple therapy with PPI, AMPC, and STFX for one week would be an effective standard third-line eradication regimen for
H. pylor
i in Japan.
Background
The Rome III diagnostic criteria had been used to diagnose functional gastrointestinal disorders (FGIDs) world wide, and functional bowel disorders (FBDs) including irritable bowel ...syndrome (IBS) have recently attracted the attention of Japanese physicians. However, there have been few reports on the prevalence of FBDs diagnosed by the Rome III diagnostic criteria.
Aims
The aim of this study was to determine the prevalence of FBDs diagnosed according to the diagnostic criteria of Rome III in Japan.
Patients and methods
All patients who were booked for colonoscopy were enrolled from eight institutions in Japan. This study was a prospective observational study in the period from April 2013 to December 2013. Patients filled out FGID questionnaires of Rome III when they were waiting for colonoscopy.
Results
Data for 1200 patients who underwent colonoscopy were analyzed. A total of 547 patients (45.6%) were diagnosed with FBDs. Out of those patients, 9.1% had IBS. According to the Rome III diagnostic criteria, 134 patients (11.2%) had functional bloating (FB), 73 (6.1%) had functional constipation (FC), 40 (3.3%) had functional diarrhea (FD), and 191 (15.9%) had unspecified functional bowel disorder (UFBD). Patients with FBDs had significantly higher rates of almost all symptoms (abdominal pain, hard or lumpy stools, loose or watery stools, and bloating) than those in the controls.
Conclusions
In Japan, the prevalence of FBDs and IBS is high, similar to that in the US. Many patients with FBDs have multiple symptoms.
Background
Hepatitis C virus (HCV) infection is common in hemodialysis patients and worsens their prognosis, while antiviral therapy options are limited. Recently, clinical trial and real-world, ...small-scale studies have reported excellent responses to direct-acting antivirals in patients with advanced chronic kidney diseases. However, real-world, large-scale data were lacking. This large multicenter analysis included HCV-infected hemodialysis patients receiving combination therapy with a nonstructural protein 5A (NS5A) inhibitor, daclatasvir (DCV), and a protease inhibitor, asunaprevir (ASV).
Methods
Twenty-three centers in Japan participated in this study of 123 hemodialysis patients with genotype 1 HCV infection, who received DCV/ASV combination therapy between November 2014 and March 2016. We collected and analyzed data relating to treatment outcome, baseline clinical information, laboratory measurements (during and after the treatment), and adverse events.
Results
Thirty-nine patients (31.7%) had advanced liver fibrosis, 12 (9.8%) had histories of hepatocellular carcinoma (HCC), and 18 (14.6%) had baseline resistance-associated variants (RAVs) of NS5A. The overall sustained virological response (SVR)12 rate was 95.9% (118/123). Notably, all patients with HCC and 94.4% (17/18) of those with NS5A RAVs achieved SVR12. Significant factors associated with non-SVR were advanced fibrosis and the interleukin-28B non-TT genotype at rs8099917. Four patients (3.3%) discontinued therapy because of adverse events including elevated serum alanine transaminase levels (
n
= 2), rash (
n
= 1), and HCC (
n
= 1); all of these achieved SVR12.
Conclusions
This real-world, nationwide study revealed that DCV/ASV combination therapy was safe and highly effective for hemodialysis patients with genotype 1 HCV infections. This study was registered at the UMIN Clinical Trials Registry (UMIN000024227).
Background
In recent years in Japan, the rate of clarithromycin (CAM) resistance in
Helicobacter pylori
has risen to around 30%, and the eradication rate with triple therapy proton pump ...inhibitor + amoxicillin (AMPC) + CAM has been trending downward to around 70%. In 2007, rabeprazole (RPZ)-based triple therapy (RPZ + AMPC + CAM: RAC therapy) was approved in Japan, and a large-scale nationwide study was therefore initiated to evaluate the efficacy and safety of RAC therapy in clinical practice.
Methods
Patients with
H. pylori
-positive gastric/duodenal ulcer (including ulcer scars) were administered triple therapy comprising RPZ 10 mg, AMPC 750 mg, and CAM 200 mg (or 400 mg), twice daily for 7 days.
Results
The eradication rate was 80.7% (2,551/3,162). The results of multivariate analysis indicated the following as factors affecting the eradication rate: sex, treatment compliance, history of
H. pylori
treatment, presence of urologic disease, presence of respiratory disease, and year of starting treatment. The incidence of adverse drug reactions (such as diarrhea and dysgeusia) was 4.4% (166/3,789). The results of multivariate analysis indicated the following as factors affecting the incidence of adverse drug reactions: sex, daily CAM dose, and history of allergies.
Conclusion
In a large-scale nationwide study of use in clinical practice, RAC therapy was confirmed to be effective and safe.
The purpose of this study is to compare the efficacy of a single administration of dexamethasone (DEX) on day 1 against DEX administration on days 1–3 in combination with palonosetron (PALO), a ...second‐generation 5‐HT3 receptor antagonist, for chemotherapy‐induced nausea and vomiting (CINV) in non‐anthracycline and cyclophosphamide (AC) moderately‐emetogenic chemotherapy (MEC). This phase III trial was conducted with a multi‐center, randomized, open‐label, non‐inferiority design. Patients who received non‐AC MEC as an initial chemotherapy were randomly assigned to either a group administered PALO (0.75 mg, i.v.) and DEX (9.9 mg, i.v.) prior to chemotherapy (study treatment group), or a group administered additional DEX (8 mg, i.v. or p.o.) on days 2–3 (control group). The primary endpoint was complete response (CR) rate. The CR rate difference was estimated by logistic regression with allocation factors as covariates. The non‐inferiority margin was set at −15% (study treatment group − control group). From April 2011 to March 2013, 305 patients who received non‐AC MEC were randomly allocated to one of two study groups. Overall, the CR rate was 66.2% in the study treatment group (N = 151) and 63.6% in the control group (N = 154). PALO plus DEX day 1 was non‐inferior to PALO plus DEX days 1–3 (difference, 2.5%; 95% confidence interval CI: −7.8%–12.8%; P‐value for non‐inferiority test = 0.0004). There were no differences between the two groups in terms of complete control rate (64.9 vs 61.7%) and total control rate (49.7% vs 47.4%). Anti‐emetic DEX administration on days 2–3 may be eliminated when used in combination with PALO in patients receiving non‐AC MEC.
In this study, we evaluated the efficacy of a single administration of dexamethasone (DEX) on day 1 against DEX administration on days 1–3 with palonosetron (PALO), for chemotherapy‐induced nausea and vomiting (CINV) in non‐AC (anthracycline and cyclophosphamide) moderately‐emetogenic chemotherapy (MEC) in the phase III study. Our randomized phase III study successfully demonstrated non‐inferiority of DEX administration only on day 1 compared to days 1–3 when used in combination with PALO during non‐AC MEC.
Background
Proton pump inhibitor (PPI) therapy, the first-line treatment for gastroesophageal reflux disease (GERD), is not always effective. This study aimed to examine the effect of pretreatment ...patient characteristics on response to PPI therapy.
Methods
Japanese outpatients with symptomatic GERD scheduled to receive endoscopy and PPI therapy were enrolled in this multicenter prospective observational study. The patients’ characteristics, including GERD and dyspeptic symptoms, anxiety, depression, and quality of life, were assessed using questionnaires before and 2 and 4 weeks after the start of PPI therapy. Factors affecting therapeutic response were examined by simple and multiple regression analyses using three patient-reported outcome measures as objective variables.
Results
Data from 182 patients were analyzed. In multiple regression analysis using the residual symptom rate as an objective variable, lower GERD symptom score (
p
< 0.05), absence of erosive esophagitis (
p
< 0.05), higher epigastric pain/burning symptom score (
p
< 0.05), and higher depression subscale score (
p
< 0.05) accompanied poorer therapeutic response. In analyses using the patient’s impression of therapy, lower GERD symptom score (
p
< 0.05) and absence of erosive esophagitis (
p
< 0.05) accompanied poorer therapeutic response. In analyses using the relative GERD symptom intensity evaluated using a numeric rating scale, lower GERD symptom score (
p
< 0.05), higher epigastric pain/burning symptom score (
p
< 0.1), and lower body mass index (
p
< 0.05) accompanied poorer therapeutic response.
Conclusions
Patients who complained of milder GERD symptoms before treatment were likely to have poorer response to PPI therapy. Association of absence of erosive esophagitis, severer epigastric pain/burning symptoms, lower body mass index, and severer depression with poorer therapeutic response was also suggested.
Aim
Telaprevir‐based therapy for chronic hepatitis C patients is effective; however, the high prevalence of dermatological reactions is an outstanding issue. The mechanism and characteristics of such ...adverse reactions are unclear; moreover, predictive factors remain unknown. Granulysin was recently reported to be upregulated in the blisters of patients with Stevens–Johnson syndrome (SJS). Therefore, we investigated the risk factors for severe telaprevir‐induced dermatological reactions as well as the association between serum granulysin levels and the severity of such reactions.
Methods
A total of 89 patients who received telaprevir‐based therapy and had complete clinical information were analyzed. We analyzed the associations between dermatological reactions and clinical factors. Next, we investigated the time‐dependent changes in serum granulysin levels in five and 14 patients with grade 3 and non‐grade 3 dermatological reactions, respectively.
Results
Of the 89 patients, 57 patients had dermatological reactions, including nine patients with grade 3. Univariate analysis revealed that grade 3 dermatological reactions were significantly associated with male sex. Moreover, serum granulysin levels were significantly associated with the severity of dermatological reactions. Three patients with grade 3 dermatological reaction had severe systemic manifestations including SJS, drug‐induced hypersensitivity syndrome, and systemic lymphoid swelling and high‐grade fever; all were hospitalized. Importantly, among the three patients, two patients' serum granulysin levels exceeded 8 ng/mL at onset and symptoms deteriorated within 6 days.
Conclusion
Male patients are at high risk for severe telaprevir‐induced dermatological reactions. Moreover, serum granulysin levels are significantly associated with the severity of dermatological reactions and may be a predictive factor in patients treated with telaprevir‐based therapy.
A seroepidemiologic study of the prevalence of Helicobacter pylori infection in Japan was performed, and the relationship between serum pepsinogen I and II levels (markers of gastritis and gastric ...atrophy) and H. pylori infection was investigated. Four hundred and eighteen asymptomatic children and adults were studied. The prevalence of anti-H. pylori immunoglobulin G antibody increased with age. For persons born after 1950, the frequency of H. pylori infection increased at approximately 1% per year; for those born before 1950 the prevalence was high (70%-80%) and relatively constant. Serum pepsinogen I and II levels were significantly higher in H. pylori-infected volunteers than in H. pylori-uninfected volunteers 51.6 +/- 3 vs. 42.9 +/- 2 ng/mL (P less than 0.05) for pepsinogen I; 16.0 +/- 1 vs. 7.5 +/- 0.8 ng/mL (P less than 0.001) for pepsinogen II. The ratio of pepsinogen I to pepsinogen II was significantly lower in H. pylori-infected volunteers (3.5 +/- 0.2) than in uninfected volunteers (6.3 +/- 0.3; P less than 0.001). The apparent decrease in prevalence of H. pylori accompanying the Westernization of Japan may eventually be accompanied by a reduction in the frequency of atrophic gastritis, the precursor lesion of the epidemic form of gastric carcinoma, and ultimately result in a decrease in the incidence of gastric carcinoma in Japan.
We describe a case of diffuse large B-cell lymphoma with massive portal vein tumor thrombosis in a patient with alcoholic cirrhosis. The tumor was detected only in the intrahepatic portal vein and ...the spermatic cord by FDG-PET/CT. Percutaneous liver biopsy and orchiectomy were performed and histological examination revealed diffuse large B-cell lymphoma. The tumor showed complete response after six courses of the combination chemotherapy. Portal vein tumor thrombosis of malignant lymphoma is extremely rare; moreover, it is possible that this is the first case of malignant lymphoma originating from the spermatic cord producing portal vein tumor thrombosis.
PDF
