The Real-World Safety and Efficacy of Daclatasvir and Asunaprevir for Elderly Patients

BACKGROUND/AIMS: Although daclatasvir with asunaprevir was approved in Japan for interferon ineligible or intolerant patients, patients aged ≥75 years were excluded in the phase III trial. The present study aimed to evaluate the safety and efficacy of this therapy for elderly patients aged ≥75 years and to clarify whether an extremely high sustained virological response (SVR) rate can be achieved, even in a real-world setting when patients with resistance-associated substitutions (RASs) to nonstructural protein 5A (NS5A) inhibitors or prior simeprevir failure are excluded. METHODS: Daclatasvir (60 mg) and asunaprevir (100 mg) were orally administered daily for 24 weeks. Patients without pre-existing NS5A RASs and simeprevir failure were enrolled in this study. RESULTS: Overall, 110 patients were treated. The median age was 73 years old. The SVR rates of total patients, those aged ≥75 years, and those aged < 75 years were 97% (107/110), 98% (46/47), and 97% (61/63), respectively. The treatment of two patients (2%) was discontinued because of adverse events. CONCLUSIONS: Daclatasvir with asunaprevir was a safe treatment, even in patients aged ≥75 years. When patients without pre-existing NS5A RASs and prior simeprevir failure were selected, an extremely high SVR rate could be achieved irrespective of age.

Simeprevir-Based Triple Therapy with Reduced Doses of Pegylated Interferon α-2a Plus Ribavirin for Interferon Ineligible Patients with Genotype 1b Hepatitis C Virus

BACKGROUND/AIMS: The present study aimed to evaluate the safety and efficacy of simeprevir-based triple therapy with reduced doses of pegylated interferon (PEG-IFN) and ribavirin for interferon (IFN) ineligible patients, such as elderly and/or cirrhotic patients, and to elucidate the factors contributing to a sustained virologic response (SVR). METHODS: One hundred IFN ineligible patients infected with genotype 1b hepatitis C virus (HCV) were treated. Simeprevir (100 mg) was given orally together with reduced doses of PEG-IFN-α 2a (90 μg), and ribavirin (200 mg less than the recommended dose). RESULTS: The patients’ median age was 70 years, and 70 patients were cirrhotic. Three patients (3%) discontinued treatment due to adverse events. The SVR rate was 64%. Factors that significantly contributed to the SVR included the γ-glutamyl transferase and α-fetoprotein levels, interleukin-28B (IL28B) polymorphism status, and the level and reduction of HCV RNA at weeks 2 and 4. The multivariate analysis showed that the IL28B polymorphism status was the only independent factor that predicted the SVR, with a positive predictive value of 77%. CONCLUSIONS: Simeprevir-based triple therapy with reduced doses of PEG-IFN and ribavirin was safe and effective for IFN ineligible patients infected with genotype 1b HCV. IL28B polymorphism status was a useful predictor of the SVR.

Low-Dose Pegylated Interferon α-2b Plus Ribavirin for Elderly and/or Cirrhotic Patients with Genotype 2 Hepatitis C Virus

BACKGROUND/AIMS: This study aimed to predict sustained viral response (SVR) to low-dose pegylated interferon (PEG-IFN) plus ribavirin of elderly and/or cirrhotic patients with genotype 2 hepatitis C virus (HCV) using viral response within 2 weeks. METHODS: Low-dose PEG-IFN-α-2b plus ribavirin was administered to 50 elderly and/or cirrhotic patients with genotype 2 HCV for 24 weeks. The dynamics of HCV RNA and HCV core antigen levels within 2 weeks were measured. RESULTS: The patients' median age was 66 years. There were 21 male and 29 female patients. The median baseline HCV RNA level was 5.7 log IU/mL. Rapid viral response was achieved in 17 patients (34%), SVR in 28 (56%), and two (4%) discontinued treatment. Univariate analysis of factors contributing to SVR showed significant differences for sex, baseline virus level, and response within 4 weeks. When 40 fmol/L was set as the cutoff value for the core antigen level at 1 week, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for predicting SVR were 93%, 75%, 84%, 88%, and 85%, respectively. CONCLUSIONS: Low-dose PEG-IFN plus ribavirin was a safe and cost-effective treatment for elderly and/or cirrhotic patients with genotype 2 HCV, and the viral response within 2 weeks was a useful predictor of SVR.

Prediction of a Null Response to Pegylated Interferon alpha-2b Plus Ribavirin in Patients with High Viral Load Genotype 1b Hepatitis C

BACKGROUND/AIMS: The present study aimed to clarify whether virological response within 2 weeks after therapy initiation can predict a null response to pegylated interferon alpha-2b plus ribavirin therapy in patients with high viral load genotype 1b hepatitis C. METHODS: The participants consisted of 72 patients with high viral load genotype 1b. The dynamics of viral load within 2 weeks were measured. RESULTS: Significant differences between null responders and nonnull responders were noted for interleukin (IL)-28B genotype, amino acid 70 substitution, alpha-fetoprotein, low-density lipoprotein cholesterol, hyaluronic acid, and viral response. The area under the curve (AUC) for the receiver operating characteristic curve of the hepatitis C virus (HCV) RNA level decline at 2 weeks (AUC=0.993) was the highest among the factors predicting the null response. When the cutoff value for the HCV RNA level decline at 2 weeks was set at 0.80 log, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in predicting a null response were 82%, 96%, 82%, 96%, and 94%, respectively. In comparison, values for the non-TT and mutant type of amino acid 70 substitution were similar to those for HCV RNA level decline at 2 weeks. CONCLUSIONS: Virological response at 2 weeks or the combination of IL-28B and amino acid 70 substitution are accurate predictors of a null response.

Clinical Practice of Integrative Medicine in the University / 日本補完代替医療学会誌

There is a traditional medicine that is Kampo, a kind of Chinese medicine, in Japan. Kampo medicine has been covered with Japanese health insurance since 1965 though it had been abolished in 1895. Recently, complementary and alternative medicine (CAM) imported from other countries, such as the chiropractic and the aromatherapy and so on, spreads out in Japan. The establishment of the academic meeting about CAM other than Kampo medicine is increasing. The institutions to bring it up though it is a small number as for CAM other than for Kampo medicine that is popularized widely on the education come out. However, there are few hospitals less than family doctors in terms of the practice of CAM. As a matter of fact, it is Japanese health insurance system to obstruct practicing integrative medicine in Japan. Kampo and part of acupuncture, moxibustion, Judo-seifuku like osteopathy and massage are covered with Japanese health insurance, but the others in CAM are not. After all, it is difficult to practice integrative medicine because Japanese law doesn't permit practicing CAM and western medicine at the same time under the health insurance system. The first practical institution of integrative medicine in Japanese university was established by Tokyo Women's Medical University in June, 2003. Patients can receive in the same day CAM at the Aoyama Institute of Women's and Natural Medicine and western medicine at Aoyama Hospital located on upper floor in the same building which is another institution attached with Tokyo Women's Medical University. The number of patients that visited our institution from June in 2003 to March in 2004 is 550 (Female: 171 men and 379 women), and an age was from 0 to 85 years old. We have a lot of patients suffering from cancer (80 men and 97 women). We also have patients who have a mental problem (18 men and 59 women) and patients of the incurable diseases by western medicine. CAM such as Kampo, acupuncture, moxibustion, Qigong, homeopathy, flower essence, aromatherapy, bodywork, minus ion treatment, phototherapy and the hyperthermia is performed with 2 doctors and a nurse who is bodyworker too. In the future, not only we will practice it but also research and education will be done, too.<br>

Complementary and Alternative Medicine in Dialysis Therapy / 全日本鍼灸学会雑誌

Dialysis therapy is the most common therapeutic modality in the treatment of end-stage renal failure. Over 200, 000 patients were maintained under dialysis therapy. An important goal in clinical nephrology is to control complications associated with long-term dialysis. Recently, complementary and alternative medicine (CAM) usehave increased dramatically in the world. This article demonstrates the efficacy of CAM including acupuncture for dialysis patients suffering from refractory complications.