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Nishi-Tokyo-shi, Japan

Al-Mahtab M.,Bangabandhu Sheikh Mujib Medical University | Akbar S.M.F.,Toshiba General Hospital | Aguilar J.C.,Center for Genetic Engineering and Biotechnology | Uddin M.H.,Clinical Research Organization | And 2 more authors.
Hepatology International

Purpose: The safety and clinical efficacy of a vaccine containing both hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) (HBsAg/HBcAg) were evaluated in patients with chronic hepatitis B (CHB). Methods: Eighteen patients with CHB were administered a vaccine containing 100 μg of HBsAg and 100 μg of HBcAg. The vaccine was administered ten times at 2-weekly intervals, the first five times via the nasal route only and the subsequent five times via both nasal and subcutaneous routes. The safety and efficacy of this therapeutic approach were assessed by periodic assessment of the patients' general condition, viral kinetics, and biochemical parameters during treatment and 24 and 48 weeks after therapy. The production of cytokines by peripheral blood mononuclear cells (PBMC) and antigen-pulsed dendritic cells (DC) was evaluated to assess the immunomodulatory effects of the HBsAg/HBcAg vaccine in CHB patients. Results: The HBsAg/HBcAg vaccine was safe in all patients. No flare of HBV DNA or alanine aminotransferase (ALT) was recorded in any patient. Sustained HBV DNA negativity and persistently normalized ALT were detected in 9 (50 %) and 18 (100 %) patients with CHB, respectively. PBMC and HBsAg/HBcAg-pulsed DCs from HBsAg/HBcAg-vaccinated CHB patients produced significantly higher levels of various cytokines [interleukin 1β (IL-1β), IL-6, IL-8, IL-12, and tumor necrosis factor α (TNF-α)] than those from control unvaccinated CHB patients (p < 0.05) after stimulation with HBsAg/HBcAg in vitro. Conclusion: HBsAg/HBcAg vaccine seems a safe and efficient therapeutic approach for patients with CHB. © 2013 Asian Pacific Association for the Study of the Liver. Source

Akbar S.M.F.,Toshiba General Hospital | Maumn A.M.,Bangabandhu Sheikh Mujib Medical University | Yoichi H.,Ehime University
Journal of Gastroenterology

Both optimism and frustration exist regarding therapy for patients with chronic hepatitis B virus infection. Due to the recent advent of several drugs with potent antiviral capacities and comparatively low rates of adverse effects, considerable optimism has developed regarding the treatment of these patients. Chronic hepatitis B is now a treatable disease, and suppression of hepatitis B virus replication, normalization of alanine aminotransferase levels, seronegativity/seroconversion of hepatitis B e antigen and hepatitis B surface antigen, and decreased hepatic inflammation and liver fibrosis have been documented in chronic hepatitis B virus-infected patients treated with antiviral therapy. In contrast, many frustrations regarding antiviral therapy for chronic hepatitis B have arisen, because the disease, although treatable, is not curable. The present regimens of antiviral therapy modulate some intermediate parameters or so-called surrogate markers in chronic hepatitis B virus-infected patients, but usually fail to improve all intermediate parameters or ultimate clinical outcomes. In addition, major concerns remain about the applicability and use of antiviral drugs in developing and resource-constrained countries in which healthcare delivery systems do not support the proper use of antiviral therapy. New and more effective therapeutic regimens for chronic hepatitis B patients are needed that take into account potential surrogate markers of treatment outcomes and allow for effective collaboration between resource-constrained and advanced countries. Source

Akbar S.M.F.,Toshiba General Hospital | Al-Mahtab M.,Bangabandhu Sheikh Mujib Medical University | Uddin M.H.,Clinical Research Organization | Khan M.S.I.,Ehime University
Hepatobiliary and Pancreatic Diseases International

BACKGROUND: As the host immunity is diminished in patients with chronic hepatitis B (CHB), different approaches have been used to up-regulate their immune responses to produce therapeutic effects. But, cytokines, growth factors and polyclonal immune modulators could not exhibit sufficient therapeutic effects in these patients. Immune therapy with HBV-related antigens (vaccine therapy) has been used in CHB patients. But there is a paucity of information about the design of HBV antigen-based immune therapy in these patients. DATA SOURCE: Preclinical and clinical studies on immune therapy with HBsAg-based vaccine, HBcAg and combination of HBsAg/HBcAg-based vaccines have been discussed. RESULTS: HBsAg-based prophylactic vaccine was used as an immune therapeutic agent in CHB patients; however, monotherapy with HBsAg-based immune therapy could not lead to sustained control of HBV replication and/or liver damages. HBsAg-based vaccine was used as a combination therapy with cytokines, growth factors, and antiviral drugs. HBsAg-based vaccine was also used for cell-based therapy. However, satisfactory therapeutic effects of HBsAg-based vaccine could not be documented in CHB patients. In the mean time, evidences have supported that HBcAg-specific immunity is endowed with antiviral and liver protecting capacities in CHB patients. Recent data concentrate on the clinical use of combined HBsAg- and HBcAg-based vaccines in CHB patients. CONCLUSION: Antigen-based immune therapy with HBV-related antigens may be an alternative method for the treatment of CHB patients but proper designs of antigens, types of adjuvants, dose of vaccinations, and routes of administration need further analyses for the development of an effective regimen of immune therapy against HBV. © 2013, Hepatobiliary Pancreat Dis Int. All rights reserved. Source

Fazle Akbar S.M.,Toshiba General Hospital | Al-Mahtab M.,Bangabandhu Sheikh Mujib Medical University | Hiasa Y.,Ehime University
Journal of Clinical and Experimental Hepatology

Presently-available antiviral drugs may not be a satisfactory option for treatment of patients with chronic hepatitis B (CHB). In spite of presence of several antiviral drugs, sustained off-treatment clinical responses are not common in CHB patients treated with antiviral drugs. In addition, antiviral drug treatment may have limited effects on blocking the progression of HBV-related complications. However, substantial long-term risk of viral resistance and drug toxicity are related with maintenance antiviral therapy in CHB patients with presently-available antiviral agents. The infinite treatments with antiviral drugs for CHB patients are also costly and may be unbearable by most patients of developing and resource-constrained countries. In this situation, there is pressing need to develop new and innovative therapeutic approaches for patients with chronic hepatitis B virus (HBV) infection. Immune therapy has emerged as an alternate therapeutic approach for CHB patients because studies have shown that host immunity is either impaired or derailed or distorted or diminished in CHB patients compared to patients with acute resolved hepatitis B who contain the HBV replication and control liver damages. Both non antigen-specific immune modulators and HBV antigen-specific agents have been used in CHB patients during last three decades. However, similar to antiviral therapy, the ongoing regimens of immune therapeutic approaches have also been unable to show real promises for treating CHB patients. The concept of immune therapy for treating CHB patients seems to be rationale and scientific, however, concerns remain about suitable designs of immune therapy for CHB patients. © 2014 INASL. Source

Imai K.,Toshiba General Hospital
Recent Patents on Endocrine, Metabolic and Immune Drug Discovery

Osteoporosis is a major public health problem affecting all countries and giving rise to fractures. The World Health Organization (WHO) published a set of diagnostic criteria to define osteoporosis in postmenopausal Caucasian women, using bone mineral density (BMD) values measured by dual energy X-ray absorptiometry (DXA). Currently, measurement of BMD by DXA (g/cm2) has been the standard method for diagnosing osteoporosis, in addition to assessing fracture risk and therapeutic effects. Quantitative computed tomography (QCT) can quantify volumetric BMD (mg/cm3), and cancellous bone can be measured independently of surrounding cortical bone and aortic calcification. Recently, quantitative ultrasound (QUS) is emerging as a relatively low-cost and readily accessible alternative means to identify osteoporosis and evaluate fracture risk. More recently, finite element (FE) method based on data from computed tomography (CT) has been used to assess bone strength, fracture risk, and therapeutic effects on osteoporosis. In this review, recent patents and methods for assessing bone mineral density, bone strength, fracture risk and therapeutic effects on osteoporosis are outlined. © 2010 Bentham Science Publishers Ltd. Source

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