Advances in immunomodulating therapy of HBV infection

Patients with chronic hepatitis B virus (HBV) infection have a higher risk of developing liver cirrhosis and hepatocellular carcinoma. Interferon-α, lamivudine and adefovir dipivoxil are the three approved treatment for chronic HBV infection and offers the only means of preventing the development of these complications. However, the efficacy of these agents, in terms of loss of Hepatitis B e antigen with or without seroconversion to Hepatitis B e antibody, normalization of serum alanine transaminase levels, loss of serum HBV DNA, and improvement in liver histology can only be achieved in 20-30% of those treated. Long-term treatment with either lamivudine or adefovir dipivoxil can result in the development of drug resistant mutants leading to an increased length of treatment with additional nucleoside analogues. These limitations of the current antiviral therapies underline the need for alternative therapies. Specific and nonspecific immunotherapeutic strategies to restore effective virus-specific T cell responses in those with chronic HBV infection offers an interesting alternative approach. These immunotherapeutic therapies include the adoptive transfer of HBV immunity, pegylated interferon and therapeutic vaccine therapies.published_or_final_versio

The natural history of chronic hepatitis B infection

Chronic hepatitis B infection is a global health problem that affects about 300 million people. Of these, 75% are Chinese. Most Chinese who become chronic carriers, contract the virus during the perinatal period. The natural history of these chronic hepatitis B carriers includes an initial immune tolerance phase, followed by immune clearance and an inactive hepatitis B non-replicative phase with the development of cirrhosis that may be complicated by hepatocellular carcinoma. The classification of hepato-cellular carcinoma has recently been revised. Based on immunohistochemical studies, it has been found that patients with hepatocellular carcinoma and biliary markers have a poorer survival than patients with hepatocellular carcinoma but who have negative biliary markers. Sometimes, a fourth phase, a hepatitis B envelope-negative hepatitis B virus replicative phase, reflecting the emergence of a pre-core mutant strain, may follow. Our improved understanding of the natural history of chronic hepatitis B infection has led to more effective approaches towards the control of this viral infection and its sequelae. Most importantly, immunisation against hepatitis B virus in the perinatal setting has been shown to prevent chronic infection.published_or_final_versio

PR interval prolongation in coronary patients or risk equivalent: excess risk of ischemic stroke and vascular pathophysiological insights

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Antithrombotic Therapy To Prevent Cognitive Decline In People With Small Vessel Disease On Neuroimaging But Without Dementia

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Predictive value of high-sensitivity troponin-I for future adverse cardiovascular outcome in stable patients with type 2 diabetes mellitus

INTRODUCTION: High-sensitivity cardiac troponin I(hs-TnI) and T levels(hs-TnT) are sensitive biomarkers of cardiomyocyte turnover or necrosis. Prior studies of the predictive role of hs-TnT in type 2 diabetes mellitus(T2DM) patients have yielded conflicting results. This study aimed to determine whether hs-TnI, which is detectable in a higher proportion of normal subjects than hsTnT, is associated with a major adverse cardiovascular event(MACE) in T2DM patients. METHODS AND RESULTS: We compared hs-TnI level in stored serum samples from 276 consecutive patients (mean age 65 +/- 10 years; 57% male) with T2DM with that of 115 age-and sex-matched controls. All T2DM patients were prospectively followed up for at least 4 years for incidence of MACE including heart failure(HF), myocardial infarction(MI) and cardiovascular mortality. At baseline, 274(99%) patients with T2DM had detectable hs-TnI, and 57(21%) had elevated hs-TnI (male: 8.5 ng/L, female: 7.6 ng/L, above the 99th percentile in healthy controls). A total of 43 MACE occurred: HF(n = 18), MI(n = 11) and cardiovascular mortality(n = 14). Kaplan-Meier analysis showed that an elevated hs-TnI was associated with MACE, HF, MI and cardiovascular mortality. Although multivariate analysis revealed that an elevated hs-TnI independently predicted MACE, it had limited sensitivity(62.7%) and positive predictive value(38.5%). Contrary to this, a normal hs-TnI level had an excellent negative predictive value(92.2%) for future MACE in patients with T2DM. CONCLUSION: The present study demonstrates that elevated hs-TnI in patients with T2DM is associated with increased MACE, HF, MI and cardiovascular mortality. Importantly, a normal hs-TnI level has an excellent negative predictive value for future adverse cardiovascular events during long-term follow-up.published_or_final_versio

Association of subclinical myocardial injury with arterial stiffness in patients with type 2 diabetes mellitus

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Orbital Ectopic Lymphoid Follicles with Germinal Centers in Aquaporin-4-IgG Positive Neuromyelitis Optica Spectrum Disorders

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Macrophage migration inhibitory factor expression in male and female ethanol-fed rats

Macrophage migration inhibitory factory (MIF) regulates macrophage accumulation at sites of injury and can promote the inflammatory response. We studied MIF expression in the intragastric feeding rat model for alcoholic liver injury. Male and age-matched female rats were fed ethanol or dextrose with fish oil. Two groups of male rats were fed medium-chain triglycerides with ethanol or dextrose. Analysis of liver histopathology, lipid peroxidation, endotoxin, mRNA, and immunohistochemistry for MIF, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were carried out. Male and female rats fed fish oil and ethanol showed necroinflammatory liver injury and had the highest expression of MIF, TNF-α, and IFN-γ in the liver. Decreased levels of MIF protein were seen in rats with higher endotoxin levels, suggesting that preformed MIF is released into the circulation. MIF is an important mediator of the inflammatory response in alcoholic liver disease and a potential therapeutic target.published_or_final_versio

Central nervous system inflammatory demyelinating disorders in Hong Kong Chinese

Poster PresentationBACKGROUND: Classical multiple sclerosis (CMS) must be differentiated from neuromyelitis optica (NMO) as treatments are different. Serum aquaporin-4 autoantibodies (AQP4 Ab) are specific for NMO spectrum disorders (NMOSD). We aimed to study the diagnoses of CNS inflammatory demyelinating disorder (IDD) patients presenting to a hospital over 29 years. METHODS: Chinese patients presenting with CNS IDD to our hospital from 1981 to 2009 were studied. Patients referred from other centres were excluded. Since 2008, patients had yearly magnetic resonance imaging (MRI) brain and cord for 3 years even without relap…published_or_final_versio

Tumor necrosis factor-α-induced protein 1 and immunity to hepatitis B virus

Aim: To compare the gene expression profile in a pair of HBV-infected twins. Methods: The gene expression profile was compared in a pair of H BV-infected twins. Results: The twins displayed different disease outco mes. One acquired natural immunity against HBV, whereas the other became a chronic HBV carrier. Eighty-eight and forty-six genes were found to be up- or downregulated in their PBMCs, respectively. Tumor necrosis factor-alpha-induced protein 1 (TNF-αIP1) that expressed at a higher level in the HBV-immune twins was identified and four pairs of siblings with HBV immunity by RT-PCR. However, upon HBV core antigen stimulation, TNF-αIP1 was downregulated in PBMCs from subjects with immunity, whereas it was slightly upregulated in HBV carriers. Bioinformatics analysis revealed a K+ channel tetramerization domain in TNF-αIP1 that shares a significant homology with some human, mouse, and C elegan proteins. Conclusion: TNF-αIP1 may play a role in the innate immunity against HBV. © 2005 The WJG Press and Elsevier Inc. All rights reserved.published_or_final_versio