灰旱獭感染HBV的临床和病理分析

目的 探讨灰旱獭感染HBV后临床表现、病理改变及其相关关系。方法 ①用含HBV DNA人血清对健康灰旱獭攻毒 ,依次传代 ,分析其临床血清学变化与病理改变的相关性。②用合成HBcAg多肽分别接种 :对HBcAb- 旱獭单用多肽Ⅰ、Ⅱ或多肽Ⅰ、Ⅱ与HBV DNA同时注射 :对HBcAb+ 旱獭注射多肽Ⅰ、Ⅱ。结果 ①攻毒与传代后临床反应的轻重与肝脏病理变化的程度一致。②HBcAg多肽具有核心蛋白疫苗的作用。可激发抗体的形成 ,阻断HBV的攻毒 ,使HBcAb转阴 ,与肝组织炎症反应一致。结论 肝组织炎变与血清变化密切相关 ,证实攻毒、传代结果可靠。多肽具有阻断、干预灰旱獭感染HBV的作用。

A comparative review of HLA associations with hepatitis Band C viral infections across global populations

Hepatitis B （HBV） and hepatitis C （HCV） viral infection or co-infection leads to risk of development of chronic infection, cirrhosis and hepatocellular carcinoma （HCC）. Immigration and globalization have added to the challenges of public health concerns regarding chronic HBV and HCV infections worldwide. The aim of this study is to review existing global literature across ethnic populations on HBV and HCV related human leukocyte antigen （HLA） associations in relation to susceptibility, viral persistence and treatment. Extensive literature search was conducted to explore the HLA associations in HBV and HCV infections reported across global populations over the past decade to understand the knowledge status, weaknesses and strengths of this information in different ethnic populations. HLA DR13 is consistently associated with HBV clearance globally. HLADRB1＊11/＊12 alleles and DQB1＊0301 are associated with HBV persistence but with HCV clearance worldwide. Consistent association of DRB1＊03 and ＊07 is observed with HCV susceptibility and non-responsiveness to HBV vaccination across the population. HLA DR13 is protective for vertical HBV and HCV transmission in Chinese and Italian neonates, but different alleles are associated with their susceptibility in these populations. HLA class I molecule interactions with Killer cell immunoglobulin like receptors （KIR） of natural killer （NK） cells modulate HCV infection outcome via regulating immune regulatory cells and molecules. HLA associations with HBV vaccination, interferon therapy in HBV and HCV, and with extra hepatic manifestations of viral hepatitis are also discussed. Systematic studies in compliance with global regulatory standards are required to identify the HLA specific viral epitope, stage specific T cell populations interacting with different HLA alleles during disease progression and viral clearance of chronic HBV or HCV infections among different ethnic populations. These studies would facilitate stage specific therapeutic strategies for clearance of HBV and HCV infections or co-infections across global populations and aid in identification of HBV-HCV combined vaccine. HLA associations of chronic HBV or HCV development with confounding host factors including alcohol, drug abuse, insulin resistance, age and gender are lacking and warrant detailed investigation across global populations.

Epigenetic changes in virus-associated human cancers

Epigenetics of human cancer becomes an area of emerging research direction due to a growing understanding ofspecific epigenetic pathways and rapid development of detection technologies. Aberrant promoter hypermethylation is aprevalent phenonmena in human cancers. Tumor suppressor genes are often hypermethylated due to the increasedactivity or deregulation of DNMTs. Increasing evidence also reveals that viral genes are one of the key players inregulating DNA methylation. In this review, we will focus on hypermethylation and tumor suppressor gene silencing andthe signal pathways that are involved, particularly in cancers closely associated with the hepatitis B virus, simian virus40 (SV40), and Epstein-Barr virus. In addition, we will discuss current technologies for genome-wide detection ofepigenetically regulated targets, which allow for systematic DNA hypermethylation analysis. The study of epigeneticchanges should provide a global view of gene profile in cancer, and epigenetic markers could be used for early detection,prognosis, and therapy of cancer.

Intramuscular vs intradermal route for hepatitis B booster vaccine in celiac children

AIM： To compare intradermal （ID） and intramuscular （IM） booster doses, which have been used in healthy and high risk subjects, such as healthcare workers, haemodialysis patients, human immunodeficiency virus patients, and renal transplant recipients unresponsive to initial hepatitis B vaccination, in celiac individuals. METHODS： We conducted our study on 58 celiac pa- tients, vaccinated in the first year of life, whose blood analysis had showed the absence of protective hepati- tis B virus （HBV） antibodies. All patients had received the last vaccine injection at least one year before study enrolment and they had been on a gluten free diet for at least 1 year. In all patients we randomly performed an HBV vaccine booster dose by ID or IM route. Thirty celiac patients were revaccinated with recombinant hepatitis B vaccine （Engerix B） 2 μg by the ID route, while 28 celiac patients were revaccinated with Engerix B 10 μg by the IM route. Four weeks after every boost- er dose, the anti-hepatitis B surface （HBs） antibody titer was measured by an enzyme-linked immune- adsorbent assay. We performed a maximum of three booster doses in patients with no anti-HBs antibodies after the first or the second vaccine dose. The cut off value for a negative anti-HBs antibody titer was 10 IU/L.Patients with values between 10 and 100 IU/L were considered ＂low responders＂ while patients with an antibody titer higher than 1000 IU/L were considered ＂high responders＂. RESULTS： No significant difference in age, gender, du- ration of illness, and years of gluten intake was found between the two groups. We found a high percent- age of ＂responders＂ after the first booster dose （ID = 76.7%, IM = 78.6%） and a greater increase after the third dose （ID = 90%, IM = 96.4%） of vaccine in both groups. Mloreover we found a significantly higher num- ber of high responders （with an anti-HBs antibody titer 〉 1000 IU/L） in the ID （40%） than in the IM （7.1%） group, and this difference was evident after the first booster dose of vaccination （P 〈 0.01）. No side effects were recorded in performing delivery of the vaccine by either the ID or IM route. CONCLUSION： Our study suggests that both ID and IM routes are effective and safe options to administer a booster dose of HBV vaccine in celiac patients. Howev- er the ID route seems to achieve a greater number of high responders and to have a better cost/benefit ratio.

DNA-guided hepatitis B treatment:Viral load is insufficient with few exceptions

In DNA-guided hepatitis B treatment, viral load is insufficient, and requires other viral markers for treatment of hepatitis B patients as in patients with acute exacerbation of chronic hepatitis B, end-stage renal disease on dialysis, human immunodeficiency virus co-infected patients. There are exceptions to this rule： a residual level hepatitis B virus （HBV） DNA at 24 wk predicts beneficial outcome and reduced resistance at i year. The genotypic viral resistance to antiviral agents and occult HBV infection can be determined by HBV-DNA levels.