鸡源类人乙肝病毒与人乙肝病毒S基因序列分析

为揭示动物乙肝病毒与人乙肝病毒之间的相关性研究打下基础，以人乙肝病毒Ｓ基因两侧的保守区域作为模板，采用套式ＰＣＲ方法，成功地扩增出鸡源类人乙肝病毒部分基因（１．２ｋｂ）。序列分析结果表明，鸡源类人乙肝病毒与人乙肝病毒Ｓ基因似有一定的同源性，但在保守区域（Ｓ区）内存在较大的核苷酸序列差异。

在淮南地区奶牛牛奶中发现类人乙肝病毒

近年来,我们用人的乙型肝炎标志物试剂检查了48头奶牛的牛奶,并选择4份标本作免疫电镜。结果矿务局23号、8629号奶牛的牛奶HBsAg(+);7826号和6-8238号奶牛的牛奶HBsAg(-)。免疫电镜在矿务局23号和8629号标本中查到了病毒颗粒。其中大球形颗粒直径35～45nm;小球形颗粒直径18～20nm,类似于HBV的Dane和HBsAg颗粒;较小型颗粒直径10～15nm,其本质有待于进一步研究。

Hepatocellular carcinoma,human immunodeficiency virus and viral hepatitis in the HAART era

The incidence of hepatocellular carcinoma(HCC)in patients with human immunodeficiency virus(HIV) is rising.HCC in HIV almost invariably occurs in the context of hepatitis C virus(HCV)or hepatitis B virus (HBV)co-infection and,on account of shared modes of transmission,this occurs in more than 33% and 10% of patients with HIV worldwide respectively.It has yet to be clearly established whether HIV directly accelerates HCC pathogenesis or whether the rising incidence is an epiphenomenon of the highly active antiretroviral therapy(HAART)era,wherein the increased longevity of patients with HIV allows long-term complications of viral hepatitis and cirrhosis to develop.Answering this question will have implications for HCC surveillance and the timing of HCV/HBV therapy,which in HIV co-infection presents unique challenges.Once HCC develops,there is growing evidence that HIV co-infection should not preclude conventional therapeutic strategies,including liver transplantation.

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.

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.

Tenofovir induced severe thrombocytopenia

Tenofovir disoproxil fumarate is used in the management of hepatitis B and human immunodeficiency virus infection.We present a 50 years old lady,post liver transplant,who was switched over from entecavir to tenofovir,for management of hepatitis B reactivation.She developed bleeding diathesis and severe thrombocytopenia was detected on investigations.Bone marrow examination showed normocellular marrow with megakaryocytes.Tenofovir was stopped and she was started on intravenous immunoglobulin,followed by steroids.There was improvement in platlet counts.The case highlights a rare side effect of tenofovir therapy.

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.