乙型肝炎病毒突变与隐匿性感染的相关性

隐匿性HBV感染(OBI)指在机体肝组织中存在HBV DNA,血清HBsAg阴性,伴或不伴有血清HBV DNA阳性的感染状态.OBI与隐源性肝硬化和肝细胞癌有关,是输血、器官移植播散HBV的潜在危险因素,也是目前疫苗接种失败的主要原因之一.OBI的形成与多种机制有关,其中病毒突变是重要因素.此文就HBV基因不同区域突变与OBI感染的关系作一综述.     

隐匿性乙型肝炎病毒感染的流行病学研究进展

HBV感染是指血清中HBsAg和HBV DNA检测阳性.然而随着高灵敏分子生物学技术在HBV检测中的应用,发现部分HBV感染者血清HBsAg阴性,但血清或肝组织HBVDNA持续存在,从而提出隐匿性HBV感染(occult hepatitisB virus infection,OBI)的概念^[1].HBsAg阴性的HBV感染与许多临床情况有关,由于HBsAg阴性HBV感染难以用常规方法检出,成为较复杂的流行病学和临床问题^[2].目前OBI的流行病学研究主要集中于OBI在不同人群患病率的横断面调查,由于选取研究对象的方法不-,检测指标及方法各异,造成结果差别很大.本文就近年来OBI的流行病学调查方法、发病情况等研究进展进行综述.     

隐匿性乙型肝炎病毒感染的研究进展

隐匿性乙型肝炎病毒感染（occult HBV infection, OBI）是公共健康的一大难题,也是全球临床医学面临的挑战。由于目前检测方法以及临床实际问题的限制,不同研究中对于OBI的定义也不同。OBI的存在会影响临床诊断和输血安全,且OBI在临床高危人群中有再激活的风险,可能会导致肝硬化、肝癌和肝衰竭等终末期肝病。本文就近年OBI定义和不同人群流行率、OBI发生机制以及临床意义等研究进展进行综述。     

住院孕妇显性和隐匿性HBV感染及分子进化特征分析

目的了解住院孕妇显性和隐匿性乙型肝炎病毒感染(OBI)及其病毒株S基因分子进化特征。方法采用以医院为基础的住院孕妇队列研究,招募2012年6月1日—2013年3月15日医院产科孕妇1 130人,收集人口学资料和血清,并采用罗氏电化学发光法检测乙型肝炎病毒表面抗原(HBsA g)及巢式PCR进行HBV S片段的扩增并测序,分析并比较住院孕妇显性乙型肝炎病毒(HBV)感染与OBI的人口学分布特征及S区序列变异。结果在1 130名孕妇中,HBV感染比例为16.55%,其中显性HBV感染和OBI的比例分别为8.4%和8.1%。共获得136株HBV S基因序列,其中基因C型17株,基因B型119株。与基因B型显性HBV株相比,OBI株出现更高的核苷酸和氨基酸替换率,8个核苷酸位点出现统计学显著的次要等位基因频率,并导致HBV S基因和对应的HBV P基因出现非同义氨基酸替换,分别为5个(G44E、T126A、R129Q、W156L和Y200F)和4个(I438L、K478N/D、N481S/D和L511F)。此外,3例OBI出现W35终止码替换,1例OBI出现第123位和第124位点的插入替换。结论住院孕妇存在较高的HBV感染比例,OBI与显性HBV感染比例大致相当;B基因型OBI株出现统计显著的核苷酸和/或氨基酸位点替换,可能与OBI的发病机制有关。     

乙肝母婴传播类型与乙肝疫苗免疫效果的关系

持续性乙型肝炎病毒(hepatitis B virus,HBV)感染分为两类:乙型肝炎表面抗原(hepatitis B surface antigen,HBsAg)阳性(显性HBV感染)和阴性(隐匿性HBV感染,occult hepatitis B infection,OBI)。对显性感染的认识相对清楚,但对OBI的认识仍然有限。本文重点介绍OBI的危害及其流行情况,并分别阐述了母婴不同乙肝传播类型与乙肝疫苗免疫效果的关系。HBV以母婴传播为主,两类HBV感染在母婴传播上表现为四种类型:(Ⅰ)母亲HBV显性-子代HBV显性;(Ⅱ)母亲HBV显性-子代OBI;(Ⅲ)母亲OBI-子代OBI;(Ⅳ)母亲OBI-子代HBV显性。HBV疫苗免疫后时代可能以Ⅱ型传播为主。应加强对OBI的研究,重新评估现有HBV免疫策略对HBV母婴传播的影响。     

隐匿性乙型肝炎病毒感染研究进展

隐匿性HBV感染（OBI）已成为世界性公共卫生问题之一,严重影响乙型肝炎的临床诊断并威胁到输血安全。本文分析近年来关于OBI的概念、致病机制、在健康人群和不同患者中的流行率以及传播可能性方面的研究数据,结果显示OBI在健康人群及不同患者中均存在一定的流行率,并可能通过输血等途径传播,应引起重视。     

长沙地区无偿献血人群隐匿性乙型肝炎病毒感染情况分析

目的 了解长沙地区无偿献血人群隐匿性乙型肝炎病毒感染(occult hepatitis B virus infection,OBI)流行情况,探讨HBV基因型分布特征和S区氨基酸突变的情况。方法 对长沙地区检测结果为HBsAg-/HBV DNA+的无偿献血血液样本进行HBV血清标志物检测,对其中的OBI样本进行HBV病毒载量检测和S区基因扩增,分析血清学标志物抗HBs与病毒载量检出与否的关系,并对扩增产物进行HBV基因分型和突变位点分析。结果 2019年1月—2020年1月长沙地区173 893份无偿献血标本共确认58例OBI样本,OBI流行率为0.033%;共发现7种血清学模式,抗HBc单独阳性最多,占38.98%,所有样本中抗HBc阳性率为89.83%;16例样本能检测出病毒载量,其中14例样本浓度小于100 IU/ml;抗HBs阳性组和阴性组间的病毒载量检出率无统计学差异;75.0%(12/16)样本扩增出S区序列,基因型均为B型,均发生突变,其中11例的HBsAg抗原决定簇及周边主要亲水区域(major hydrophilic region, MHR)发生氨基酸突变。结论 长沙地区无偿献血者中的OBI感染率在全国属于偏低水平;HBV基因型主要是B型,MHR区的氨基酸突变可能是造成OBI的原因,突变有本地特点。     

多种肝脏疾病中隐匿性HBV感染检出率及其S基因MHR免疫逃逸相关突变特点分析

目的　分析多种肝脏疾病中隐匿性HBV感染（occult HBV infection, OBI）检出率,并探讨OBI患者HBV S基因主要亲水区（major hydrophilic region, MHR）免疫逃逸相关突变特点。方法　回顾性分析2005年1月—2017年12月就诊于中国人民解放军总医院第五医学中心的91 037例HBV感染住院患者临床资料,筛选出OBI患者并扩增其HBV S基因序列,分析其HBV S基因MHR免疫逃逸相关突变特点。结果　91 037例住院患者中OBI总检出率为0.53%（487/91 037）,急性乙型肝炎患者中OBI检出率最高（9.26%,130/1404）,肝硬化患者中OBI检出率最低（0.26%,78/29 921）。62例OBI患者组与124例非OBI患者组相比,OBI患者组MHR免疫逃逸相关突变总体检出率显著高于非OBI患者组（59.68% vs. 35.48%;P＜0.05）;OBI患者组MHR多个免疫逃逸相关突变的联合检出率显著高于非OBI患者组（43.55% vs. 22.58%;P＜0.05）;其中,sT118K、sK122R和sV168A 3种单点突变的检出率显著高于非OBI患者组。结论　本研究显示临床HBV感染患者中有较高的OBI检出率,而且不同肝脏疾病中OBI检出率不同。此外,HBV S基因MHR的免疫逃逸相关突变与临床实践中OBI的发生密切相关。     

孕妇显性或隐匿性乙型肝炎病毒感染肝功能指标比较研究

目的探讨妊娠合并显性乙型肝炎病毒(hepatitis B virus,HBV)或隐匿性乙型肝炎病毒感染(occult hepatitis B virus infection,OBI)对孕妇肝功能指标的影响。方法采用以医院为基础的住院孕妇队列研究。以活产分娩且肝功能检查资料完善的2 195例孕妇为研究对象,收集其临产前血清,检测乙型肝炎病毒表面抗原(hepatitis B virus surface antigens,HBs Ag)和HBV S/pre S/C片段,分析并比较显性HBV感染、OBI与非HBV感染孕妇的肝功能指标的差异。结果显性HBV感染孕妇的ALT、TBAS水平显著高于非HBV感染孕妇,而TP和ALB则明显降低,GLB在3组孕妇中总体差异有统计学意义(P0.05),AST、ALP、GGT、TBIL、DBIL在3组孕妇中总体差异无统计学意义(P0.05)。结论显性HBV感染的活产孕妇妊娠期间ALT、TBAS、TP、ALB指标值异于非HBV感染活产孕妇,未发现OBI活产孕妇肝功能指标与显性HBV、非HBV感染活产孕妇的差异。提示临床应加强对显性HBV感染孕妇的肝功能监测,减少不良妊娠结局发生,促进母婴健康。     

国际隐匿性乙型肝炎病毒感染(OBI)暨血液安全研讨会会议通知

<正>为促进我国输血医学的发展,由南方医科大学和广州血液中心共同承办的"国际隐匿性乙型肝炎病毒感染(OBI)暨血液安全研讨会"将于2014年10月9¹2日在广州南方医科大学召开。此次会议是亚太地区首次举办关于隐匿性乙型肝炎病毒感染(OBI)专题的国际性学术交流会议,同时开设中国区血液安全会议专场,届时将邀请该领域内国际知名专家、教授作主题报告。同时,参加本次研讨会的人员,针对OBI与血液安全研究领域的专题进行培训,可获得广东省继续教育Ⅰ类,6学分的继续医学教育证书。     

The human drama of genetics: 'hard' and 'soft' media representations of inherited breast cancer

This paper examines media coverage of 'breast cancer genetics', and explores its implications for public understanding. We present a content analysis of coverage in British newspapers and look at a variety of popular forms, including women's magazines, television soap opera and radio drama. Genetic/inherited risk receives a great deal of coverage across a wide range of media formats and outlets. Much of this attention has focused on individuals from 'high risk families' and dilemmas around prophylactic mastectomies. Through examining media coverage, combined with interviews with media personnel and their sources, we show why this story proved so attractive to the media and highlight the different production values which influence coverage. Finally, we introduce preliminary findings from focus group discussions to demonstrate how such 'human interest' framing has engaged audience attention and influenced public understandings. The paper concludes by highlighting the implications for analysing, predicting, and engaging with, media representations of science.     

Worker education in the primary prevention of occupational dermatoses

This paper reports the evaluation of a skin care education programmeconducted on a fine chemicals manufacturing site where over1,000 employees are located. Approximately 60% are involvedin chemical manufacture. Over a 12 month period production staffreceived training in prevention of occupational dermatoses linkedto a site-wide poster initiative. The incidence of new casesof occupational dermatoses fell from 0.055 (70 cases in 1,277employees) to 0.021 (27 cases in 1,277 employees) before andafter the intervention respectively (p<0.0001). After otherfactors such as chemicals handled, observer bias and changesin reporting related to socioeconomic climate were taken intoaccount it is concluded that this study demonstrates the importanceof worker education as a tool for primary prevention of disease.Training materials such as video and poster presentations maybe effectively used in the chemical manufacturing industry asan adjunct to prevention and control of exposure to substanceshazardous to the skin. Such methods may also be used in otherindustries where there are significant risks of dermatoses.     

Regional Variation in Travel-related Illness acquired in Africa,March 1997–May 2011

To understand geographic variation in travel-related illness acquired in distinct African regions, we used the GeoSentinel Surveillance Network database to analyze records for 16,893 ill travelers returning from Africa over a 14-year period. Travelers to northern Africa most commonly reported gastrointestinal illnesses and dog bites. Febrile illnesses were more common in travelers returning from sub-Saharan countries. Eleven travelers died, 9 of malaria; these deaths occurred mainly among male business travelers to sub-Saharan Africa. The profile of illness varied substantially by region: malaria predominated in travelers returning from Central and Western Africa; schistosomiasis, strongyloidiasis, and dengue from Eastern and Western Africa; and loaisis from Central Africa. There were few reports of vaccine-preventable infections, HIV infection, and tuberculosis. Geographic profiling of illness acquired during travel to Africa guides targeted pretravel advice, expedites diagnosis in ill returning travelers, and may influence destination choices in tourism.     

The design of hazard risk assessment matrices for ranking occupational health risks and their application in mining and minerals processing

Two hazard risk assessment matrices for the ranking of occupational health risks are described. The qualitative matrix uses qualitative measures of probability and consequence to determine risk assessment codes for hazard-disease combinations. A walk-through survey of an underground metalliferous mine and concentrator is used to demonstrate how the qualitative matrix can be applied to determine priorities for the control of occupational health hazards. The semi-quantitative matrix uses attributable risk as a quantitative measure of probability and uses qualitative measures of consequence. A practical application of this matrix is the determination of occupational health priorities using existing epidemiological studies. Calculated attributable risks from epidemiological studies of hazard-disease combinations in mining and minerals processing are used as examples. These historic response data do not reflect the risks associated with current exposures. A method using current exposure data, known exposure-response relationships and the semi-quantitative matrix is proposed for more accurate and current risk rankings.     

Psychopathological features of a patient population of targets of workplace bullying

BACKGROUND: A strong association between workplace bullying and subsequent anxiety and depression, indicated by empirical research, suggests that bullying is an aetiological factor for mental health problems. AIMS: To evaluate levels of stress and anxiety-depression disorder developed by targets of workplace bullying together with outcome at 12 months and to characterize this population in terms of psychopathology and sociodemographic features. METHODS: Forty-eight patients (36 women and 12 men) meeting Leymann Inventory of Psychological Terror criteria for bullying were included in a prospective study. Evaluations were performed at first consultation and at 12 months using a standard clinical interview, a visual analogue scale of stress, the Hospital Anxiety and Depression (HAD) scale, the Beech scale of stress in the workplace and a projective test (Picture-Frustration Study). RESULTS: At first consultation, 81% of patients showed high levels of perceived stress at work and 83 and 52% presented with anxiety or depression, respectively. At 12 months, only 19% of working patients expressed a feeling of stress at work. There was a significant change in symptoms of anxiety while there was no change in symptoms of depression. Stress at work and depression influenced significatively capacity to go back to work. At 12-month assessments, workers showed a significantly better score on the HAD scale than non-workers. Over half the targets presented a neuroticism-related predominant personality trait. CONCLUSION: Workplace bullying can have severe mental health repercussions, triggering serious and persistent underlying disorders.     

The rise and fall in incidence of malignant mesothelioma from a British Naval Dockyard, 1979-1999

BACKGROUND: The incidence of malignant mesothelioma in Britain is predicted to rise over the next 15-25 years because of past failure to protect the workforce against inhalation of asbestos. In British Naval dockyards, alternative insulation materials and respiratory protection were introduced from the mid-1960s. Aims This study was carried out to investigate the effects of these control measures on mesothelioma deaths in dockyard workers. METHODS: Cases of mesothelioma of the pleura and peritoneum between 1979 and 1999 in workers from the Devonport Naval Dockyard, south-west England, were sought from coroners' and medico-legal records. RESULTS: Three hundred and one cases were identified, 7% peritoneal. The peak incidence occurred in 1991 with 25 cases per annum (quadratic model fit R(2) = 74.2%, P < 0.001) and we predict that by 2003 the incidence will fall to fewer than five cases per annum. The mean time between first exposure and presentation was 48.5 years [95% confidence interval (CI) = 47.3-49.8], but this was significantly shorter in the more heavily exposed trades, when compared with the less heavily exposed (42 years, 95% CI = 39.0-45.0, versus 49.5 years, 95% CI = 48.2-50.9). Those with higher exposure were also at significantly greater risk of peritoneal disease (P < 0.023, Fisher's exact test). CONCLUSION: The reduction in incidence of mesothelioma is greater than can be accounted for by reduction in numbers of dockyard workers over the last 50 years. Changes in insulation materials and improved industrial hygiene measures introduced into the Devonport Dockyard from the mid-1960s have resulted in an earlier decline in the incidence of malignant mesothelioma than that predicted for the British workforce as a whole.     

Die sogenannte Vinylchlorid-Krankheit—eine berufsbedingte Systemsklerose?

Zusammenfassung Es wurden 13 Arbeiter untersucht, die zwischen 1 3/4 und 18 Jahren in einem PVC-herstellenden Betrieb beschäftigt waren. 8 von ihnen wiesen sklerodermieartige Hautveränderungen (Abb. 2) auf, die histologisch charakterisiert sind durch Verbreiterung und Homogenisierung der kollagenen Faserbündel (Abb. 3 u. 4) sowie Fragmentation und Rarefizierung der elastischen Fasern (Abb. 5). Bei 7 Patienten bestanden trommelschlegelartige Auftreibungen einzelner Fingerendphalangen (Abb. 1). 11 Patienten zeigten Durchblutungsstörungen der Extremitäten (4 von diesen ein Raynaud-Syndrom) und 6 Patienten Acroosteolysen einzelner Fingerendphalangen (Abb. 6, Tabellen 1–3).Darüber hinaus bestand bei allen Patienten eine Thrombocytopenie, bei 12 Patienten eine Splenomegalie, bei 11 Patienten eine Einschränkung der Leberfunktion (erhöhte BSP-Retention). An der Leber ließ sich histologisch bei den 5 laparoskopierten Patienten eine deutliche Fibrosierung der Portalfelder nachweisen. Bei 4 Patienten bestanden Oesophagusvaricen (Tabellen 4 u. 5). 8 Patienten zeigten eine Partialinsuffizienz mit Hinweisen für vorwiegend restriktive Veränderungen.Die hier beschriebenen Veränderungen gehen weit über das bisher bekannte Acroosteolysesyndrom hinaus. Es wird der dringende Verdacht geäußert, daß langfristige Vinylchlorid-Exposition dieses komplexe Krankheitsbild verursacht. Daher wird für diese systemische Krankheit die Bezeichnung Vinylchlorid-Krankheit vorgeschlagen.Wir danken Frau E. Voigtländer für die Herstellung der klinischen und histologischen Abbildungen.     

Organophosphate toxicity and occupational exposure

The ubiquitous organophosphates present a continuing health hazard in agriculture, public health eradication programmes and as chemical warfare agents. Despite significant progress in understanding the potential mechanisms of toxicity far beyond the commonly accepted mechanism of cholinesterase inhibition in intentional exposures, the precise health effects following occupational exposures are yet to be completely defined. A much greater understanding exists of the clinical features of organophosphate poisoning. These are characterized by a triphasic response involving an initial acute cholinergic phase, an intermediate syndrome (both associated with high mortality) and a disabling but non-lethal delayed polyneuropathy. The delayed polyneuropathy may occur in the absence of the cholinergic or intermediate phases. However, progress is still required in order to improve the quantification and assessment of occupational exposures and the implementation of appropriate preventive measures. Finally, evidence-based guidelines for appropriate or optimal therapeutic interventions following poisoning are required urgently and collaborative work with colleagues in developing countries, where the occurrence of organophosphate exposures is more frequent, may provide the answers.     

Miliaria rubra of the lower limbs in underground miners

This report documents a case series of miliaria rubra of the lower limbs in miners at a deep underground metalliferous mine in tropical arid Australia. During the summer months of February and March 1999, all cases of miliaria rubra of the lower limbs in underground miners seen at the mine's medical centre were clinically examined and administered a questionnaire. Twenty-five patients were seen, an incidence of 56.4 cases per million man-hours. Miliaria rubra was most often located between the ankle and knee (88% of cases). Twenty-four percent had concurrent folliculitis and 20% had concurrent tinea. Thirty-two percent had a personal history of asthma. Walking through ground-water and splashing of the legs was common. Three to 4 weeks of sedentary duties in air conditioning was generally required to achieve resolution of miliaria rubra. The incidence of miliaria rubra of the lower limbs is 38% of the incidence of heat exhaustion at the same mine. The length of disablement is greater, however. Atopics may be at increased risk of miliaria rubra. Control measures are discussed.     

Planning research

The starting point for any research project should be a question.Once this has been defined and the relevant scientific literaturereviewed, a protocol should be drawn up. This will be used notonly as a guide to the conduct of the study and in the preparationof the final report, but also in seeking any financial supportand approvals that are required for the investigation. A protocolis normally arranged in sections covering the background tothe study, the question(s) that it will address, the methodsthat will be used for the collection and analysis of data, thestatistical power of the investigation (where relevant), anyethical considerations, and the financial input that will beneeded. A pilot study is often helpful where aspects of thestudy method are untried or of uncertainvalidity.