Hepatitis A virus-associated fulminant hepatitis with human immunodeficiency virus coinfection

Hepatitis A virus (HAV) commonly causes acute hepatitis in humans and is transmitted through the fecal-oral route or by ingestion of contaminated food or water. HAV infection generally follows a self-limiting course; it can seldom cause fulminant hepatitis that increases the risk of mortality. To the best of our knowledge, this is the first reported fatal case of fulminant hepatitis caused by HAV in a 40-year-old male with human immunodeficiency virus (HIV) infection. The HAV genotype in this case was IA, which has recently become common globally among people living with HIV (PLWHIV), intravenous drug users, and homeless people especially in developed countries. His HIV infection was stabilized by antiretroviral drugs and his CD4 values were stable. He developed acute hepatic encephalopathy, did not respond to repeated plasma exchange therapy, and died rapidly. It is known that HIV co-infection sometimes leads to fulminant non-HAV hepatitis, although evidence supporting a correlation between fulminant hepatitis A risk and HIV infection is still lacking. This case demonstrated the fatal risk of HAV infection in PLWHIV; it was suggested that education about appropriate preventive measures and vaccination are important for preventing HAV infections among PLWHIV.     

乙肝肝硬化肝胆湿热及肝肾阴虚证物质基础研究＊

目的 运用代谢组学技术分析乙肝肝硬化患者肝肾阴虚及肝胆湿热两种典型证候（同病异证）的血清差异代谢产物及其代谢通路，探寻虚、实两种典型证候的内在物质基础，以期从代谢水平上为中医证候分类提供客观依据。方法 对符合纳入标准的111例不同证候的乙肝肝硬化患者（肝胆湿热证40例，肝肾阴虚证41例，隐证(无证可辨）者30例）中医症状及体征进行描述性分析，发现两种不同证型的临床信息分布规律及证候特征；采用气相色谱-飞行时间质谱联用（GC-TOF/MS）技术对乙肝肝硬化患者，以及与之相匹配的60例健康人的血清样本进行检测，经非监督的主成分分析（Principal Components Analysis，PCA）、有监督的偏最小二乘判别分析（Partial Least Square Discriminant Analysis，PLS-DA）及监督的正交偏最小二乘法（Orthogonal Partial Least SquareDiscriminant Analysis，OPLS-DA）分析，找出与乙肝肝硬化疾病本身及其两种典型证候相关的差异性物质；运用MetaboAnalyst 3.0数据库，寻找并解析肝胆湿热及肝肾阴虚虚实两种证候间差异性物质的相关代谢通路。结果 （1）肝胆湿热证中出现频率较高（50%以上）的症状为小便色黄，口干，口苦，口臭或有异味等。肝肾阴虚证中出现频率较高的症状为口干、腰酸、乏力、腿软等。两证共见症/征为口干、尿黄、易怒、舌红。（2）各组间丙氨酸氨基转移酶（Alanine Aminotransferase,ALT）数值无统计学差异（P > 0.05）；与健康组比较，隐证组中白蛋白（Albumin，ALB），肝胆湿热证中总胆红素（Total Bilirubin，TBil）、直接胆红素（Direct Bilirubin，DBil）、谷草转氨酶（Aspartate Transaminase，AST）、碱性磷酸酶（Alkaline Phosphatase，ALP）、谷氨酰转肽酶（Gamma-Glutamyl Transpeptidase，GGT）、总胆汁酸（Total Biliary Acid，TBA）及ALB，肝肾阴虚证TBil、ALP、GGT、TBA、ALB值差异均有统计学意义（P < 0.05）；与隐证比较，肝胆湿热证TBil、DBil、AST、ALP、TBA、ALB，肝肾阴虚证TBA、ALB差异有统计学意义（P < 0.05）；肝胆湿热证与肝肾阴虚证相比，TBil、DBil差异有统计学意义（P < 0.05）。（3）代谢组学检测及代谢通路分析，发现各组之间代谢谱均有良好的区分，并获得各组间的差异性物质。发现肝胆湿热及肝肾阴虚两典型证的共同物质10个，去除疾病（隐证）的信息，则得到两证共同物质6个，涉及的代谢通路为甘氨酸、丝氨酸及苏氨酸代谢和苯丙氨酸代谢；同时，分别获得两证各自特异性的代谢物质各8个，分别涉及亚油酸代谢和甘氨酸、苏氨酸及丝氨酸代谢。结论 运用代谢组学技术，发现肝胆湿热及肝肾阴虚不同证之间既存在病的共同物质（同病），也存在证的差异物质（异证），从而在代谢层面上为中医证候分类的科学性提供科学依据。     

Directly observed hepatitis C treatment with opioid substitution therapy in community pharmacies: A qualitative study

BackgroundThe hepatitis C virus (HCV) will only be eliminated through successful engagement with people who inject drugs (PWID), however some of this population experience socioeconomic and individual issues that can lead to poor HCV treatment adherence. A key sub-group of (PWID) are those who receive opioid substitution therapy (OST). In Australia, OST is most often delivered under direct supervision by a community pharmacist every day or multiple times a week. This regular interaction could be an ideal opportunity to enhance direct-acting antiviral (DAA) treatment adherence under directly observed therapy (DOT) by the pharmacist.AimThe aim of this study was to explore the perspectives of OST patients with a lived experience of HCV to understand whether or not dispensing DAAs in the same way as, or simultaneously with OST would benefit HCV treatment.MethodsData collection occurred from June to August 2017. Semi-structured interviews were conducted with a sample of PWID living with HCV and on OST programs (n = 12) in Melbourne, Australia. Interviews were voice recorded and transcribed in verbatim. Interpretive phenomenology guided analysis of the data.ResultsThemes reported by participants that provide insight into the suitability of DOT of DAAs include: Adherence and non-adherence to DAA treatment; Mixed views towards DOT of DAAs; Experiences and perceptions of OST providers; and Perceived stigma in the pharmacy.ConclusionsCommunity pharmacies offering OST may be an effective place for DOT of HCV treatment, but is likely only to benefit people who face significant challenges to adherence. We suggest that a positive pharmacist-patient relationship, high OST adherence, and commitment to reducing stigma in the pharmacy would be necessary for the intervention to be effective. Further research is needed to evaluate the expanded-role of community pharmacies in improving DAA adherence and eliminating HCV.     

深圳地区HBV核酸检测反应性献血者两种归队模式风险评估研究

目的评估HBV核酸检测反应性献血者归队风险,为采供血机构制定献血者归队策略提供依据。方法对ELISA双试剂无反应性、HBV核酸检测反应性献血者进行跟踪检测。每次间隔3个月以上,两次直接静脉采样。归队后再跟踪两次以上献血检测结果。两家血站分别按无门槛自愿原则与增加献血10次以上要求进行采样,并对两种模式归队结果进行比对。结果无门槛自愿归队模式归队前检测3例酶免检测阴转阳(15.79%);增加献血次数门槛归队模式归队成功率88.46%;两种归队模式成功归队后再次出现不合格情况分别为20.00%、13.04%,统计无差异,但归队后人均年献血次数有较大差别。结论酶免检测无反应性而HBV核酸检测反应性被屏蔽献血者无门槛归队模式存在窗口期感染风险。建议将多次献血或固定献血、首次出现酶免检测无反应性而HBV核酸检测反应性被屏蔽的献血者列入归队目标人群。仅以HBsAg+HBV DNA作为HBV核酸检测反应性献血者的归队评价指标存在较大风险,应考虑增加化学发光法等补充试验。     

昆明市2013-2017年丙型病毒性肝炎流行特征及趋势分析

目的分析昆明市2013-2017年丙型病毒性肝炎的流行特征和流行趋势,为科学制定防控策略提供依据。方法运用描述性流行病学方法,统计昆明市2013-2017年丙型病毒性肝炎的发病情况,分析其流行特征和趋势。结果昆明市2013-2017年丙型病毒性肝炎呈现先上升后下降的趋势,2015年达到发病高峰,其发病率高达32.80/10万,总体上2013-2017年丙型病毒性肝炎发病率呈现上升趋势,且肝炎和丙肝以官渡区、五华区和西山区为主要的高发地区;无明显的季节性特点,四季均有发病;易发生丙型病毒性肝炎的人群为35~50岁的农民和家务及待业人员。结论昆明市丙型病毒性肝炎发病状况并不乐观,应加强丙肝防控力度,重点关注高发地区和高发人群,通过有效举措控制丙型病毒性肝炎的发病率。     

Alcohol,tobacco and coffee consumption and liver disease severity among individuals with Chronic Hepatitis B infection in North America

Introduction and objectivesThe prevalence of alcohol, tobacco, and coffee use and association with liver health among North Americans with Chronic Hepatitis B (CHB) infection has not been well described.Materials and methodsThe Hepatitis B Research Network includes an observational study of untreated CHB adults enrolled at 21 sites in the United States and Canada. Alcohol use was categorized as none, moderate, and at-risk based on the definition from the National Institute on Alcohol Abuse and Alcoholism; tobacco use as never, current and former; coffee use as none, 1–2 cups/day, and ≥3 cups/day. Linear regression and linear mixed models were used to associate lifestyle behaviors with ALT and FIB-4 values.Results1330 participants met eligibility: 53% males, 71% Asian and the median age was 42 years (IQR: 34–52). Median ALT was 33 U/L (IQR: 22–50), 37% had HBV DNA <10³ IU/mL, 71% were HBeAg negative, and 65% had a FIB-4 <1.45. At baseline, 8% of participants were at-risk alcohol drinkers, 11% were current smokers and 92% drank <3 cups of coffee/day. Current tobacco and ‘at-risk’ alcohol use, were significantly associated with elevated ALT levels in univariable analyses, however, these associations were not statistically significant when controlling for sociodemographic and HBV characteristics.ConclusionsIn this large diverse cohort of untreated CHB participants, at-risk alcohol use, current tobacco use and limited coffee consumption did not have an association with high ALT and FIB-4 values. In contrast, significant associations were found between the frequency of these lifestyle behaviors and sociodemographic factors.     

Immunogenicity of the hepatitis A vaccine 20 years after infant immunization

To determine the duration of immunity provided by the Hepatitis A vaccination (HepA), we evaluated a cohort of participants in Alaska 20 years after being immunized as infants. At recruitment, participants received two doses of inactivated HepA vaccine on one of three schedules. We conducted hepatitis A antibody (anti-HAV) testing for participants at the 20-year time-point. Seventy-five of the original 183 participants (41%) were available for follow-up. The overall anti-HAV geometric mean concentration was 29.9 mIU/mL (95% CI 22.4 mIU/mL, 39.7 mIU/mL) and 50 participants (68%) remained seropositive (titer ≥ 20 mIU/mL). Using a fractional polynomial model, the predicted percent seropositive at 25 years was 55.3%, 49.8% at 30 years and 45.7% at 35 years, suggesting that the percent sero-positive could drop below 50% earlier than previously expected. Further research is necessary to understand if protection continues after seropositivity diminishes or if a HepA booster dose may become necessary.     

孕期抗病毒治疗结合标准阻断措施对乙型肝炎高病毒载量孕妇所生婴儿母婴传播阻断的影响

目的分析乙型肝炎(乙肝)病毒(Hepatitis B virus,HBV)高载量孕妇孕期HBV脱氧核糖核酸(HBV desoxyribonucleic acid,HBV-DNA)水平和HBVe抗原(HBV e antigen,HBeAg)阳性率以及孕期抗病毒治疗结合标准阻断措施对其所生婴儿母婴传播阻断失败率的影响。方法通过医院信息系统收集HBV-DNA高载量(≥2×10^6IU/mL)孕妇血清学检测结果、抗病毒药物使用等信息,描述HBV-DNA载量和HBeAg阳性率;对HBV-DNA高载量孕妇所生婴儿进行乙肝疫苗(Hepatitis B vaccine,HepB)和乙肝免疫球蛋白(Hepatitis B immunoglobulin,HBIG)联合免疫,在完成第3剂HepB后7月龄-2岁对乙肝表面抗原和HBV-DNA进行随访检测,分析母婴传播阻断失败率。结果共纳入1822名HBV-DNA高载量孕妇,接受、未接受抗病毒治疗分别占75.19%、24.81%。孕妇妊娠期、分娩前HBV-DNA≥1.0×10^8IU/mL比例分别为68.10%(933/1370)、0.15%(2/1370)(χ^2=2692.27,P<0.0001)。接受抗病毒治疗组妊娠期、分娩前HBeAg阳性率分别为96.53%(1001/1037)、96.16%(1251/1301)(χ^2=0.23,P=0.635),未接受抗病毒治疗组妊娠期、分娩前HBeAg阳性率分别为97.70%(298/305)、96.98%(417/430)(χ^2=0.36,P=0.550)。两组HepB和HBIG联合免疫后母婴传播阻断失败率分别为0.42%(3/714)、6.67%(14/210)(χ^2=31.69,P<0.0001)。结论孕妇HBV-DNA高载量以≥1.0×10^8IU/mL为主,孕期抗病毒治疗可显著降低孕妇HBV-DNA载量,结合HepB和HBIG联合免疫可显著降低其所生婴儿HBV母婴传播阻断失败率。     

重组戊型肝炎病毒P179-海藻酸钠/壳聚糖微球混悬制剂的制备及其免疫效果

目的 制备吸附重组戊型肝炎病毒(hepatitis E virus,HEV)P179抗原的海藻酸钠/壳聚糖微球混悬制剂,并观察其免疫效果。方法 乳化法制备海藻酸钠/壳聚糖微球,采用不同海藻酸钠浓度、混合乳化剂添加量、混合乳化剂亲水亲油平衡值设计正交试验,确定最佳制备工艺参数。将重组HEV P179抗原吸附在最佳工艺制备的微球表面,制备吸附重组HEV P179的海藻酸钠/壳聚糖微球混悬制剂,皮下多点免疫BALB/c小鼠,测定其诱导小鼠产生特异性IgG抗体的能力,与同剂量含弗氏佐剂的重组HEV P179免疫制剂对比。结果 经正交试验确定乳化最佳工艺参数为:海藻酸钠质量分数1%、混合乳化剂体积分数2%,混合乳化剂亲水亲油平衡值4。制备的微球平均粒径为6.73 μm(分布范围3.90~9.10 μm,方差1.78 μm),形态较为均一,透射电镜观察结果与双层球体及内部疏松多孔的微球结构特点相符。用此条件制备抗原质量浓度为500 μg/ml的混悬制剂,微球对抗原的吸附率为90.64%。免疫效果观察试验结果表明,皮下多点免疫试验中微球制剂诱导特异性IgG抗体的能力优于含弗氏佐剂抗原。结论 成功制备了吸附重组HEV P179的海藻酸钠/壳聚糖微球混悬制剂,且诱导产生特异性IgG抗体的能力优于含弗氏佐剂抗原,为其在新型实验动物超敏制剂中的应用奠定了基础。