Systematic review: lamivudine prophylaxis for chemotherapy-induced reactivation of chronic hepatitis B virus infection

BACKGROUND: Reactivation of hepatitis B virus infection in asymptomatic hepatitis B surface antigen carriers undergoing chemotherapy or immunosuppressive therapy is a well-documented and potentially fatal complication. Data supporting the use of lamivudine for primary prophylaxis have emerged, but its use remains controversial and is not standardized. AIM: To review current randomized-controlled trials, randomized trials and prospective case series to provide a clinically applicable, evidence-based recommendation. METHODS: The published literature was identified using a MEDLINE/PubMed search with secondary review of cited publications, and inclusion of all prospective studies. RESULTS: In nine prospective trials and one randomized-controlled trial, the rate of hepatitis among subjects receiving lamivudine prophylaxis ranged from 0% to 20% (16 of 173, 9.2%), compared with 33-67% among controls. Of patients receiving prophylaxis, 0-24% (15 of 173, 8.7%) developed hepatitis B virus reactivation, compared with 29-56% of controls. Three reactivation-related mortalities were reported (one receiving prophylaxis, two controls). No patients withdrew secondary to toxicity or development of lamivudine-resistant mutations. CONCLUSIONS: The available data show a four- to sevenfold decrease in the rate of hepatitis and hepatitis B virus reactivation in patients who receive lamivudine prophylaxis. It is thus recommended that all hepatitis B surface antigen carriers receive lamivudine, or a comparable anti-viral agent, as prophylaxis from the initiation of chemotherapy until at least 1 year following its completion.     

Immunology of hepatitis B virus infection

The hepatitis B virus (HBV) is believed widely to be noncytopathic in its natural host, man, although this may not be true in animal models, for example the transgenic mouse where expression of HBsAg is associated with the onset of hepatocellular degeneration and necrosis. The basis for this belief is simply that in the earlier stages of chronic HBV infection, when viral replication is most efficient, 'patients' remains asymptomatic and a liver biopsy reveals no evidence of inflammation or parenchymal liver damage. The major features of immunological interest in HBV infection are first that a proportion of those exposed to the virus become chronically infected and second that once chronic infection is established, most will gradually eliminate the nucleocapsid antigen from the liver, while the envelope antigens continue to be expressed. During the elimination of nucleocapsid antigens, many patients develop permanent liver damage.     

丁型肝炎病毒感染与乙型肝炎关系的研究

我国是病毒性肝炎高发区,有散在性和地方性感染两种形式．现在研究认为,HDV是缺陷病毒,其衣壳为HBSAg,从而决定了HDV只能感染HBSAg阳性者,而我国众多的HBsAg携带者,都是HDV的攻击目标。为了解丁型肝炎病毒（HDV）在我地的感染状况与乙型肝炎的关系．我们对1000名乙型肝炎患者进行了初步调查研究,现报道如下．1材料与方法1．1标本来源被检标本均来自佳市传染医院1991－01~1999－06住院的乙型肝炎患者血清。其中男750例,女25O例。男女之比为31．年龄6个月～72岁。诊断标准依据1990年上海全国病毒性肝炎学术会议修订的诊断标…     

Patterns of hepatocellular carcinoma development in hepatitis B virus and hepatitis C virus related cirrhosis.

To compare incidence, risk factors and morphologic pattern of hepatocellular carcinoma (HCC) development in hepatitis B virus (HBV) and hepatitis C virus (HCV) related cirrhosis, 401 patients were followed prospectively by periodic ultrasound examination for 14-189 months (mean: 84.8+/-36.7). During follow-up, 77 (19.2%) patients developed HCC, with 5 and 10 year cumulative incidence of 10 and 27.5%, respectively. The risk of HCC was significantly higher in HBV and HCV co-infected patients (P=0.014) compared to those with single HBsAg or anti-HCV (antibodies to hepatitis C virus) positivity. In anti-HCV positive cases the annual risk of HCC increased from 2% in the first 5 year period to 4% in the third 5 year period, while it decreased from 2 to 0% in the same time periods in the HBsAg positive group. By Cox's regression, age above 59 years (P=0.001), male sex (P=0.09), longer duration (P=0.04) and more advanced stage (P=0.01) of cirrhosis, lower platelets count (P=0.001) and higher ALT levels were significant risk factors for HCC in anti-HCV positive patients, while only high alpha-fetoprotein (AFP) levels during follow-up (P=0.04) was a significant risk factor for HCC in HBsAg positive cases. The pattern of HCC was nodular in 63 (81.8%) patients and infiltrating in 14 (18.2%), and the former type was associated with older age (P=0.0001), longer duration (P=0.002) and more advanced stage (P=0.0001) of cirrhosis but not with the viral etiology of disease. In contrast, development of infiltrating HCC was unrelated to age and disease duration and stage, and was associated with male sex (P=0.01), HBV infection (P=0.06) and HBV and HCV co-infection (P=0.0001). Our results indicate different incidence profile, risk factors and patterns of morphogenesis of HCC development in HBV and HCV associated cirrhosis, suggesting different mechanisms of carcinogenesis.     

恩替卡韦治疗代偿期乙型肝炎肝硬化的疗效与安全性观察

目的观察恩替卡韦治疗代偿期乙型肝炎肝硬化患者的疗效与安全性。方法 60例乙型肝炎肝硬化代偿期患者接受恩替卡韦治疗72周,观察患者生化学指标、病毒学指标和组织学指标的变化情况。结果所有患者均没有发展到失代偿期,生化学指标、病毒学指标和组织学指标均有明显改善,差异有统计学意义(P<0.05)。结论代偿期乙型肝炎肝硬化患者选用恩替卡韦有良好的疗效及安全性。     

拉米夫定预防鼻咽癌治疗相关性乙肝病毒再激活的疗效分析

目的探讨拉米夫定预防鼻咽癌治疗相关性乙型肝炎病毒再激活的疗效。方法收集2008年3月至2009年3月初治HBsAg（＋）鼻咽癌患者51例,将其分成两组：拉米夫定预防治疗组（A组,n=26例）和非预防治疗组（B组,n=25例）。A组患者在鼻咽癌放化疗前一周开始口服拉米夫定100mg／d,至放化疗结束后8w;B组未给予预防性口服拉米夫定。比较两组鼻咽癌治疗相关性肝炎发生率、HBV再激活率及放化疗中断率。结果鼻咽癌放化综合治疗期间,预防治疗组和非预防治疗组治疗相关性肝炎发生率、HBV再激活率及放化疗中断率分别为3．85％与32％、0％与28％、19．2％与56％,两组比较差异有显著性（P值〈0．05）。结论拉米夫定预防性治疗能够显著降低鼻咽癌治疗相关性肝炎的发生率、HBV再激活率及放化疗中断率。     

Fatal hepatitis during Epstein-Barr virus reactivation

Fulminant hepatitis by Epstein-Barr virus is a rare event which is predominantly due to primary infection. We report a rare case of fatal hepatic failure due to Epstein-Barr virus reactivation in a 19-year-old boy who was taking oral steroids. Transaminase peak and the fulminant course of the disease began soon after steroid interruption. Epstein-Barr virus reactivation was diagnosed on the basis of past clinical history of heterophile-positive infectious mononucleosis, a high titer of IgG anti Epstein-Barr virocapsidic antigen, slight elevation of anti-virocapsidic IgM, a high titer of anti-EA IgG antibodies and elevated viral load in serum measured by polymerase chain reaction. It is concluded that Epstein-Barr virus should be considered as a possible etiological agent of fulminant hepatitis.     

乙型肝炎病毒感染与食管、胃疾病的关系

目的:探讨乙型肝炎病毒感染与食管、胃疾病关系。方法:2004年4～12月因消化不良症状而行内镜检查患者分成2组,A组为HBsAg阳性患者71例,B组为HBsAg阴性患者93例,对结果进行统计学处理分析。结果:消化性溃疡总的发生率31.7%,其中A组为42.3%(30/71),B组为23.7%(22/93)(x2=6.55,P<0.05)。总HP感染率为55.5%,其中A组为64.8%(46/71),B组为48.4%(45/93)(x2=3.95,P<0.05)。糜烂性胃炎的总发生率为23.2%,A组为33.8%(24/71),B组为15.1%(14/93)(x2=8.02,P<0.01),食管癌、胃癌总发生率3.7%,其中A组7.0%(5/71),B组1.1%(1/93)(校正x2=442,P<0.05)。结论:HBV感染与消化性溃疡、HP感染、糜烂性胃炎、上消化道肿瘤等疾病密切相关,须重视对HBV感染患者的胃、食管疾病。     

Novel treatment options for hepatitis B virus infection

Chronic hepatitis B virus (HBV) infection affects between 350 and 400 million people globally. Interferon-alpha, lamivudine and adefovir (Hepsera) are approved for the treatment of chronic hepatitis B; however, the use of interferon-alpha is limited. Lamivudine and adefovir have excellent antiviral activity and oral bioavailability, although viral rebound after cessation of therapy and development of resistance after long-term therapy with lamivudine are major clinical limitations. Adefovir has proven to be effective against lamivudine-resistant strains in vitro and in vivo. The various steps of HBV replication provide opportunities for new antiviral drugs to interact with the virus. Recent developments, including new antivirals that interfere with viral DNA replication, hold promise for the future. Sustained reduction in viral load and improved treatment of chronic HBV infection could, in future, be achieved by the development of new drugs with different mechanisms of action and resistance profiles, and with combination therapy involving two or more nucleosides with or without immunomodulators.     

预防血液透析患者乙型肝炎与丙型肝炎病毒感染的效果观察

目的 采取有效措施预防维持性血液透析患者乙型肝炎、丙型肝炎病毒感染的发生.方法 观察2008年9月至2011年3月在本院行维持性血液透析患者,每6个月化验1次乙型肝炎五项、丙型肝炎抗体指标,共6次.结果 36例维持性血液透析患者未再出现新的乙型肝炎、丙型肝炎病毒感染病例.结论 采取有效措施可预防维持性血液透析患者乙型肝炎、丙型肝炎病毒感染的发生.     

血T淋巴细胞亚群水平与乙型肝炎病毒再激活关系的研究

目的 探讨乙型肝炎(乙肝)病毒再激活与血T淋巴细胞亚群变化的关系.方法 使用流式细胞仪(流式细胞EPICS XL)检测40例慢性乙肝病毒携带者与35例乙肝病毒再激活患者T淋巴细胞亚群( CD3、CD4、CDs、CD4/CDs)水平.结果 乙肝病毒再激活患者CD3 、CD4及CD4/CDs均显著低于慢性乙肝病毒携带者[(71.31±5.20)％与(68.57±6.10)％、(37.82±4.90)％与(32.12±5.93)％、(1.37±0.28)与(1.18±0.43),均P＜0.05].结论 CD3、CD4低水平及CD4/CDs比例的明显下降可能是引起乙肝病毒再激活的重要原因之一.     

肇庆市某高校新生乙肝病毒感染调查分析

目的 调查分析某高校学生乙肝病毒感染情况.方法 对2014年、2015年某校人校的10500名新生进行问卷调查(乙肝知识、态度、行为),并采取酶联吸附法检测患者的乙型肝炎表面抗原(HBsAg)感染情况.结果 不同性别、民族、专业和区域的同学都意识到乙肝是一种严重的疾病,男性同学及有接触同学知晓更高.对于乙肝防治知晓率基本在50％以上,在性别和区域无明显差异,民族和经历有一定差异.对乙肝患者的态度相对理性,其他民族的学生对待态度有点畏惧和排斥.2015级新生ALT阳性患者相对于2014级显著下降(P＜0.05),其中,HBsAg阳性新生数也随着降低,差异无统计学意义(P＞0.05),AST阳性者例数无明显变化(P＞0.05).结论 我国大学生对乙肝了解程度逐渐提高,乙肝病毒感染也较低,但是仍然需要加大对乙肝健康教育的力度,从根本上铲除其危害.     

隐匿性乙型肝炎病毒感染的临床分析

目的 了解乙型肝炎血清免疫学标志物（HBVM）阴性而有病毒复制者的产生原因。方法 65例肝活检患者中16例血清HBVM（包括HBsAg、抗HBs、HBeAg、抗HBe及抗HBc）2次以上检测全部阴性。6例血清ALT水平多次检测正常,结合病史诊断为HBV携带者;8例诊断为慢性乙型肝炎;2例为肝硬化。结果 6例HBV携带者中4例病毒负荷10^4～10^5 copies／ml,炎症及纤维化程度为G1、S1 8例慢性肝炎中4例血清病毒〉10^5～10^6 copies／ml,2例肝硬化者低于10^4 copies／ml。免疫组化肝组织所见有HBsAg或／和HBcAg表达。结论隐匿性HBV感染的发生可能有多种机制参与。     

甲胎蛋白检测在乙型肝炎病毒感染患者中的意义

目的探讨甲胎蛋白（AFP）检测在HBV感染相关疾病中的临床意义和作用。方法检测无症状HBV携带组57例,慢乙肝组74例,慢乙肝合并肝硬化组63例,慢乙肝合并肝癌组45例和健康组40例血AFP水平,用logistic回归方法分析影响AFP升高的因素,用Spearmen等级相关方法分析AFP升高幅度与疾病严重程度的相关性。结果与健康组相比,慢性乙型肝炎、慢乙肝合并肝硬化、慢乙肝合并肝癌患者血中AFP、ALT、AST、TBIL水平明显增高．其中以慢乙肝合并肝癌患者血中AFP、TBIL水平最高,其次为慢乙肝合并肝硬化患者;ALT和AST在慢性乙型肝炎、慢乙肝合并肝硬化患耆血中水平最高,其次为慢乙肝合并肝癌患者。回归分析结果提示慢乙肝、饮酒量、饮酒年数、年龄及ALT和AST与AFP〉20μg／L相关;慢乙肝与AFP〉200μg／L相关;AST与AFP〉400燃／L相关;总胆红素及直接胆红素与AFP〉1000μg／L相关。等级相关分析结果发现AFP升高幅度与疾病的严重程度有相关性（r=0．533,P〈0．01）。结论AFP升高在不同HBV感染相关疾病组的临床意义有所不同;慢乙肝、饮酒、年龄及肝功能等因素可影响AFP的水平;AFP〉400μg／L高度提示肝癌的发生,动态检测AFP水平对判断HBV感染患者的预后具有重要的意义。     

郑州地区乙肝感染趋势变化研究

目的:探讨乙肝病毒(HBV)感染趋势及变化规律.方法:采用ELISA方法检测"乙肝两对半"及HBcAb-IgM.结果:在郑州地区门诊乙肝随诊人群中,男性明显多于女性;HBV感染人数和复发人数呈逐年上升的趋势,男性重于女性:HRsAg阳性感染人数和复发人数也呈逐年上升趋势,同样,男性多于女性;乙肝患者感染情况呈现感染模式多样化.由2003年的16种增加到2006年的30种.结论:郑州地区乙肝感染情况严重并且重于全国平均水平,需要加强郑州地区的乙肝防治工作.     

Antiviral therapeutic efficacy of foscarnet in hepatitis B virus infection

Foscarnet (PFA), a viral DNA polymerase inhibitor, is a clinical agent for herpes viruses. The goal of the study was to evaluate the therapeutic efficacy of PFA in hepatitis B virus (HBV) infection. Intravenous infusion of PFA (1 g/day) for 4 weeks significantly reduced serum HBeAg (p<0.01) and HBV DNA copies (p<0.05) in 31 patients who were diagnosed with active chronic HBV infection (CHB) and had not received antiviral treatment previously. Alanine aminotransaminase (ALT), aspartate aminotransaminase (AST) and gamma glutamyl transpeptidase (gamma-GT) of the patients declined (p<0.001, 0.001 and 0.01, respectively). Kidney function (blood creatinine and urea nitrogen) remained unchanged. Another 21 lamivudine-resistant CHB patients with mutations at the tyrosine-methionine-aspartate-aspartate motif (YMDD) displayed a response to PFA similar to that mentioned above, with reductions in HBeAg (p<0.05), HBV DNA (p<0.01) and liver enzymes (ALT and AST, p<0.001; gamma-GT, p<0.05). Moreover, PFA reduced serum HBeAg (p<0.01), HBV DNA (P<0.05), AST (p<0.05) and ALT (p<0.02) in a cohort of 13 severe CHB patients with advanced liver damage. PFA was also evaluated in vitro and in vivo. PFA inhibited HBV DNA replication in HBV-transfected human HepG2 cells (2.2.15 cells) with reduced amount of HBV RC-DNA and DS-DNA. In the duck HBV-infected ducklings, PFA reduced viral DNA and duck HBsAg in the serum (p<0.01 for both).     

Clinical course of hepatitis B virus infection during pregnancy

Background  For women with hepatitis B virus (HBV) infection, little is known about the natural progression of the disease during pregnancy or its impact on pregnancy outcomes.
Objectives  To investigate the natural progression of HBV infection during pregnancy or its impact on pregnancy outcomes.
Methods  In this retrospective cohort study, we reviewed medical records of all patients who were pregnant and presented with HBsAg-positivity between 2000 and 2008 at a community gastroenterology practice and a university hepatology clinic. Maternal characteristics were analysed according to maternal and perinatal outcomes.
Results  A total of 29 cases with at least 2 measurements of either HBV DNA or alanine aminotransferase (ALT) levels were included. Older age was the only predictor of a trend towards higher risk of an adverse clinical outcome [OR = 1.21 (0.97–1.51), P  =   0.089], defined as either a negative foetal outcome (premature delivery, spontaneous abortion), or a negative maternal outcomes (gestational diabetes mellitus, pre-eclampsia, hepatic flare, liver failure). This trend for age remained even after adjusting for baseline ALT. Baseline serum HBV DNA, ALT, hepatitis B e antigen status, gravida and parity were not significant predictors for adverse clinical outcomes. Four patients developed liver failure.
Conclusions  Maternal and neonatal outcomes are highly variable in this clinic-based patient cohort. Severe complications due to HBV infection can occur during pregnancy in previously asymptomatic patients. It is unclear how generalizable the results observed in this cohort would be to the general population; therefore, further studies are needed to identify reliable predictors for significant adverse outcomes and until more data are available, pregnant patients with HBV infection should be monitored with periodic serum HBV DNA and ALT levels.     

医护人员乙型肝炎病毒感染现况调查及防护

目的：分析医务人员乙型肝炎病毒（HBV）感染的流行病学特点，探讨有效的控制策略。方法：对448名临床医务人员和256名非临床人员进行HBV血清流行病学调查。结果：内、外科医务人员HBV感染率分别为82．8％和87．7％，高于非临床人员的73．4％（P〈0．05）；护士组HBV感染率高于医生组（P〈0．05），其中外科护士HBV感染率为90．5％，远高于外科医生的80．0％（P〈0．05）。结论：综合性医院乙型肝炎（乙肝）的防治对象是一线临床医务人员，且重点为外科护士，控制策略为三级预防。     

Antiviral effects of PNA in duck hepatitis B virus infection model

AIM: To study the efficacy of antiviral treatment with PNA for the duck model of HBV (DHBV)-infected ducks. PNA is a 2-amine-9-(2,3-dideoxy-2,3-dihydro-beta-D-arabinofuranosyl)-6-methoxy-9H-purine. METHODS: The Sichuan Mallard ducklings in the hepatitis B virus model were treated with PNA, a new antiviral agent. DHBV DNA from the blood serum and liver tissues were measured at 0, 5, and 10 d during the treatment and at 3 d withdrawal by real-time PCR. The duck hepatitis B surface antigen (DHBsAg) in the liver cells was observed by Immunohistochemistry (IHC). Pathological changes in the liver tissues were also observed. Control group I was administered with distilled water and control group II was administered with 3-thiacytidine. Treatment group I was administered with PNA at a dose of 40 mg/kg and treatment group II was administered perorally (po) with PNA at a dose of 80 mg/kg. Treatment group III was administered with PNA at a dose of 20 mg/kg and treatment group IV was intravenously administered with PNA at a dose of 40 mg/kg. Each group contained 15 ducklings. RESULTS: PNA can significantly lower the DHBV replication levels in serum and liver. Compared with control group II, there were no significant differences in inhibiting efficacy in treatment groups I and III (P>0.05) and there were significant differences in inhibiting efficacy in treatment groups II and IV (P<0.05). Interestingly, significant differences were observed at 3 d withdrawal. The DHBV replication levels in each group slightly increased at 3 d withdrawal, but rebounded slightly in the PNA treatment groups than in control group II (P<0.05). The DHBV replication levels in the treatment groups were lower than in control group I. The DHBV replication levels in sera had a positive relationship with that in the liver, but the DHBV replication levels in the liver was lower than that in sera. Pathological changes in the treatment groups were obviously improved and the changes were associated with liver viral DNA levels. CONCLUSION: The results demonstrate that PNA is a strong inhibitor of DHBV replication in the DHBV-infected duck model.