HBsAg levels in HBeAg-positive chronic hepatitis B patients with different immune conditions

AIM:To investigate hepatitis B surface antigen(HBsAg)levels in patients with HBeAg-positive chronic hepatitis B(CHB)and different immune conditions.METHODS:HBeAg-positive CHB patients with different immune conditions were enrolled in this cross-sectional study.These patients were grouped according to the following criteria:immune-tolerant patients,IT group;patients with a mild immune response in the immune clearance phase,IC-Mild group;and patients with a dramatic immune response in the immune clearance phase and exhibiting acute on chronic liver failure(ACLF),ACLF group.All these patients had not previously received antiviral therapy and were enrolled at a pre-settled ratio of2:2:1.Serum HBsAg levels and the correlation between serum HBsAg level and serum hepatitis B virus(HBV)DNA level were evaluated in these groups.RESULTS:In total,180 HBeAg-positive CHB patients[IT group(n=72),IC-Mild group(n=72),and ACLF group(n=36)]were enrolled in this study.The median serum HBsAg levels varied among the groups(P<0.001):IT,4.86 log10IU/mL;IC-Mild,3.97 log10IU/mL;and ACLF,3.57 log10IU/mL.Serum HBsAg level showed a moderate positive correlation with serum HBV-DNA level in the IC-Mild group(r=0.60,P<0.001),but exhibited a weaker correlation in the IT(r=0.52,P<0.001)and ACLF groups(r=0.51,P=0.001).The ratio of HBsAg/HBV DNA did not differ significantly among the IT,IC-Mild,and ACLF groups(medians:0.56,0.55,and 0.56,respectively;P=0.179).CONCLUSION:Serum HBsAg levels varied significantly in HBeAg-positive patients with different immune conditions.These findings may have important implications for understanding the immune clearance of HBV in HBeAg-positive CHB patients.     

替比夫定与恩替卡韦治疗HBeAg阳性慢性乙型肝炎4年随访观察

目的比较替比夫定(LdT)和恩替卡韦(ETV)治疗HBeAg阳性的CHB,哪一个能较早地实现有限疗程。方法 60例HBeAg阳性的CHB患者随机分为LdT组和ETV组。在服药后第12周、24周及以后每24周复查,直至治疗和随访结束(4年,192周),检测血清HBV DNA定量、HBV血清标志物、肝功能、血清肌酸激酶。观察两组192周治疗结束时应答率及持续应答率以及患者达到停药标准所需的时间及费用。结果 192周时LdT组和ETV组治疗结束时应答率及持续应答率为43.3%(13/30)vs 16.7%(5/30)、36.7%(11/30)vs 10.0%(3/30),差异有统计学意义(P<0.05)。达到停药标准LdT组平均治疗时间为167.2周,费用28 089.6元,而ETV组平均治疗时间为186.4周,费用50 887.2元。结论治疗HBeAg阳性的CHB患者,实现有限疗程LdT更具有优势。     

替比夫定治疗HBeAg阳性慢性乙型肝炎48周疗效评估

目的探讨HBeAg阳性慢性乙型肝炎初治患者服用替比夫定的近期疗效。方法给予48例HBeAg阳性慢性乙型肝炎初治患者口服替比夫定治疗48周,观察患者应答情况。结果在治疗12周、24周和48周时,患者血清学应答率分别为22.9%、56.2%和64.6%,它们与基线ALT、AST和HBV DNA水平无相关;12周、24周、48周病毒学应答率分别为47.9%、85.4%、89.6%,与基线ALT、AST、HBV DNA水平无相关性(P>0.05),48周病毒学应答率高低与24周呈正相关(P<0.01);12周、24周、48周生化学应答率分别为47.9%、83.3%、95.8%,24周生化学应答发生与否与基线ALT、AST水平有相关性,发生生化学应答者治疗前ALT和AST水平明显高于未发生生化学应答者(P<0.05)。本组患者中有3例发生无肌肉症状的磷酸肌酸激酶升高(192～610U/L)。结论替比夫定治疗HBeAg阳性慢性乙型肝炎48周疗效满意,耐受性较好。     

Effects of telbivudine and entecavir for HBeAg-positive chronic hepatitis B: A meta-analysis

AIM: To compare the effects of telbivudine (LDT) and entecavir (ETV) in treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B by meta-analysis.METHODS: We conducted a literature search using PubMed, MEDLINE, EMBASE, the China National Knowledge Infrastructure, the VIP database, the Wanfang database and the Cochrane Controlled Trial Register for all relevant articles published before April 1, 2012. Randomized controlled trials (RCTs) comparing LDT with ETV for treatment of HBeAg-positive chronic hepatitis B were included. The data was analyzed with Review Manager Software 5.0. We used relative risk (RR) as an effect measure, and reported its 95% CI. Meta-analysis was performed using either a fixed-effect or random-effect model, based on the absence or presence of significant heterogeneity. Two reviewers assessed the risk of bias and extracted data independently and in duplicate. The analysis was executed using the main outcome parameters including hepatitis B virus (HBV) DNA undetectability, alanine aminotransferase (ALT) normalization, HBeAg loss, HBeAg seroconversion, drug-resistance, and adverse reactions. Meta-analysis of the included trials and subgroup analyses were conducted to examine the association between pre-specified characteristics with the therapeutic effects of the two agents.RESULTS: Thirteen eligible trials (3925 patients in total) were included and evaluated for methodological quality and heterogeneity. In various treatment durations of 4 wk, 8 wk, 12 wk, 24 wk, 36 wk, 48 wk, 52 wk, 60 wk and 72 wk, the rates of HBV DNA undetectability and ALT normalization in the two groups were similar, without statistical significance. At 4 wk and 8 wk of the treatment, no statistical differences were found in the rate of HBeAg loss between the two groups, while the rate in the LDT group was higher than in the ETV group at 12 wk, 24 wk, 48 wk and 52 wk, respectively (RR 2.28, 95% CI 1.16, 7.03, P = 0.02; RR 1.45, 95% CI 1.16, 1.82, P = 0.001; RR 1.45, 95% CI 1.11, 1.89, P = 0.006; and RR 1.86, 95% CI 1.04, 3.32, P = 0.04). At 4 wk, 8 wk, 60 wk and 72 wk of the treatment, there were no significant differences in the rate of HBeAg seroconversion between the two groups, while at 12 wk, 24 wk, 48 wk and 52 wk, the rate in the LDT group was higher than in the ETV group (RR 2.10, 95% CI 1.36, 3.24, P = 0.0008; RR 1.71, 95% CI 1.29, 2.28, P = 0.0002; RR 1.86, 95% CI 1.36, 2.54, P < 0.0001; and RR 1.87, 95% CI 1.21, 2.90, P = 0.005). The rate of drug-resistance was higher in the LDT group than in the ETV group (RR 3.76, 95% CI 1.28, 11.01, P = 0.02). In addition, no severe adverse drug reactions were observed in the two groups. And the rate of increased creatine kinase in the LDT group was higher than in the ETV group (RR 5.58, 95% CI 2.22, 13.98, P = 0.0002).CONCLUSION: LDT and ETV have similar virological and biomedical responses, and both are safe and well tolerated. However, LDT has better serological response and higher drug-resistance.     

替比夫定治疗妊娠慢性乙型肝炎2年临床观察

目的：探讨替比夫定（LDT）治疗妊娠合并慢性乙型肝炎的价值。方法采用前瞻性、单中心和非随机对照研究。选择慢性乙型肝炎患者40例,其中合并妊娠20例作为妊娠组,未合并妊娠20例作为无妊娠组。均经 LDT 600 mg/d治疗96周,检测治疗12、24、48和96周时 HBeAg、HBV DNA及 ALT的变化。孕产妇及新生儿健康评估与正常孕产妇对照。结果 LDT治疗96周后,妊娠组和无妊娠组 HBeAg血清学转换为5/14例和5/13例;HBV DNA〈500拷贝/mL分别占17/20例和14/19例;ALT 正常17/20例和14/19例;两组比较,差异无统计学意义（P〈0.05）。无妊娠组有2例病毒学突破（rtM204I突变）。妊娠组和无妊娠组各发生肌酸肌酶升高1例（325 U/L）和2例（273 U/L,412 U/L）。所有孕妇足月分娩,新生儿正常。结论 LDT用于妊娠慢性乙型肝炎疗效与非妊娠肝炎相同,未发现明显不安全因素。     

替比夫定治疗高ALT水平HBeAg阳性慢性乙型肝炎的临床观察

目的观察替比夫定治疗高ALT水平HBeAg阳性慢性乙型肝炎（CHB）患者的疗效。方法 60例HBeAg阳性的CHB患者以ALT为依据分为低ALT组（ALT在2倍ULN与10倍之间）和高ALT组（ALT在10倍ULN与20倍之间）,给予替比夫定600 mg/d,观察治疗52周时的应答情况。结果治疗52周时,高ALT组HBV DNA降低比例明显高于低ALT组,差异有统计学意义;低ALT组HBeAg阴转率及血清学转换率、HBsAg阴转率低于高ALT组,差异有统计学意义;高ALT组中有4例出现HBsAg阴转,3例出现了HBsAb;低ALT组中没有出现HBsAg阴转及血清学转换。52周时两组患者ALT复常率、病毒学反弹、对替比夫定耐药及肌酸激酶升高水平相似。结论高水平ALT是替比夫定治疗应答较好的预测因子     

血清HBsAg滴度监测对恩替卡韦治疗的HBeAg阳性慢性乙型肝炎患者应答反应的预测价值

目的探讨HBeAg阳性慢性乙型肝炎（CHB）患者血清HBsAg滴度的动态变化对恩替卡韦（ETV）治疗反应的预测价值。方法选择2011年1月～2012年1月在我肝病中心住院及门诊接受ETV（0.5mg/d）治疗的HBeAg阳性CHB患者78例,随访1年。于抗病毒治疗的0、3、6、9和12 m分别收集患者血清,采用化学发光法定量检测各时间点的HBsAg和HBeAg滴度;采用实时荧光定量PCR法检测血清HBV DNA载量;采用Pearson相关分析分析HBsAg与HBV DNA水平相关性,采用受试者工作特征曲线（ROC）预测患者的病毒学应答和确定最佳临界值。结果在78例患者中,69例（88.5%）患者发生病毒学应答（VR）,9例未发生病毒学应答;VR组患者基线ALT水平[（141.8±27.2）IU/ml]与未发生VR患者[（136.2±29.7）IU/ml]比,无统计学意义（t=0.27,P=0.793）;HBV DNA[（6.7±1.0）lg IU/ml]明显低于未发生VR患者[（7.6±0.8）lg IU/ml,t=-2.27,P=0.033];HBsAg滴度与未发生VR患者比,无统计学意义[（3.8±0.6）lg IU/ml对（4.0±0.4）lg IU/ml,t=-1.75,P=0.094）];HBsAg与HBV DNA水平呈正相关（r=0.45,P=0.02）;HBsAg在治疗开始的前3个月下降较快,3个月后下降较缓慢,从基线到治疗3个月时,VR组患者较未发生VR患者HBsAg下降更快[（0.3±0.2）lg IU/ml对（0.2±0.1）lg IU/ml,t=2.245,P=0.035）];在治疗3个月时,lg HBsAg滴度的ROC曲线下面积最大（AUC=0.840,P=0.005）,临界值为3.85 lg IU/ml的Youden指数最大（0.602）,其诊断敏感度为84.2%,特异度为78.7%。结论 ETV治疗3个月时lg HBsAg≤3.85 lg IU/ml可作为预测ETV治疗1年发生病毒学应答的指标。     

Lower baseline ALT cut-off values and HBV DNA levels better differentiate HBeAg（-） chronic hepatitis B patients from inactive chronic carriers

AIM： To determine whether new cut-off values for aianine aminotransferase （ALT） and baseline hepatitis B virus （HBV） DNA levels better differentiate HBeAg（-） chronic hepatitis B （CriB） patients from inactive chronic carriers.
METHODS： Ninety-one patients [32 HBeAg（＋） CriB, 19 inactive carriers and 40 HBeAg（-） CriB] were followed up for 2 years and were tested for HBV DNA levels by a PCR-based assay. ALT was tested twice during the last 6 mo using new cut-off values： ULN （upper limit of normal） 30 IU/L for males, 19 IU/L for females. Diagnostic accuracy, sensitivity, specificity, positive and negative predictive values were calculated by discriminant analysis.
RESULTS： When using the revised ALT cut-off values, the lowest optimal HBV DNA level that differentiated HBeAg（-） CHB patients from inactive carriers was 50000 copies/mL. The diagnostic accuracy of HBV DNA to determine inactive carriers with a cut-off of 50000 copies/mL was similar to the previously recommended cut-off of 100000 copies/mL （91%）. HBV DNA levels were lower than the cut-off value in 95% of inactive carriers and in 28% of HBeAg（-） CHB patients. With ALT 〈 30 IU/L in men and 〈 19 IU/L in women and HBV DNA levels 〈 100000 copies/mL, the risk of CHB is 5%. On the other hand, if ALT values were 〉 30 IU in men and 〉 19 IU in women and baseline HBV DNA levels were 〉 100000 copies/mL, the risk is 86%.
CONCLUSION： New cut-off values for ALT together with HBV DNA levels proposed by AASLD （American Association for the Study of Liver Diseases） and NIH （National Institute of Health） consensus seem appropriate to characterize inactive carriers.     

替比夫定治疗慢性乙型肝炎疗效的系统评价

目的:系统评价替比夫定(LDT)治疗慢性乙型肝炎(CHB)的治疗效果.方法:应用Cochrane系统评价方法计算机检索Cochrane Library(2009年第3期)、PubMed(1966-2009.9)、EMBASE(1974-2009.9)、中国生物医学数据库(CBM,1978-2009.9)、中国期刊全文数据库(CNKI,1979-2009.9)和维普数据库(VIP,1989-2009.9),同时在临床试验注册网站及Google搜索引擎进行检索,并追查纳入研究参考文献,收集以LDT治疗CHB的所有随机对照试验(RCT)和交叉试验.根据Cochrane协作网推荐的风险评估工具进行风险偏倚评估,用RevMan5.0软件进行统计学分析.结果:最终纳入10个RCTs,共4037例患者.7篇LDT对比拉米夫定(LAM)的研究结果显示,对于HBeAg阳性患者,LDT组较LAM组更有效提高血清HBVDNA检测不到率(RR=1.50,95%CI:1.38-1.64)、ALT复常率(RR=1.10,95%CI:1.05-1.16)、HBeAg转阴率(RR=1.23,95%CI:1.08-1.40)和HBeAg血清转...     

替比夫定治疗HBeAg阳性慢性乙型肝炎早期病毒学应答对疗效的预测价值

目的评价替比夫定治疗HBeAg阳性慢性乙型肝炎患者早期病毒学应答对疗效的影响。方法 82例HBeAg阳性慢性乙型肝炎患者接受替比夫定治疗52周,观察4周、12周和24周病毒学应答与不应答患者52周的疗效。结果在治疗52周时,82例患者ALT复常率、HBV DNA转阴率、HBeAg阴转率和HBeAg血清转换率分别为95.1%、95.1%、56.1%和32.9%;在治疗4周时HBV DNA转阴45例,未转阴37例。两组52周HBV DNA转阴率、ALT复常率、HBeAg阴转率和HBeAg血清转换率分别为100.0%对89.2%(P<0.05)、100.0%对89.2%(P<0.05)、64.4%对45.9%和37.8%对27.0%;在治疗12周时HBV DNA转阴67例,未转阴15例。两组52周HBV DNA转阴率、ALT复常率、HBeAg阴转率和HBeAg血清转换率分别为100.0%对73.3%(P<0.05)、100.0%对73.3%(P<0.05)、67.2%对6.7%(P<0.05)和40.3%对0.0%(P<0.05);在治疗24周时HBV DNA转阴78例,未转阴4例。两组52周HBV DNA转阴率、ALT复常率、HBeAg阴转率和HBeAg血清转换率分别为98.7%对25.0%(P<0.05)、98.7%对25.0%(P<0.05)、59.0%对0.0%(P<0.05)和34.6%对0.0%。结论替比夫定治疗HBeAg阳性慢性乙型肝炎患者早期病毒学应答对疗效有预测作用,早期对治疗应答的患者可以继续接受该治疗方案。     

替比夫定治疗HBeAgeAg阳性慢性乙型肝炎疗效的预测指标

目的探讨替比夫定治疗HBeAg阳性慢性乙型肝炎（CHB）48周的疗效及其预测指标。方法采用替比夫定（LdT）600 mg/d治疗78例HBeAg阳性CHB患者48周,从性别、年龄、ALT和HBV DNA基线、早期病毒学应答（治疗12周时HBV DNA转阴）为预测因素,分析其对治疗48周疗效的影响。结果性别、年龄与治疗8～48周时HBV DNA转阴无相关性（P〉0.05）;5 ULN≤ALT≤10 ULN组治疗24、36及48周时HBV DNA转阴率高于2 ULN≤ALT≤5 ULN组（P〈0.05,P〈0.01）;HBV DNA 106～105拷贝/ml组治疗48周时ALT复常率和HBV DNA转阴率高于HBV DNA〉107拷贝/ml组（P〈0.05）;早期病毒学应答组治疗48周时HBeAg阴转率ALT复常率和HBV DNA转阴率也高于非应答组（治疗12周时HBV DNA≥500拷贝/ml）（P〈0.05）。结论 ALT、HBV DNA基线、早期病毒学应答可能可以作为预测替比夫定抗HBV疗效的指标     

替比夫定与阿德福韦酯治疗HBeAg阳性慢性乙型肝炎的疗效观察

目的比较替比夫定与阿德福韦酯治疗HBeAg阳性慢性乙型肝炎的疗效和安全性。方法 175例HBeAg阳性慢性乙型肝炎患者被随机分为替比夫定组（85例）和阿德福韦酯组（90例）,比较两组在治疗后48周时的疗效。结果治疗后12周、24周、36周和48周时,替比夫定治疗患者HBV DNA水平低于阿德福韦酯组（P〈0.01）,HBV DNA转阴率和ALT复常率均高于阿德福韦酯组（P〈0.05或P〈0.01）;治疗后12周、24周和36周HBeAg转阴或血清学转换率和完全应答率也高于阿德福韦酯组（P〈0.05或P〈0.01）;治疗48周,替比夫定组有2例,阿德福韦酯组有1例出现病毒学反弹;两组均有良好的安全性。结论替比夫定较阿德福韦酯有更强的抑制HBV作用,其治疗可提高HBeAg转阴或血清学转换率和完全应答率。     

替比夫定治疗妊娠慢性乙型肝炎患者的疗效和安全性

替比夫定(LdT)作为妊娠B级抗病毒药物问世以来,对妊娠后期乙型肝炎病毒阻断宫内感染有效[1];但对妊娠慢性乙型肝炎(CHB)患者全程治疗的临床观察鲜有报告.本研究旨在通过从妊娠初至分娩后应用LáT治疗,观察其抗病毒疗效,预防肝衰竭,阻断宫内感染的安全性和有效性,以及探讨个体优化治疗方案.     

Efficacy of a Chinese herbal formula on hepatitis B e antigen-positive chronic hepatitis B patients

BACKGROUND No guideline recommends antiviral therapy for hepatitis B e antigen(HBe Ag)-positive chronic hepatitis B patients with persistently normal alanine aminotransferase levels and a high hepatitis B virus(HBV) DNA viral load.AIM To evaluate the feasibility and safety of a Chinese herbal formula as a therapeutic option for chronic HBV infection.METHODS In total,395 patients(30–65 years old) with confirmed HBe Ag-positive chronic hepatitis B infection and persistently normal alanine aminotransferase were randomized to receive either Chinese herbal formula or placebo for 96 wk.Endpoints to evaluate therapeutic efficacy included:(1) HBV DNA levels decreased to less than 4 log10 IU/m L at weeks 48 and 96;and(2) HBe Ag clearance and seroconversion rates at weeks 48 and 96.RESULTS HBV DNA levels ≤ 4 log10 IU/m L were 10.05% at week 48 and 18.59% at week 96 in the treatment group.The HBe Ag clearance and conversion rates were 8.54% and 8.04% at week 48 and 16.08% and 14.57% at week 96,respectively.However,HBV DNA levels ≤ 4 log10 IU/m L were 2.55% and 2.55% at weeks 48 and 96,respectively,and the HBe Ag clearance rates were 3.06% and 5.61% at weeks 48 and 96,respectively,in the control group.The quantitative hepatitis B surface antigen and HBe Ag levels at baseline and changes during the treatment period as well as the alanine aminotransferase elevation at weeks 12 and 24 were strong predictors of HBe Ag clearance.CONCLUSION High rates of HBV DNA reduction,HBe Ag clearance and seroconversion could be achieved with Chinese herbal formula treatments,and the treatments were relatively safe for HBe Ag-positive chronic hepatitis B-infected patients with persistently normal alanine aminotransferase.The ability of the compound to modulate host immune function probably contributed to this effect.     

Significant hepatic histopathology in chronic hepatitis B patients with serum ALT less than twice ULN and high HBV-DNA levels in Indonesia

OBJECTIVE: To study the prevalence of significant hepatic histopathology in chronic hepatitis B (CHB) patients with alanine aminotransferase (ALT) ≤ twice upper limit of normal (ULN) and its association with age, HBeAg status, hepatitis B virus (HBV)‐DNA level and viral genotype. METHODS: A prospective study was conducted over a 3‐year period in treatment‐naive CHB patients with ALT ≤ twice ULN. Patients with a history of acute flare hepatitis, use of alcohol and hepatotoxic drugs, hepatitis C, hepatitis D and human immunodeficiency virus (HIV) co‐infection were excluded from the study. Hepatic histopathology was assessed according to the METAVIR scoring system. RESULTS: A total of 145 patients were recruited, 81 (55.9%) of whom were male. The patients’ mean age was 41.50 ± 10.74 years (range 16–70 years). Significant hepatic inflammation was found in 59.3% of these patients, and significant hepatic fibrosis was found in 62.1%, the latter being associated with hepatitis B e antigen status, ALT levels and serum HBV‐DNA, but not with their age group or viral genotype. Significant hepatic fibrosis was found in 24 of 35 CHB patients (68.6%) who were previously considered in an immunotolerance phase. CONCLUSIONS The prevalence of significant hepatic histopathology in CHB patients with serum ALT levels ≤ twice ULN is high. Delayed antiviral treatment can be harmful.     

替比夫定与恩替卡韦治疗e抗原阳性慢性乙型肝炎的近期疗效比较

目的 观察替比夫定与恩替卡韦治疗HBeAg阳性慢性乙型肝炎患者近期疗效及安全性. 方法 80例患者随机分为替比夫定治疗组和恩替卡韦治疗组,分别在治疗前,治疗第12周和24周检测患者血清HBV DNA水平、ALT复常率、HBeAg阴转率和HBeAg/抗-HBe转换率,并比较不同基线血清HBV DNA水平患者治疗12周和24周时的血清HBV DNA下降值,HBV DNA低于检测值率,HBV DNA＜104拷贝/ml患者的比例.观察治疗过程中药物使用的安全性.结果 替比夫定和恩替卡韦组患者的基础人口学、临床和病毒学特征均具有可比性.治疗12周时,替比夫定组和恩替卡韦组患者HBV DNA低于检测值率均为50.0%,ALT复常率分别为52.5%和60.0%(P＞0.05),HBeAg阴转率分别为30.0%和5.0%(P＜0.01),HBeAg血清学转换率分别为20.0%和5.0%(P＜0.05);在治疗24周时,两组HBV DNA低于检测值率分别为80%和70%,(P＞0.05),ALT复常率分别为77.5%和75.0%(P＞0.05),HBeAg阴转率分别为45.0%和32.5%(P＞0.05),HBeAg血清学转换率分别为27.5%和17.5%(P＞0.05),两组均未发现明显不良反应.结论 替比夫定与恩替卡韦治疗HBeAg阳性的慢性乙型肝炎的近期HBV DNA水平低于检测值率,ALT复常率无明显差异;12周时替比夫定HBeAg血清学转换率高于思替卡韦组,但24周时两组间差异无统计学意义.     

替比夫定治疗HBeAg阳性慢性乙型肝炎疗效观察

比较替比夫定和阿德福韦酯治疗慢性乙型肝炎患者的疗效和安全性。方法选取我院2008年10月～2010年1月诊治的HBeAg阳性慢性乙型肝炎患者82例,随机分为治疗组42例,给予替比夫定600 mg/d和对照组40例,给予阿德福韦酯10 mg/d。观察治疗48 w。结果在治疗24周时,治疗组HBV DNA阴转率为69.04%,HBeAg阴转率为23.8%,对照组HBV DNA阴转率为25.0%,未发生HBeAg阴转情况（P＜0.01）;在治疗48 w时,治疗组HBV DNA阴转率为85.7%、血清HBeAg阴转率为28.6%、血清HBeAg转换率为11.9%,前两项指标均显著高于对照组（分别为25.0%、2.5%,P＜0.01和0%）;治疗组和对照组ALT复常率存在明显差异,分别为95.2%和82.5%（P＜0.01）。结论与阿德福韦酯比,替比夫定治疗HBeAg阳性慢性乙型肝炎,具有抑制病毒复制能力更强、血清HBeAg阴转率更高的特点。     

替比夫定治疗慢性乙型肝炎患者肌酸激酶增高现象分析

目的研究替比夫定(LdT)治疗慢性乙型肝炎(CHB)患者的肌酸激酶(CK)增高情况、增高后的处理及危险因素,评估LdT使用的安全性。方法纳入LdT治疗CHB患者527例,其中联合阿德福韦酯(ADV)91例、LdT单独治疗436例。合并慢性肾脏病(CKD)19例,孕妇58例。观察CK动态变化,肌肉症状,基线及观察结束时病毒、免疫、生化学指标等。结果 321例患者出现CK升高,1~2级增高281例,3~4级增高40例,发生肌炎14例。CK3~4级增高后换药与不换药组CK下降差异无统计学意义(P=0.16)。男性是CK增高的危险因素(P0.01),妊娠与CKD为保护因素(P0.01;P=0.003)。结论 LdT抗病毒治疗过程中出现CK增高是普遍现象(孕妇及合并CKD患者除外),加强监测能提高LdT应用的安全性。     

阿德福韦酯片治疗E抗原阳性的慢性乙型肝炎临床观察

目的评价国产阿德福韦酯(ADV)片治疗HBeAg阳性慢性乙型肝炎患者的安全性与效果。方法采用随机对照方法,观察131例HBeAg阳性慢性乙型肝炎患者经口服阿德福韦酯片10mg/d,和口服苦参素胶囊0.6g/d,48周治疗期间和治疗后,血清HBADNA阴转率、ALT复常率、HBeAg阴转率,抗-HBe阳转率及不良反应。结果实验组血清HBVDNA阴转率、ALT复常率、HBeAg阴转率、抗-HBe阳转率均高于对照组,分别为53.2%/7.8%、36.0%/8.7%、13.6%/3.1%、6.2%/0(χ2值分别为56.32,23.18,P0.01;四格表确切概率法检验,P0.01)。实验组和对照组则分别为78.0%/9.6%、56.8%/28.7%、32.1%/11.7%、18.7%/6.3%(χ2值分别为76.78、21.72、20.61、21.32,P0.01)。结论国产阿德福韦酯片治疗HBeAg阳性慢性乙型肝炎的安全性及有效性均明显优于苦参素对照组。     

拉米夫定治疗慢性乙型肝炎出现血清转换的持续性研究

目的观察拉米夫定治疗慢性乙型肝炎患者5年的血清转换率和持续血清转换率及多元因素对两者的影响。方法81例慢性乙型肝炎患者,每天服用拉米夫定100 mg,持续5年。出现血清转换后, 继续服拉米夫定6个月以上(每3个月随访1次,至少2次以上),仍为乙型肝炎e抗原(-)和抗-HBe( ), 则停药并继续随访6-12个月。所需观察项目有丙氨酸氨基转移酶、血清病毒学标志物、乙型肝炎病毒DNA 载量及基因分型、YMDD变异等。结果(1)共有26例患者出现血清转换。总血清转换率为32.10% (26/81)。第1-5年,每年累积的血清转换率为16.05%、19.75%、27.16%、28.40%和32.10%。(2)停药后4例出现复发,持续血清转换率为84.62%(22/26)。(3)经Logistic多元回归分析,得出近期血清转换率和持续血清转换率与治疗前丙氨酸氨基转移酶水平呈正相关,与治疗前乙型肝炎病毒DNA水平呈负相关。持续血清转换与血清转换后继续服药时间有相关性。结论慢性乙型肝炎患者出现血清转换后继续应用拉米夫定治疗6个月以上,大多数患者可达到持续转换。对持续血清转换的影响因素为治疗前丙氨酸氨基转移酶和乙型肝炎病毒DNA水平(P<0.05)。