目的:观察α干扰素治疗HBeAg(+)慢性乙型肝炎患者过程中病毒学及血清学动态变化情况,通过早期疗效预测终末疗效。方法:观察144例HBeAg(+)慢性乙型肝炎患者经α干扰素治疗24WK及随访24WK 过程中HBV-DNA以及HBeAg变化情况.结果:经α干扰素治疗12、24、48WK时,HBV-DNA下降到可检测值以下病例数分别为32、32、31例;同期HBeAg发生血清转换病例数分别为16、17、21例。结论:干扰素治疗12WK时患者病毒学及血清学结果可早期预测终末疗效。
【摘要】 目的 通过检测临床确诊为慢性乙型肝炎患者血清谷丙转氨酶（ALT）、谷草转氨酶（AST）、甲状腺激素T3、T4及促甲状腺素（TSH）含量，进一步探讨慢性乙型肝炎患者肝损情况与甲状腺分泌功能的关系。 方法 收集2009年1-4月79例确诊为慢性乙型肝炎患者（病例组）血清标本，分别检测其ALT、AST、甲状腺激素T3、T4及TSH含量。以同期健康体检者30例作为对照组。比较两组的差异及各指标间的相关性。 结果 病例组AST为（87±113） U/L、ALT为（135±241） U/L、AST/ALT为0.97±0.57、TSH为（1.63±1.29） mU/L、T3为（1.61±0.52）ng/mL、T4为（10.7±2.9） μg/dL，对照组分别为（23±5） U/L、 （18±5） U/L、1.31±0.26、（2.13±0.90） mU/L、（1.19±0.16） ng/mL和（8.6±0.9） μg/dL，两组各指标比较均有统计学差异（Plt;0.01）。所有指标均正常的共有6例（7.6%），有73例（92.4%）存在不同程度的指标异常；在68例AST/ALT比值降低的慢性乙型肝炎患者（93.2%）中，伴有单纯T4升高的有11例（16.2%），单纯T3升高的有4例（5.9%），T3、T4同时升高的有11例（16.2%），T3、T4同时升高且TSH降低的有2例（2.9%），1例T4升高且TSH降低（1.5%），1例仅TSH升高（1.5%）；在4例AST/ALT比值正常的慢性乙型肝炎患者（5.5%）中，有1例T3、T4同时升高且TSH降低，1例T3和T4同时升高，1例单纯T4升高，1例单纯TSH降低；有1例仅AST/ALT比值升高而其他项正常。 结论 慢性乙型肝炎患者除AST/ALT比值异常外，还同时伴有不同程度的甲状腺激素指标异常，其原因可能与慢性乙型肝炎应用干扰素治疗时甲状腺功能受损有关。【Abstract】 Objective To explore the relationship between liver damage and the secretion function of thyroid by detecting the serum alanine aminotransferase (ALT), aspartate aminotransferase(AST), T3, T4, and thyroid stimulating hormone (TSH) in patients with chronic hepatitis B. Methods The serum samples of 79 patients with chronic hepatitis B from January to April 2009 were collected, and the ALT, AST, T3, T4, and TSH concentrations were detected. Another 30 healthy subjects were selected as the control. The detected indexes were compared between the two groups. Results In the case group, the concentration of AST was (87±113)U/L, ALT was (135±241)U/L,AST/ALT was 0.97±0.57, TSH was (1.63±1.29) mU/L, T3 was (1.61±0.52) ng/mL, and T4 was (10.7±2.9) μg/dL; while in the control group, the concentrations of the items were (23±5) U/L, (18±5)U/L, 1.31±0.26, (2.13±0.90) mU/L, (1.19±0.16) ng/mL, and (8.6±0.9) μg/d L, respectively. The differences between the two groups were significant (Plt;0.01). Among the 79 case, 6 (7.6%) had a totally normal result, and 73(92.4%) had an abnormal result. There were 68 patients who had a low ratio of AST/ALT, among whom 11 (16.2%) had a simple T4 elevation, 4(5.9%) had a simple T3 elevation,11(16.2%) had an elevation of both T3 and T4, 2 (2.9%) had an elevation of both T3 and T4 and a depression of TSH, 1(1.5%) had an elevation of T4 and a depression of TSH, and 1 (1.5%) had a simple TSH elevation. There were 4 cases who had a normal ratio of AST/ALT, among whom 1 had an elevation of both T3 and T4 and a depression of TSH, 1 had an elevation of both T3 and T4, 1 had a simple T4 elevation, and 1 had a simple TSH depression. There was 1 case who had only an elevation of AST/ALT. Conclusion Most of the patients with chronic hepatitis B have an abnormal result of thyroid hormone together with the abnormal ratio of AST and ALT. The reason mainly lies in the damage of thyroid function by the usage of interferon for the therapy of chronic hepatitis B.
Objective To assess the efficacy between Peginterferon α-2a and common Interferon in HBeAg positive chronic hepatitis B. Methods MEDLINE, EBSCO, PubMed, CNKI, WangFang were searched from the beginning to May 2009, and the references of eligible studies were manually screened. Randomized controlled trials comparing Peginterferon-alpha2a with common interferon in HBeAg positive chronic hepatitis B were eligible for inclusion. Jadad score method was adopted to evaluate the methodological quality of included studies. Meta analysis was conducted by RevMan 5.0 software supplied by the Cochrane Collaboration. Subgroup analyses were used in treatment and observation course. Results Six randomized controlled trials were included (n=688). The treatment duration of 48 weeks and 24 weeks were reported in four and two studies, respectively. We carried out subgroup analysis according to treatment. Meta-analysis showed that Peginterferon-alpha2a (180 ug/d, 48 W) could significantly clear HBeAg, clear HBVDNA, normalize ALT and HBeAg seroconversion compared with common Interferon (Plt;0.05). Peginterferon-alpha2a (180 ug/d, 24 W) could effectively clear HBV DNA [P=0.04, RR=1.44, 95%CI (1.01, 2.05)], but was not effective in loss of HBeAg, HBeAg seroconversion and ALT normalization (Pgt;0.05). Conclusion The efficacy of 48 weeks treatment with Peginterferon α-2a is better than common Interferon. The efficacy of 24 weeks treatment with Peginterferon α-2a is only better in HBV-DNA negative rate than common Interferon. However, because the methodological quality of included studies is not high, this conclusion should be carefully considered in clinical use.
【摘要】 目的 分析慢性乙肝患者血清生化、血常规、血清病毒载量及乙型肝炎标志物与肝组织炎症分级、纤维化分期的相关性,以找到有较好相关性的临床指标；通过肝活检证实临床诊断与病理诊断的符合情况,探讨肝活检的重要性及价值。方法 对2007年6月—2009年8月在传染科行肝穿刺活检的359例慢性乙型肝炎患者的血清丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)、总胆红素(TB)、白蛋白(ALB)、球蛋白(GLB)等指标,白细胞(WBC)、血小板(PLT)等指标,凝血酶原时间(PT),血清HBV DNA定量及乙肝标志物的不同状态与肝穿病理分级、分期的相关性进行分析；统计慢性乙肝患者临床诊断与病理诊断的符合情况。结果 肝组织炎症分级及纤维化分期之间有一定相关性(Plt;0.05)；血清ALT、AST、ALB、GLB、PT有助于判断肝组织炎症程度(Plt;0.05)；ALB、GLB、WBC、PLT、PT对肝组织纤维化程度的评估有意义(Plt;0.05)；HBV DNA复制水平与肝组织炎症及纤维化无关(Pgt;0.05),但存在负相关的趋势；纤维化程度高的患者HBeAg阴性组较HBeAg阳性组更多(Plt;0.05)。慢性乙型肝炎患者临床与病理诊断总符合率为56.3％。结论 动态监测慢性乙肝患者肝功能、血常规、凝血常规在一定程度上有助于判断疾病的程度,但要确诊肝组织炎症分级及纤维化分期,肝组织病理活检是必需的。
Objective To compare the combination of Xiao Chai Hu Tang and interferon versus the simple interferon for the management of chronic hepatitis B (CHB) in terms of clinical therapeutic effect and safety. Methods Such databases as PubMed, CBM disc, CNKI, VIP, Japana Centra Revuo Medicina were searched to include the randomized control trials (RCTs) of treating chronic hepatitis B by using Xiao Chai Hu Tang plus interferon as the treatment group and the interferon as the control group. The quality of the inclusive methodology was evaluated by two reviewers independently. RevMan5.0.24 software was employed for meta-analyses. Results Seven RCTs involving 668 patients were included and all of them were classified as Grade C methodologically. The results of meta-analyses demonstrated: compared with the simple interferon treatment, adding Xiao Chai Hu Tang to interferon was able to significantly increase the HBV-DNA negative conversion ratio (RR=1.44, 95%CI 1.18 to 1.76, P=0.000 4) and the HBeAg negative conversion ratio (RR=1.54, 95%CI 1.21 to 1.94, P=0.000 4); when the intervention duration was more than 12 weeks, the ALT normalization rate was improved significantly (24 weeks: RR=1.39, 95%CI 1.17 to 1.66, P=0.000 2; 12 weeks: RR=1.79, 95%CI 1.23 to 2.61, P=0.002) and the incidence of flu-like symptoms induced by interferon was significantly reduced (liver-protection treatment: RR=0.54, 95%CI 0.40 to 0.73, Plt;0.000 1; Non-liver-protection treatment: RR=0.75, 95%CI 0.59 to 0.95, P=0.02). The funnel plot was asymmetric, indicating publication bias. Conclusion Although Xiao Chai Hu Tang maybe has certain potential supplementary benefits to interferon for the management of CHB. The results of the above meta-analyses should be interpreted prudently because there exit disparities in domestic and international trails with the shortage of double blind or multi-centered clinical trials with high quality. The current evidence provides no way to compare the combination of Xiao Chai Hu Tang plus interferon with the simple interferon for the treatment of CHB and no accurate conclusion in terms of clinical therapeutic effects and safety.
Objective To assess the efficacy of lamivudine in patients with HBeAg positive chronic hepatitis B.Methods MEDLINE, SCI, Current Content Connect, The Cochrane Library, and Chinese Biomedical Database were searched from the beginning to September 2005, and the references of eligible studies were manually screened. R.andomized controlled trials comparing lamivudine with non-antiviral interventions （ placebo, no treatment and standard care ） in patients with chronic hepatitis B were eligible for inclusion. Two investigators independently assessed the quality and extracted the data. Heterogeneity was examined by Chi-square test. Fixed and random effect meta-analysis were used to pool the data. Subgroup analyses were used in treatment course. Results Eleven R.CTs were included （ n = 1 237 ）. All reported the effect of lamivudine （100 mg/d） , and one of them included lamivudine （25 mg/d）. The treatment duration of 52 weeks and less than 26 weeks were reported in eight and three RCTs, respectively. Six RCTs adequately applied randomization, while other five RCTs were not reported in detail. Four RCTs adequately enforced allocation concealment, five RCTs enforced blinding bitterly. The others were not reported in detail. It was found by meta-analysis that, compared with the control, lamivudine （100 mg/d, 52 W） could significantly clear HBeAg [42.6% vs. 13% , RR 3.20, 95% CI （2.33, 4. 38）] and clearHBVDNA [71.78% vs. 20, 36%, RR3.42, 95%CI （2.80,4.19）], normalize ALT [65% vs. 34.9%, RR1.91, 95%CI （1.64,2.21）], achieve HBeAgseroconversion [16.1% vs. 7.29% , RR2.12, 95%CI （1.24,3.80） ] and histology response [57. 9% vs. 26.2%, RR 2. 17, 95% CI （ 1.67,2.81 ） ] ; Lanfivudine （100 mg/ d, 12 W） could effectively clear HBV DNA [ 50.7% vs 3.92% , RR 8.68, 95% CI （1.72,43.74 ） ] , but was not effective in loss of HBeAg, HBeAg seroconversion and normalization of ALT, Lamivudine （25 mg/d） could effectively clear HBV DNA [97.7% vs. 22.2% , RR 4.41, 95% CI （2.86,6.79） ] and improve histology response [59.3% vs. 30% , RR1.98, 95% CI （1.31,2.99 ） ], but was not effective in HBeAg seroconversion. Conclusions Lamivudine （100 mg/ d） is effective in clearing HBV DNA and HBeAg, normalizing ALT and achieving HBeAg seroconversion.
Objectives To conduct a meta-analysis to evaluate the efficacy and safety of thymosin-α1 for HBeAg-positive chronic hepatitis B. Methods We searched MEDLINE, Science Citation Index, Current Content Connect, Cochrane Controlled Trial Register and Chinese Biomedical Database (CBMdisc) to September 15, 2005, and screened the references of eligible trials by hand-searching. Randomized controlled trials (RCTs) comparing thymosin-α1 with non-antiviral interventions (placebo, no treatment and standard care) in patients with HBeAg positive chronic hepatitis B were eligible for inclusion. We conducted quality assessment and data extraction by two independent investigators with disagreement resolved by discussion. We used chi-square test and Galbraith plot to detect the heterogeneity, and used fixed (Mantel-Haenzel) and random effect model (DerSimonian-Laird) to pool the trials. When the results in two models differed, the results of random effect were reported. Subgroup analysis was performed to detect whether the duration affected the efficacy of thymosin. Results Four RCTs were included. It was found that the rate of loss of HBeAg was 38.8% in thymosin, significantly higher than that of 12.4% in control groups (RR 2.22, 95%CI 1.55 to 3.21, P=0.000). Loss of HBV-DNA was 36.9% in thymosin-α1, significantly higher than that of 13.8% in control groups (RR 2.18, 95%CI 1.50 to 3.17, P=0.000). Both short-duration (8-13 weeks) and regular duration (26-52 weeks) of thymosin-α1 achieved higher loss of HBeAg and HBV-DNA. The complete response rate was 32.3% in thymosin-α1, significantly higher than the control, 11.3% (RR 2.91, 95%CI 1.71 to 4.94, P=0.000). No statistical significance was found for HBeAg seroconversion and ALT normalization. No significant adverse drug reactions were found. Conclusions Thymosin-α1 might be efficacious in loss of HBeAg and HBV-DNA, and complete response for patients with HBeAg-positive chronic hepatitis B. Little evidence was available on HBeAg seroconversion, normalization of ALT, loss of HBsAg, and histological response. Further high-quality RCTs were needed for confirmation.
Objective To evaluate the effectiveness and safety of foscarnet sodium in the treatment of chronic hepatitis B. Methods We searched MEDLINE, EMbase, The Cochrane Library and CNKI from 1978 to June 2006. Randomized controlled trials of foscarnet sodium versus other drugs or no drugs in the treatment of chronic hepatitis B were identified. The quality of the included trials was evaluated by two reviewers independently. Meta-analysis was done using The Cochrane Collaboration’s RevMan 4.2.7. Results Seven studies (337 patients) were included; one compared foscarnet sodium versus interferon, and the other six compared foscarnet sodium versus no drugs. All the included studies were graded in terms of the quality of randomization, allocation concealment and blinding. All 7 studies were graded as level C. The meta-analysis showed that: ① foscarnet sodium was not significantly different from interferon in clinical efficacy, liver function, negative-conversion rate of virological markers and side effects. ② compared with the no drugs group, the negative-conversion rate of virological markers was significantly higher for the foscarnet sodium group, HBeAg (RR 6.20, 95%CI 1.76 to 21.79) and HBV-DNA (RR 4.13, 95%CI 1.32 to 12.86); but there were no significant differences in clinical efficacy, liver function and side effects. Conclusions Available evidence shows that: in the treatment of chronic hepatitis B the effectiveness and safety of foscarnet sodium are not significantly different from interferon, but only one trial is included in this review, so the evidence is weak. Compared with no drugs, foscarnet sodium significantly improves the negative-conversion rate of virological markers, but the evidence is insufficient to show whether foscarnet sodium could improve clinical efficacy and liver function, as well as reduce side effects.
ObjectivesTo systematically review the efficacy and safety of pegylated interferon α-2a (Peg-IFNα-2a) combined with entecavir (ETV) versus Peg-IFNα-2a alone in treatment of HBeAg-positive chronic hepatitis B (CHB) patients.MethodsThe Cochrane Library, PubMed, Web of Science, EMbase, CNKI, VIP and WanFang Data databases were electronically searched to collect randomized controlled trials (RCTs) on Peg-IFNα-2a combined with ETV for HBeAg-positive CHB from inception to March, 2019. Two reviewers independently screened literature, extracted data and assessed risk of bias of included studies. Then, meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 12 RCTs involving 1 130 patients were included. The results of meta-analysis showed that: compared with Peg-IFNα-2a monotherapy, Peg-IFNα-2a combined with ETV could improve the rate of serum HBV-DNA clearance (RR=2.55, 95%CI 1.83 to 3.55, P<0.000 01), ALT normalization (RR=2.37, 95%CI 1.76 to 3.20, P<0.000 01) and HBeAg seroconversion (RR=2.88, 95%CI 1.18 to 7.03, P=0.02) after 12 weeks of treatment. Additionally, it could improve the rate of serum HBV-DNA clearance (RR=2.10, 95%CI 1.74 to 2.53, P<0.000 01), AST normalization (RR=1.87, 95%CI 1.15 to 3.04, P=0.01), ALT normalization (RR=1.70, 95%CI 1.46 to 1.99, P<0.000 01), serum HBeAg clearance (RR=2.14, 95%CI 1.62 to 2.83, P<0.000 01), HBeAg seroconversion (RR=2.51, 95%CI 1.65 to 3.82, P<0.000 01) and serum HBsAg clearance (RR=2.78, 95%CI 1.06 to 7.31, P=0.04) after 24 weeks of treatment. It could also improve the rate of serum HBV-DNA clearance (RR=1.63, 95%CI 1.32 to 2.02, P<0.000 01), AST normalization (RR=2.75, 95%CI 1.82 to 4.16, P<0.000 01), ALT normalization (RR=1.47, 95%CI 1.33 to 1.63, P<0.000 01), serum HBeAg clearance (RR=1.65, 95%CI 1.42 to 1.91, P<0.000 01), HBeAg seroconversion (RR=1.91, 95%CI 1.51 to 2.41, P<0.000 01) and serum HBsAg clearance (RR=1.57, 95%CI 1.07 to 2.31, P=0.02) after 48 weeks of treatment. There was no statistically significance of adverse reactions in groups.ConclusionsCurrent evidence shows that Peg-IFNα-2a combined with ETV is superior to Peg-IFNα-2a monotherapy in the treatment of HBeAg-positive CHB, and does not increase the incidence of adverse reactions. Due to the limited quality and quantity of the included studies, more high quality studies are required to verify the above conclusion.