Objective To evaluate the effectiveness and safety of different doses of interferon alfa (INF-α) in the treatment of chronic hepatitis C (CHC). Methods Such databases as MEDLINE, EMbase, CENTRAL, CBM, CNKI, VIP and WanFang Data were searched to collect the randomized controlled trials (RCTs) on different doses of INF-α in the treatment of CHC published before August, 2012. According to the inclusion and exclusion criteria, two reviewers independently screened literature, extracted data and evaluated the quality of the included studies, and then meta-analysis was performed using RevMan 5.0 software. Results A total of 13 RCTs involving 1 442 patients were included. The results of meta-analysis on different doses of INF-α showed that, a) There was no significant difference in the complete response rate between the 3 MU dose group and the 1 MU dose group (RR=0.83, 95%CI 0.52 to 1.32, P=0.43), but there was significant difference in the sustained response rate between those 2 groups (RR=1.89, 95%CI 1.00 to 3.59, P=0.05); and b) No significant differences were found in the complete response rate among the 3 MU dose group, the 6 MU dose group, and the 1 MU dose group. Conclusion INF-α in dose of 3 MU, 3 times daily, is effective in treating CHC, but it would not rule out that higher dose takes more effective action. When INF-α is used to treat CHC, an individualized medication should be applied according to patients’ tolerance and economic status.
Objective To assess the efficacy of telbivudine in the treatment of chronic hepatitis B (CHB). Methods Randomized controlled trials (RCTs) of telbivudine therapy vs. lamivudine therapy in both Chinese and English were retrieved from seven electronic databases with a cut-off date in February 2010, including PubMed, EMbase, VIP, CBM, CNKI, and The Cochrane library. The meta-analyses and evaluation on methodology quality were performed for the included studies. Results Two RCTs as Grade-A study were included. The meta-analyses showed that telbivudine was superior to lamivudine in aspects of therapeutic response (RR=1.28, 95%CI 1.10 to 1.48, P=0.001), ALT normalization (RR=1.12, 95%CI 1.01 to 1.23, P=0.02), and PCR-negative HBV DNA or below the lower limit (RR=1.44, 95%CI 1.36 to 1.53, Plt;0.000 01), primary treatment failure (OR=0.28, 95%CI 0.18, to 0.43, Plt;0.000 01), viral breakthrough (OR=0.38, 95%CI 0.32 to 0.47, Plt;0.000 01) and viral resistance (OR=0.44, 95%CI 0.36 to 0.55, Plt;0.000 01). Conclusion Based on the current clinical evidence, telbivudine demonstrates superiority in comparison with lamivudine on all direct measures of antiviral efficacy for CHB. Because of the short follow-up duration and the small sample size of the included studies, it is expected to further discuss the long-term efficacy.
Objective To investigate the current situation of randomized controlled trials or clinical controlled trial (RCT/CCT) on chronic hepatitis B and whether to offer reliable evidence for clinical practice in China. Methods RCT/CCT identified from six Chinese clinical journals were searched manually and assessed according to international standard of evidence-based medicine. Results 308 issues containing 212 therapeutic articles and 88 RCT/CCT on chronic hepatitis B were identified and analyzed. Conclusion the quantity and quality of RCT/CCT of chronic hepatitis B did not meet the need of clinical practice.
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.
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 evaluate the effectiveness and safety of Gansu for chronic hepatitis B. Methods We searched The Cochrane Central Register of Controlled Trials (CCTR), PubMed, EMbase, CBM, CNKI, VIP, and Wanfang databases up to Dce. 2009. The methodological quality assessment and data extraction of the included studies were conducted by two reviewers independently according to the inclusion and exclusion criteria. Meta-analyses were performed for homogeneous studies using RevMan 4.2.10 software. Results A total of 14 studies involving 1 755 patients met the inclusion criteria. Of which, 12 studies did not report randomization method, and the other two studies reported inadequate methods of randomization. None of the studies enforced allocation concealment and performed blinding. We conducted subgroup analyses based on the outcome measures and interventions. The results of meta-analyses showed: (1) In terms of reducing ALT, Gansu + conventional therapy was superior to conventional therapy alone. (2) In terms of the HBsAg seroconversion rate, no significant difference was found between the two groups. (3) In terms of the HBeAg, no significant difference was found between the two groups at 3 months’ follow-up. (4) In terms of the HBV-DNA, Gansu + conventional therapy was superior to conventional therapy alone at 3 and 6 months’ follow-up, but theses differences were not found between Gansu + Lamivudine/ Adefovir and Lamivudine/ Adefovir alone. In terms of reducing the index of hepatic fibrosis, Gansu + conventional therapy was superior to conventional therapy alone. Conclusion Gansu might be effective in normalizing ALT levels, clearing HBV DNA, achieving virus seroconversion and improving hepatic fibrosis, without any serious adverse effects. However, because the overall effects cannot be pooled for analysis, more evidence is needed to support this finding.
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.
Objective To evaluate the effectiveness and safety of kushenin for chronic hepatitis B. Methods We searched The Cochrane Hepato-Bil iary Group Controlled Trials Register (March, 2006), The Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 1, 2006), MEDLINE (1966 to present), EMBASE (1966 to present), OVID (1965 to present), the Chinese Biomedical Database (CBM) (1978 to 2006) and CNKI. Qual ity assessment and data extraction were conducted by two reviewers independently, and disagreement, if any, was resolved by discussion. Meta-analyses were performed for homogeneous studies. Results A total of 56 studies involving 5156 patients met the inclusion criteria. These included 3 randomized controlled trials (RCTs), 7 quasi-RCTs, and 46 other studies that did not report randomization methods. None of the trials enforced allocation concealment and only one trial performed blinding.We conducted subgroup analyses based on the outcome measures and interventions. Compared with interferon,the HBeAg seroconversion rate at 12 months after treatment was lower in patients treated with kushenin (RR=0.72, 95%CI 0.58 to 0.90); compared with lamivudine, a lower HBV DNA seroconversion rate after 12 and 24 weeks of treatment was associated with kushenin (RR=0.48, 95%CI 0.33 to 0.70; RR=0.40, 95%CI 0.26 to 0.63). No significant differences were noted between the kushenin group and the control group for all the other outcome measures. Conclusion Kushenin might be effective in normal izing ALT levels, clearing HBV DNA, achieving virus seroconversion and improving hepatic fibrosis, without any serious adverse effects. However, because the overall effects cannot be pooled for analysis, more evidence is needed to support this finding.
Objective To evaluate the effectiveness and safety of treatment with Fuzheng Huayu capsule for liver fibrosis of chronic hepatitis B (CHB). Methods We searched MEDLINE, EMBASE, Cochrane Database of Controlled Trials (CCTR), CBMweb and CNKI up to March 2008. The references of retrieved literature were also hand searched. Randomized controlled trials (RCTs) which compared Fuzheng Huayu capsule with placebo or other drugs were collected. Data extraction and quality assessment were performed by two reviewers independently. The Cochrane Collaboration’ s software RevMan 4.2.10 was used for data analyses. Results Seven RCTs involving 590 cases of liver fibrosis of CHB were included. As for their methodological quality, one was graded A, one was graded B and the others were graded C. We carried out subgroup analyses based on treatment course and intervention measures. In terms of reducing haluronic acid, Fuzheng Huayu capsule was more effective than Huoluo Shugan capsule when the treatment course was 3 months (WMD=–61.75, 95%CI –105.20 to –18.30); significant differences were also noted between Fuzheng Huayu capsule and placebo (WMD=–187.72, 95%CI –244.23 to –31.21) or Huoluo Shugan capsule (WMD=–120.03, 95%CI –158.41 to –81.65) when the treatment course was 6 months. In terms of reducing IV-C, Fuzheng Huayu capsule was more effective than Gantaile when the treatment course was 6 months (WMD=–72.32, 95%CI –84.30 to –60.34). As for improving liver fibrosis at stage S, significant differences were observed between Fuzheng Huayu capsule and Gantaile (RR=2.33, 95%CI 1.37 to 3.96) or Huoluo Shugan capsule (RR=1.30, 95%CI 1.03 to 1.65). Except a very small number of gastrointestinal reactions, no significant adverse reactions were reported. Conclusion Fuzheng Huayu capsule is effective in reducing haluronic acid and improving liver fibrosis at stage S, especially when the treatment course is prolonged from 3 months to 6 months. No significant adverse reactions are reported. Because most of the included trials are of poor quality and small sample size, more high-quality RCTs are needed.
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.