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.
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 efficacy and safety of genus Phyllanthus for chronic HBV infection. Design a systematic review of randomized clinical trials. Methods Randomized trials comparing genus Phyllanthus versus placebo, no intervention, general non-specific treatment, other herbal medicine, or interferon treatment for chronic HBV infection were identified by electronic and manual searches. Trials of Phyllanthus herb plus interferon versus interferon alone were also included. No blinding and language limitations were applied. The methodological quality of trials was assesses, by the Jadadscale plus allocation concealment. Results Twenty-two randomized trials (n=1 947) were identified. The methodological quality was high in five double blind trials and rest was low. The combined results showed that Phyllanthus species had positive effect on clearance of serum HBsAg (relative risk 5.64, 95%C1 1.85 to 17.21) compared with placebo or no intervention. There was no significant difference on clearance of serum HBsAg, HBeAg and HBV DNA between Phyllanthus and interferon. Phyllanthus species were better than non-specific treatment or other herbal medicines on clearance of serum HBeAg, HBeAg, HBV DNA, and liver enzyme normalization. Analyses showed a better effect of the Phyllanthus plus interferon combination on clearance of serum (1.56, 1.06 to 2.32) and HBV DNA (1.52, 1.05 to 2.21) than interferon alone. No serious adverse events were reported. Conclusions Based on the review Phyllanthus species may have positive effect on antiviral activity and liver biochemistry in chronic HBV infection. However, the evidence is not b due to the general low methodological quality and the variations of the herb. Further large trials are needed.
Objective To compare adefovir monotherapy with adefovir-thymosin alpha-1 combination therapy for chronic hepatitis B. Methods We searched The Cochrane Library, MEDLINE, PubMed, the Chinese Biomedical Database (CBM), CNKI, Wanfang, and VIP databases up to February 2010 to identify randomized controlled trials (RCTs) comparing adefovir plus thymosin alpha-1 versus adefovir alone for chronic hepatitis B. We also scanned references of all included studies and pertinent reviews. The methodological quality assessment and data extraction were conducted by two reviewers independently according to the Cochrane Reviewer’s Handbook 5.0.2 . Meta-analyses were performed using RevMan 5.0 software. Results Eleven trials involving 895 patients were included. The results of meta-analyses shoued: the HBeAg seroconversion rate of the combination therapy group was higher than that of the monotherapy group, both at the sixth month and the twelfth month (RR=1.77, 95%CI 1.38 to 2.27; RR=1.74, 95%CI 1.44 to 2.10); and there were also significant differences between the two groups for secondary outcomes including HBV-DNA negative, ALT normalization, etc.Conclusion Adefovir-thymosin alpha-1 combination therapy might be more effective than adefovir monotherapy for chronic hepatitis B. Significant differences are even observed at the sixth month. However, the results should be interpreted with caution because of the low quality of the included studies. High-quality, large-scale RCTs are needed to further prove the results.
Objective To explore the relationship between the level of serum ferritin (SF) and liver damage in patients with chronic hepatitis B (CHB). Methods The concentration of serum ferritin of 98 patients with CHB from July to October 2014 was measured, and then correlation analysis was performed to analyze the correlation between SF and such indexes as serum tumor marker α-fetoprotein, biochemical markers [alanine amino transferase (ALT), aspartate amino transferase (AST), total protein (TP), albumin and total bilirubin (TBIL)], and hepatitis B serum markers (hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B e antigen, hepatitis B e antibody, and hepatitis B core antigen). Serum hepatitis B virus DNA (HBV-DNA) viral load was also tested, and then the discrepancy of SF levels in the high and low viral load groups was analyzed. Results The average concentration of the abnormally elevated SF was (878.69±837.98) ng/mL. The SF mean difference between low-load HBV-DNA and high-load HBV-DNA was statistically significant (P < 0.05). Serum ferritin levels were independently and positively correlated with ALT, AST, and TBIL (P < 0.01) and inversely correlated with TP and albumin (P < 0.01). Conclusion The rise of SF is associated with liver damage, which can reflect the state of inflammation of patients with CHB.
目的 评估替比夫定与阿德福韦酯联合治疗优化阿德福韦酯单药治疗应答不佳的阳性慢性乙型肝炎患者的疗效。 方法 选择2008年6月－2009年8月间共26例阿德福韦酯治疗至少12个月且病毒学应答不佳的乙型肝炎病毒e抗原（HBeAg），阳性的慢性乙型肝炎患者，在10 mg阿德福韦酯治疗的基础上，加用600 mg替比夫定。肝功能和乙型肝炎病毒（HBV） DNA每3个月评估1次，乙型肝炎两对半和腹部B型超声每半年评估1次。 结果 在第1年的治疗期间，所有患者血清HBV DNA水平均呈进行性下降，其中24例（92.3%）血清HBV DNA水平在联合治疗12个月时低于检测值下限，有25例（96.2%）患者丙氨酸转氨酶水平复常。治疗6个月时，分别有7例（26.9%）和2例（7.7%）患者发生HBeAg消失和血清学转换；治疗12个月时，分别有11例（42.3%）和8例（30.8%）患者发生HBeAg消失和血清学转换。整个治疗期间，26例患者均未出现病毒学突破。 结论 阿德福韦酯单药治疗应答不佳时，加用替比夫定可有效控制病毒，使患者获得较好的病毒学、生化学和免疫学应答。Objective To evaluate the curative efficacy of telbivudine combined with defovir dipivoxil on positive-HBeAg chronic hepatitis B patients with suboptimal response to adefovir dipivoxil. Methods A total of 26 HBeAg-positive patients with suboptimal response to adefovir dipivoxil (treated with adefovir dipivoxil for more than 12 months) were treated with adefovir dipivoxil 10 mg in addition to telbivudine 600 mg between June 2008 and August 2009. Liver function and serum hepatitis B virus (HBV) DNA tests were assessed at the baseline and 3-month intervals, whereas HBV serological markers and abdominal ultrasonography were carried out every 6 months. Results During the first year of treatment, all patients showed a progressive decline of serum HBV DNA levels; while undetectable serum HBV DNA and normalization of alanine aminotransferase was achieved in 24(92.3%) and 25 (96.2%) patients, respectively, at the end of the first year of treatment. The 6- and 12-month cumulative rates of HBeAg loss were 26.9% (7/26) and 42.3% (11/26), respectively; and corresponding cumulative rates of HBeAg/anti-HBe seroconversion were 7.7% (2/26) and 30.8 (8/26), respectively. During the observation period, no virological breakthrough was detected. Conclusion Telbivudine combined with defovir dipivoxil may be a good choice for patients with suboptimal response to adefovir dipivoxil, which could induce effective viral inhibition and help patients obtain more virological, biochemical and immunological responses.
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.
ObjectiveTo systematically review the efficacy of lamivudine (LAM) plus adefovir (ADV) versus entecavir (ETV) monotherapy for LAM-resistant chronic hepatitis B patients. MethodsWe electronically searched databases including PubMed, The Cochrane Library (Issue 12, 2013), CBM, CNKI, VIP, WanFang Data from their inception to December 2013, to collect randomized controlled trials (RCTs) or cohort studies of LAM+ADV versus ETV for LAM-resistant chronic hepatitis B. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data and assessed the methodological quality of included studies. Then, meta-analysis was performed using RevMan 5.2 software. ResultsA total of 13 RCTs and 5 cohort studies involving 1 336 patients were included. The results of meta-analyses of RCTs showed that:there were no significant differences between the LAM+ADV group and the ETV group in the negative rates of serum HBV-DNA (RR=1.00, 95%CI 0.91 to 1.10, P=0.94), HBeAg (RR=0.90, 95%CI 0.70 to 1.17, P=0.43), serum ALT recovery rate (RR=0.97, 95%CI 0.90 to 1.05, P=0.45) and serum HBeAg conversion rate (RR=0.71, 95%CI 0.40 to 1.24, P=0.22) at the 48th week. The results of meta-analyses of cohort studies showed that:there were no significant differences between the two groups in the negative rates of serum HBV-DNA (RR=1.37, 95% CI 0.91 to 2.06, P=0.13) and serum ALT recovery rate (RR=0.99, 95%CI 0.87 to 1.12, P=0.87), but the ETV group had higher serum HBeAg conversion rate (RR=0.24, 95% CI 0.07 to 0.79, P=0.02). ConclusionCurrent evidence shows that the efficacy of LAM+ADV is similar to ETV at the 48th week for LAM-resistant chronic hepatitis B patients. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.
ObjectiveTo analyze hepatitis B virus (HBV) genotype distribution and drug-resistant mutations in West China Hospital of Sichuan University, providing basis for hepatitis B individualized treatment.MethodsA total of 786 chronic hepatitis B patients admitted to West China Hospital of Sichuan University from January 2016 to December 2018 were enrolled in the study. Genotype and drug-resistant mutations were analyzed by Sanger sequencing, and statistical analysis was conducted by χ2 test.ResultsThree genotypes (B, C and D) were identified in 786 samples, 489 (62.2%) in genotype B, 291 (37.0%) in genotype C , and 6 (0.8%) in genotype D. The distribution differences of B and C genotypes in age and ethnic groups were statistically significant (P<0.05). Among them, 627 cases had drug-resistant mutations, with a drug-resistant mutation rate of 79.8%. A total of 262 cases (33.3%) were resistant to lamivudine and tibivudine, 102 cases (13.0%) were resistant to lamivudine, tibivudine and entecavir; 83 cases (10.6%) were resistant to adefovir dipivoxil. No tenofovir resistant strains were detected in 786 samples. There were statistically significant differences in drug resistance between B and C genotypes (χ2=14.356, P<0.01). The most common single mutation was M204I [179 cases (22.8%)], followed by 46 cases (5.9%) of A181V/T associated with adefovir dipivoxil resistance. The most common mixed mutation was L180M+M204V/I in 83 cases (10.6%), and another 102 cases (13.0%) showed M250V and/or V173L and/or T184A/G/S/I and/or S202G/I with L180M+M204V/I.ConclusionsHBV genotypes in West China Hospital of Sichuan University are mainly B and C, and the situation of drug resistance is severe and the mutation pattern is complex. Therefore, detecting HBV genotype and drug resistance mutation is necessary, which may develop better clinical treatments.