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 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 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.
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.
ObjectiveTo systematically review the diagnostic value of FibroScan for the staging of liver fibrosis in chronic hepatitis B. MethodsWe searched the PubMed, EMbase, Web of Knowledge, CBM, WanFang Data and CNKI databases for studies investigated the diagnostic value of FibroScan for hepatic fibrosis B from Jan. 1st, 2003 to Aug. 31st, 2013. Two reviewers independently screened literature according to the exclusion and inclusion criteria, extracted data and assessed methodological quality of included studies. Then, Stata 13.0 software was used to analyze the data. ResultsA total of 15 studies involving 2 588 patients were included. The results of meta-analysis showed that:the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and the AUC of SROC were 0.77 (95%CI 0.69 to 0.83), 0.84 (95%CI 0.70 to 0.87), 3.8 (95%CI 2.6 to 5.6), 0.29 (95%CI 0.22 to 0.38), 13 (95%CI 8 to 21), 0.82 (95%CI 0.82 to 0.88) for hepatic fibrosis; and were 0.81 (95%CI 0.73 to 0.87), 0.89 (95%CI 0.86 to 0.92), 7.5 (95%CI 5.3 to 10.3), 0.21 (95%CI 0.14 to 0.31), 36 (95%CI 20 to 65), 0.93 (95%CI 0.90 to 0.95) for early hepatic cirrhosis, respectively. ConclusionThe current evidence suggests that FibroScan is of good accuracy in the diagnosis of early hepatic fibrosis but not for hepatic cirrhosis in patient with chronic hepatitis B.
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.
This study aims to clarify host factors of IFN treatment in the treatment of chronic hepatitis B (CHB) patients by screening the differentially expressed genes of IFN pathway CHB patients with different response to interferon (IFN) therapy. Three cases were randomly selected in IFN-responding CHB patients (Rs), non-responding CHB patients (NRs) and healthy participants, respectively. The human type I IFN response RT2 profiler PCR array was used to detect the expression levels of IFN-related genes in peripheral blood monocytes (PBMCs) from healthy participants and CHB patients before and after Peg-IFN-α 2a treatment. The results showed that more differentially expressed genes appeared in Rs group than NRs group after IFN treatment. Comparing with healthy participants, IFNG, IL7R, IRF1, and IRF8 were downregulated in both Rs and NRs group before IFN treatment; CXCL10, IFIT1, and IFITM1 were upregulated in the Rs; IL13RA1 and IFI35 were upregulated in the NRs, while IFRD2, IL11RA, IL4R, IRF3, IRF4, PYHIN1, and ADAR were downregulated. The expression of IL15, IFI35 and IFI44 was downregulated by 4.09 (t = 10.58, P < 0.001), 5.59 (t = 3.37, P = 0.028) and 10.83 (t = 2.8, P = 0.049) fold in the Rs group compared with the NRs group, respectively. In conclusion, IFN-response-related gene array is able to evaluate IFN treatment response by detecting IFN-related genes levels in PBMC. High expression of CXCL10, IFIT1 and IFITM1 before treatment may suggest satisfied IFN efficacy, while high expression of IL13RA1, IL15, IFI35 and IFI44 molecules and low expression of IFRD2, IL11RA, IL4R, IRF3, IRF4, PYHIN1 and ADAR molecules may be associated with poor IFN efficacy.
ObjectiveTo observe the impact of antiviral therapy on prognosis in patients after curative resection for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). MethodsThe data of 50 patients who had undergone liver resection for HBV-related HCC in our department from August 2008 to June 2012 were retrospectively analyzed. The patients were divided into two groups:21 patients who had not antiviral therapy (untreated group) and 29 patients who received antiviral therapy using nucleotide analogues (antiviral therapy group). ResultsAfter radical resection of HCC, the disease-free survival rate of 1-year, 3-year, and 5-year were 72.4%, 58.6%, and 31.0% in antiviral therapy group and 61.9%, 38.1%, and 14.3% in untreated group, respectively. The overall survival rate of 1-year, 3-year, and 5-year were 86.2%, 68.9%, and 55.2% in antiviral therapy group and 71.4%, 47.6%, and 28.6% in untreated group, respectively. The cumulative disease-free survival rate and overall survival rate of antiviral therapy group were significantly higher than those in the untreated group (P < 0.05). Univariate analysis revealed that the number of tumor, antiviral therapy, and TNM staging were risk factor for tumor-free survival rate, The tumor size, the number of tumor, antiviral therapy, and TNM staging were risk factor for overall survival rate. Multivariate analysis revealed that the number of tumor and TNM staging were independent risk factor for tumor-free survival rate (OR:2.95, 95% CI:1.502-6.114, P < 0.05; OR:4.12, 95% CI:1.972-8.960, P < 0.05), the antiviral therapy and TNM staging were independent risk factor for overall survival rate (OR:3.86, 95% CI:1.745-7.028, P < 0.05; OR:5.17, 95% CI:2.356-11.479, P < 0.05). ConclusionUsing nucleotide analogs antiviral therapy may improve the prognosis after resection of patients with HBV-related HCC.