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 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 Hepatitis B virus X (HBx) protein is involved in the initiation and progression of hepatocellular carcinoma (HCC) by regulating the host protein-coding genes. Herein, we want to explore whether HBx protein can alter the expression of microRNAs (miRNAs) to promote proliferation and transformation in malignant hepatocytesin vitro. Methods MiRNA microarray and quantitative reverse-transcription polymerase chain reactions (qRT-PCRs) were performed to identify miRNAs that were differentially regulated by HBx protein in HCC cells. Protein and mRNA expression analyses, cell cycle and apoptosis analyses, and luciferase reporter assays were performed to delineate the consequences of miR-16 family repression in HepG2 cells. Results HBx protein induced widespread deregulation of miRNAs in HepG2 cells, and the downregulation of the miR-16 family was reproducible in HepG2, SK-HEP-1, and Huh7 cells. CCND1, a target gene of the miR-16 family, was derepressed by HBx protein in HepG2 cells. C-myc mediated the HBx-induced repression of miR-15a/16 in HepG2 cells. Ectopically expressed miR-15a/16 suppressed the proliferation, clonogenicity, and anchorage-independent growth of HBx-expressing HepG2 cells by arresting them in the G1 phase and inducing apoptosis, whereas reduced expression of miR-16 accelerated the growth and cell-cycle progression of HepG2 cells. Conclusions HBx protein altered thein vitro expression of miRNAs in host malignant hepatocytes, particularly downregulating the miR-16 family. Repression of miR-15a/16 is c-myc mediated and is required for the HBx-induced transformation of HepG2 cellsin vitro. Therefore, miR-16 family may serve as a therapeutic target for hepatitis B virus (HBV)-associated HCC.
At present, the most commonly used nucleoside (acid) anaog (NAs) treatment regimen in clinical practice cannot completely cure chronic viral hepatitis B (CHB). However, although the polyethylene glycol interferon treatment regimen is superior to the NAs regimen in terms of immune mechanism, it has the disadvantage of low hepatitis B virus DNA response rate. In recent years, the cure of CHB is being studied all over the world. Various mechanisms and drug targets are being explored, and diversified therapeutic strategies are also being used. Clinical cure of hepatitis B is possible, but it is still in the early stage, and many potential drugs and better therapeutic strategies are still being tested. This article mainly reviews the latest progress in the treatment of CHB based on the recent research achievements in direct antiviral drugs and host immunotherapy as well as the research progress in combination therapy.
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.