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.
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.
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.
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.
ObjectiveTo systematically review the efficacy of peginterferon alpha (PEG-IFNα) initially combined with lamivudine (LAM) or adefovir (ADV) in treatment of HBeAg-positive chronic hepatitis B (CHB) patients. MethodsWe electronically searched databases including The Cochrane Library (Issue 11, 2014), PubMed, CBM, CNKI, VIP, and WanFang Data from inception to December 2014, to collect randomized controlled trials (RCTs) about PEG-IFNα initially combined with LAM or ADV for HBeAg-positive CHB. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed by using RevMan 5.2 software. ResultsA total of 11 RCTs involving 2031 patients were included. The results of meta-analysis showed that: After 48 weeks of treatment, the HBsAg seroconversion rate of the PEG-IFNα plus ADV group was significantly higher than that of the PEG-IFNα monotherapy group (8.6% vs. 0%, OR=7.73, 95%CI 1.53 to 39.05, P=0.01) or the ADV monotherapy group (8.5% vs. 0%, OR=7.75, 95%CI 1.07 to 56.23, P=0.04); and the HBsAg seroclearance rate in the combination therapy group was significantly higher than that of the ADV monotherapy group (10.5% vs. 1.2%, OR=5.56, 95%CI to 2.14 to 14.47, P=0.0004). After 52 weeks of treatment, the HBsAg seroconversion rate of the PEG-IFNα plus LAM group was significantly higher than that of the PEG-IFNα monotherapy group (11.6% vs. 5.6%, OR=2.21, 95%CI 1.04 to 4.72, P=0.04). After 26 weeks of follow-up, no significant differences were found between the combination therapy group and the PEG-IFNα monotherapy group in HBsAg seroclearance rate and HBsAg seroconversion rate (all P values >0.05). ConclusionCurrent evidence shows that, compared with PEG-IFNα, LAM, or ADV monotherapy, PEG-IFNα plus LAM or ADV could improve the HBsAg seroclearance or seroconversion rate after 48-52 weeks of treatment for HBeAg-positive CHB, but this effect is still limited. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.
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.
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.
Objective To investigate the clinical efficacy of combined therapy of Gankang Granule and Entecavir for patients with chronic hepatitis B. Methods A total of 118 patients with chronic hepatitis B treated between January 2012 and January 2013 were randomly divided into treatment group (n=59) and control group (n=59). Patients in the treatment group were treated with Gankang Granule and Entecavir, while those in the control group were treated with Entecavir alone. Results Before treatment, there was no significant difference between the two groups in such liver fibrosis evaluation indexes as hyaluronic acid (HA), laminin (LN), procollagenⅢ(PCⅢ), and collegen typeⅣ(CⅣ) (P > 0.05). After treatment, the two groups had significant differences in HA, LN, PCⅢ, and CⅣ(P < 0.05). After 48 weeks of treatment, the alanine aminotransferase recovery rate was significantly different between the two groups (P < 0.05); but there was no significant difference in hepatitis B virus DNA negative conversion rate, hepatitis B e antigen negative conversion rate and hepatitis B e antibody seroconversion rate (P > 0.05). Forty-eight weeks after treatment began, 45 patients underwent liver biopsy which showed that liver fibrosis alleviation was significantly better in the treatment group than the control group (P < 0.05). Conclusions Gankang granule combined with antiviral drug Entecavir for chronic hepatitis B is better in protecting the liver and alleviating hepatic fibrosis than the sole Entecavir. The combined method is worthy of being promoted.
ObjectiveTo evaluate the clinical efficacy and safety of telbivudine (TEV) combined with adefovir dipivoxil (ADV) for chronic hepatitis B (CHB), so as to provide references for clinical practice and research. MethodsWe electronically searched databases including The Cochrane Library (Issue 7, 2013), PubMed, EMbase, Web of Science, CBM, CNKI, VIP, and WanFang Data from inception to August 21st, 2013, for the relevant randomized controlled trials (RCTs). Other sources were also retrieved. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed the quality of included studies. Then, meta-analysis was performed using RevMan 5.1 software. ResultsA Total of 11 RCTs involving 1 010 patients were included. The trial group were given TEV combined with ADV, while the control group were given TEV alone or ADV alone. The results of metaanalysis showed that, the combined use was superior to TEV alone or ADV alone in improving HBV-DNA negative rates at 12-, 24-, 48-weeks, HBeAg negative rates at 12-, 24-, 48-weeks, and ALT recovery rates at 12-, 24-weeks (P < 0.05). The results of qualitative analysis showed that, the trial group had a lower drug resistance rate, and both were alike in the incidence of adverse reaction. ConclusionCompared with TEV alone or ADV alone, TEV combined with ADV could improve the clinical efficacy of treating CHB which is also fairly safe. Due to the limited quantity and quality of the included studies, the aforementioned conclusion still needs to be further verified by conducting more large-scale and high quality RCTs.
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.