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.
目的 比較拉米夫定+阿德福韋酯聯合治療與阿德福韋酯單藥治療對阿德福韋酯停藥后出現病毒學反彈而無基因型耐藥變異患者的療效及安全性。 方法 回顧研究2007年1月－2012年1月在傳染科門診就診的67例阿德福韋酯治療獲得病毒學應答但停藥后出現病毒學反彈的e抗原陽性慢性乙型肝炎患者，分別給予拉米夫定+阿德福韋酯聯合治療（聯合組，n=35）和阿德福韋酯單藥治療（單藥組，n=32）。 結果 治療1年后，聯合組（32例，85.7%）較單藥組（21例，65.6%）有更多的患者重新獲得了丙氨酸轉氨酶復常（P=0.009），聯合組34例（97.1%）乙型肝炎病毒DNA陰轉，單藥組22例（68.8%）陰轉，兩組差異有統計學意義（P=0.002）；在血清學轉換方面，聯合組和單藥組分別有4例（11.4%）和1例（3.1%）患者獲得了e抗原的血清學轉換。在治療中所有患者均未發生任何嚴重不良反應。 結論 阿德福韋酯停藥后出現病毒學反彈，選擇拉米夫定與阿德福韋酯聯合治療可使患者重新獲得較好的生化學和病毒學應答。
ObjectiveAntiviral treatments could benefit chronic hepatitis B (CHB) patients with the regression or improvement of liver fibrosis. However, the degree of dynamic change of liver fibrosis for patients who had not received antiviral treatment remained to be studied. The current study aimed to observe the long-term variation of liver stiffness measurement (LSM), virological and biochemical response on patients without standard antiviral therapy.MethodsA total of 220 patients who were diagnosed with chronic HBV infection, who had not reached the standard of antiviral therapy, and completed a follow-up date of over 2 years in the First Affiliated Hospital of Xi’an Jiaotong University from 2012 to 2018 were retrospectively enrolled. According to the changes of LSM in baseline and follow-up period, the patients were divided into regression group, non-progressive group, and progressive group. The virological and biochemical characteristics of each group were analyzed.ResultsAmong the 220 patients, 153 patients (69.5%) had no progress in LSM degree. Alanine aminotransferase (ALT), HBV DNA, and HBsAg in a few patients increased or slightly decreased, while the vast majority remained in a relatively stable state. 89.5% (137/153) of the non-progressive patients were in grade F0. In addition, 58 patients showed spontaneous improvement with a decreasing rate of 0.460 kPa per year. Patients with ALT of 1-2 ULN had a statistically significant decrease in LSM improvement compared to patients with normal ALT. 82.8% of the LSM-improving patients showed baseline LSM of F1-F3. Only 9 patients showed LSM deterioration, however, which could not be explained by virus replication or necroinflammatory activity. ConclusionsFor patients unsatisfying standard antiviral therapy, most patients with baseline LSM of F0 grade fail to progress, and patients with baseline LSM of F1-F3 show a decrease during follow-up, LSM progression occurs in 4.1% of patients.
ObjectiveTo systematically review the efficacy and safety of Heluo Shugan capsule in the treatment of hepatitis B fibrosis. MethodWe searched PubMed, The Cochrane Library (Issue 8, 2015), CBM, CNKI, VIP and WanFang Data from their inception to August 2015, to collect randomized controlled trials (RCTs) on Heluo Shugan capsule for hepatitis B fibrosis. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then meta-analysis was performed using RevMan 5.3 software. ResultsA total of 15 RCTs involving 1 840 patients were included. The results of meta-analysis showed that: (1) As for reduced level of serum hyaluronic acid (HA), Heluo Shugan capsule was superior to placebo (MD=82.31, 95%CI 37.44 to 127.19, P=0.000 3), but worse than Fuzheng Huayu capsule (MD=-137.45, 95% CI-196.29 to-78.62, P < 0.000 01), Fufang Biejia Ruangan tablet (MD=-51.19, 95% CI-67.58 to-34.81, P < 0.000 01) and Anti-fibrosis decoction (MD=-82.13, 95% CI-102.37 to-61.88, P < 0.000 01). (2) As for reduced level of serum laminin (LN), Heluo Shugan capsule was superior to placebo (MD=36.83, 95% CI 11.84 to 61.82, P=0.004), but worse than Fufang Biejia Ruangan tablet (MD=-36.00, 95% CI-64.29 to-7.71, P=0.01), Ganfujian capsule (MD=-22.14, 95% CI-37.28 to-7.00, P=0.004) and Anti-fibrosis decoction (MD=-38.64, 95% CI-75.00 to-2.29, P=0.04). (3) As for reduced level of serum procollagen type III peptide (PCIII), Heluo Shugan capsule was superior to placebo (MD=47.17, 95% CI 32.68 to 61.66, P < 0.000 01), but worse than Fuzheng Huayu capsule (MD=-4.80, 95% CI-9.08 to-0.51, P=0.03), Dahuang Zhechong pills (MD=-53.77, 95% CI-105.01 to-2.53, P=0.04), Ganfujian capsule (MD=-46.82, 95% CI-66.30 to-27.34, P < 0.000 01) and Anti-fibrosis decoction (MD=-28.68, 95% CI-55.59 to-1.77, P=0.04). (4) As for reduced level of serum type-IV-collagen (IV-C), Heluo Shugan capsule was superior to placebo (MD=72.77, 95% CI 47.65 to 97.89, P < 0.000 01), but worse than Fuzheng Huayu capsule (MD=-34.69, 95% CI-56.65 to-12.73, P=0.002), Dahuang Zhechong pills (MD=-21.26, 95%CI-38.79 to-3.73, P=0.02), Fufang Biejia Ruangan tablet (MD=-69.04, 95%CI-124.38 to-13.69, P=0.01), Ganfujian capsule (MD=-19.84, 95% CI-37.41 to-2.27, P=0.03) and Anti-fibrosis decoction (MD=-37.98, 95% CI-72.99 to-2.96, P=0.03). ConclusionCurrent evidence shows that, Heluo Shugan capsule was superior to placebo, but worse than Fufang Biejia Ruangan tablet, Fuzheng Huayu capsule, Dahuang Zhechong pills, Ganfujian capsule and Anti-fibrosis decoction in reducing the level of serum hepatic fibrosis. Due to the limited quantity and quality of included studies, more high-quality, large-scale RCTs are need to verify the above conclusion.
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 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.
ObjectiveTo systematically evaluate the association between human leukocyte antigen DQ (HLA-DQ) gene rs2856718A>G, rs9275572A>G polymorphisms and the risk of chronic hepatitis B. MethodsPubMed, EMbase, CBM, WanFang Data, CNKI and VIP databases were systematically searched from inception to April 2015 to collect case-control studies about HLA-DQ gene polymorphisms and the risk of chronic hepatitis B. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.3 software, and Stata 12.0 software was used for sensitivity and publication bias analysis. ResultsA total of 6 papers involving 8 case-control studies were included, which involved 3 690 cases and 6 267 controls. The results of meta-analysis showed that:the rs2856718A>G polymorphism was associated with the decreased risk of chronic hepatitis B (AG+GG vs. AA:OR=0.63, 95%CI 0.51 to 0.78, P=0.000; GG vs. AG+AA:OR=0.69, 95%CI 0.61 to 0.79, P=0.000; GG vs. AA:OR=0.56, 95%CI 0.48 to 0.64, P=0.000; GA vs. AA:OR=0.64, 95%CI 0.47 to 0.88, P=0.006; G vs. A:OR=0.74, 95%CI 0.68 to 0.79, P=0.000). The rs9275572A>G polymorphism was not associated with the risk of chronic hepatitis B (AG+GG vs. AA:OR=1.11, 95%CI 0.55 to 2.23, P=0.770; GG vs. AG+AA:OR=1.10, 95%CI 0.84 to 1.45, P=0.500; GG vs. AA:OR=1.14, 95%CI 0.54 to 2.41, P=0.730; AG vs. AA:OR=1.06, 95%CI 0.56 to 2.02, P=0.860; G vs. A:OR=1.11, 95%CI 0.83 to 1.48, P=0.490). ConclusionHLA-DQ gene rs2856718 A>G polymorphism is significantly associated with decreased risk of chronic hepatitis B, but the rs9271319 A>G polymorphism is not associated with the risk of chronic hepatitis B.
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.