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.
目的 觀察阿德福韋酯聯合胸腺五肽治療乙型肝炎病毒e抗原（HBeAg）陽性慢性乙型肝炎2年的療效。 方法 2007年1月－2009年1月間178例慢性乙型肝炎患者隨機分為試驗組91例和對照組87例。試驗組給予胸腺五肽1 mg，隔日皮下注射，療程52周；同時阿德福韋酯10 mg/d口服104周。對照組給予阿德福韋酯10 mg/d，口服104周。治療26、52、104周及停藥52周時，分別檢測血清丙氨酸氨基轉移酶（ALT）、天冬氨酸氨基轉移酶（AST）、乙型肝炎病毒（HBV）DNA含量及HBV血清標志物。 結果 治療52周后，試驗組在ALT復常率、AST復常率、HBV DNA轉陰率、HBeAg轉陰率與HBeAg/HBeAb血清轉換率方面都比對照組高。停藥52周時，試驗組與對照組的ALT復常率、AST復常率、HBV DNA轉陰率、HBeAg轉陰率、HBeAg/HBeAb血清轉換率分別為74.73%與51.72%、75.82%與54.02%、25.27%與8.05%、26.37%與10.34%、18.68%與8.05%（χ2=10.652、9.313、9.421、7.574、4.313，P＜0.05）。 結論 阿德福韋酯聯合胸腺五肽治療HBeAg陽性慢性乙型肝炎比單獨使用阿德福韋酯抗病毒治療效果更好，有助于提高HBeAg/HBeAb血清轉換率，減少停藥后病毒學突破，并且使用安全。Objective To evaluate the efficacy of adefovir dipivoxil (ADV) combined with thymopentin on chronic hepatitis B patients with positive hepatitis B e antigen (HBeAg). Methods Between January 2007 and January 2009, 178 chronic hepatitis B patients with positive HBeAg were randomly divided into two groups: the treatment group (91 cases) and the control group (87 cases). All patients in two groups received 10 mg of ADV once a day for 104 weeks, while the patients in the treatment group received 1 mg of thymopentin for subcutaneous injection every other day for 52 weeks. The rates of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) normalization, serum hepatitis B virus (HBV) DNA clearance and HBeAg loss and anti- HBeAg seroconversion were evaluated at pretreatment, and 52, 104 and 156 weeks after treatment, respectively. Results After 52-week treatment, The rates of ALT and AST normalization, serum HBV DNA clearance and HBeAg loss and anti- HBeAg seroconversion in the treatment group were higher than those in the control group. In 52-week follow-up after 104 weeks treatment, the rates of ALT and AST normalization , serum HBV DNA clearance and HBeAg loss and anti- HBeAg seroconversion of two groups were 74.73% versus 51.72%, 75.82% versus 54.02%, 25.27% versus 8.05%, 26.37% versus 10.34%, 18.68% versus 8.05%, respectively (χ2 = 10.652, 9.313, 9.421, 7.574, 4.313; P＜0.05). Conclusions It is more effective for adefovir dipivoxil combined with thymopentin on HBeAg-positive patients with chronic hepatitis B than using adefovir alone. Combination treatment could improve the rates of HBeAg seroconversion and reduce the breakthrough of HBV after drug withdrawal. And it is safe.
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.
Objective To review the efficacy and safety of Kushenin combined with Adefovir Dipivoxil for Chronic Hepatitis B (CHB). Method Randomized controlled trails of Kushenin combined with Adefovir Dipivoxil for CHB were gathered from PubMed, CBMdisc (1978 to 2009), and CSJD (1989 to 2009), while other relative researches were searched manually; every research was evaluated, and then analyzed with RevMan 5.0.0 software. Result Ten randomized controlled trials were included; among total 855 patients, 436 were in trial group and the other 419 were in control group. As the Meta-analysis showed, the therapeutic effect of kushenin combined with Adefovir Dipivoxil was better than that of Adefovir Dipivoxil in aspects of improving the negative rate of serum ALT (RR=1.28, 95%CI 1.17 to 1.40), the negative rate of serum HBV-DNA (RR=1.27, 95%CI 1.13 to 1.42), the negative rate of serum HBeAg (RR=1.80, 95%CI 1.32 to 2.44), and the conversion rate of HBeAg and anti-HBe (RR2.06, 95%CI 1.43 to 2.95). Conclusion Kushenin combined with Adefovir Dipivoxil in treating CHB can improve the conversion rate of HBeAg and anti-HBe and further take better therapeutic effect.
Background Hepatitis B virus infection is a serious health problem worldwide. Traditional Chinese medicinal herbs have been widely used to treat chronic liver diseases, and many controlled trials have been done to investigate their efficacy. Objectives To assess the efficacy and safety of traditional Chinese medicinal herbs for chronic hepatitis B infection. Search strategy Searches were applied to the following electronic databases: the CHBG Trials Register, the Cochrane Complementary Medicine Field Trials-Register, the Cochrane Library, MEDLINE, EMBASE and BIOSIS. Five Chinese journals and conference proceedings were handsearched. No language restriction was used. Selection criteria Randomized or quasi-randomized trials with at least three months follow-up. Thais of Chinese medicinal herbs (single or compound) compared with placebo, no intervention, general non-specific treatment or interferon treatment were included. Trials of Chinese medicinal herbs plus interferon versus interferon alone were also included. Trials could be double-blind, single-blind or not blinded. Data collection and analysis Data were extracted independently by two reviewers. The methodological quality of trials was evaluated using the Jadad-scale plus allocation concealment. Intention-to-treat analyses were performed. Main Resuits Nine randomized trials, including 936 patients, met the inclusion criteria. Methodological quality was considered adequate in only one trial. There was a significant funnel plot asymmetry (regression coefficient= 3.37, standard error 1.40, P=0.047). Ten different medicinal herbs were tested in the nine trials. Compared to non-specific treatment or placebo, Fuzheng Jiedu Tang (compound of herbs) showed significantly positive effects on clearance of serum HBsAg, HBeAg, and HBV DNA; Polyporus umbellatus, polysaccharide on serum HBeAg and HBV DNA; Phyllanthus amarus on serum HBeAg. Phyllanthus compound and kurorinone showed no significant effect on clearance of serum HBeAg and HBV DNA and on alanine aminotransferase normalization compared to interferon treatment. There were no significant effects of the other examined herbs. Reviewer’s conclusions Some Chinese medicinal herbs may work in chronic hepatitis B. However, the evidence too weak to recommend any single herb. Rigorously designed, randomized, double-blind, placebo-controlled trials are required.
Objective To compare lamivudine monotherapy versus lamivudine-thymosin alpha-1 combination therapy for HBeAg positive chronic hepatitis B. Methods We searched CENTRAL (Issue 4, 2008), PubMed (up to December 2008), the Chinese Biomedical database (CBM, up to December 2008), and CNKI (up to December 2008). We also scanned references of all included studies and pertinent reviews. Quality assessment and data extraction were conducted by two reviewers independently. Meta-analyses were conducted using RevMan 5.0. Results We identified 23 trials involving 1 488 patients. According to the results of meta-analyses, the HBeAg seroconversion rate of the combination therapy group was higher than that of the monotherapy group, both at the end of the treatment and the one year follow-up (RR=2.89, 95%CI 2.40 to 3.48; RR=4.99, 95%CI 2.99 to 8.31); and there were also significant differences between the two groups for secondary outcomes including HBV-DNA negative, ALT normalization, etc.. There was no significant difference between the two groups in adverse reaction. Conclusion Lamivudine-thymosin alpha-1 combination therapy might be more effective than lamivudine monotherapy for HBeAg positive chronic hepatitis B. However, the results should be interpreted with caution because of the low quality of the included studies. High-quality, large scale randomized controlled trials are needed to further prove the results.
【摘要】 目的 分析腺苷蛋氨酸治療慢性乙型肝炎高膽紅素血癥的臨床療效。 方法 回顧性分析2010年1-12月28例接受腺苷蛋氨酸（2 000 mg靜脈滴注，1次/d）治療慢性乙型肝炎高膽紅素血癥患者的臨床資料，并對腺苷蛋氨酸治療慢性重癥乙型肝炎高膽紅素血癥后癥狀、體征及實驗室檢測指標的改變情況進行總結，利用多因素logistic回歸分析方法探索與療效相關的預測因素。根據相關癥狀、體征和實驗室結果的不同，將療效分為顯效、有效和無效3類。 結果 28例患者使用腺苷蛋氨酸治療4周后，顯效20例（71.4%），有效4例（14.3%），無效4例（14.3%）。多因素logistic回歸分析提示病程短、并發癥少是影響腺苷蛋氨酸療效的獨立預測因素。 結論 腺苷蛋氨酸是治療慢性乙型肝炎高膽紅素血癥有效，發病時間短及并發癥少的患者退黃效果更好。【Abstract】 Objective To investigate the curative efficacy of ademetionine in the treatment of hyperbilirubinemia for chronic hepatitis B patients. Methods The clinical data of 28 chronic hepatitis B patients with intrahepatic cholestasis receiving intravenous ademetionine treatment (2 000 mg per day) were retrospectively analyzed. Patients’ symptoms, body signs and laboratory examination results were summarized, and predictors for efficacy were investigated using multiple regression analysis. In this study, the curative efficacy was classified into remarkable efficacy, efficacy and inefficacy, according to the clinical data. Results After one-month treatment with ademetionine, the percentage for remarkable efficacy, efficacy and inefficacy was 71.4%, 14.3%, and 14.3% respectively. Multivariate logistic regression analysis showed that short disease duration and fewer complications were independent predictors for remarkable efficacy of ademetionine treatment. Conclusion Ademetionine is an effective agent for the treatment of hyperbilirubinemia in chronic hepatitis B patients, and the result is especially good for patients with short duration and fewer complications.
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.
Objective To evaluate the efficacy of adefovir monotherapy (ADF) versus adefovir-Matrine combination therapy (ADF+M) for chronic hepatitis B. Methods Such databases as The Cochrane Library, MEDLINE, PubMed, CBM, CNKI, WanFang and VIP Database were searched from the date of their establishment to July 2010, and the references of all included studies were also traced so as to identify randomized controlled trials (RCTs) of ADF versus ADF+M. Quality assessment and data extraction were conducted in accordance with the Cochrane Handbook 5.0.2 by two reviewers independently. Meta-analyses were conducted by using RevMan 5.0 software. Results A total of 24 RCTs involving 2 092 patients were included. The results of meta-analyses showed that at the end of the treatment for both six months and 12 months, respectively, the ADF+M group was superior to ADF group with a significant difference in both the HBeAg seroconversion rate as the primary outcome (six months: RR=2.05, 95%CI 1.53 to 2.74; 12 months: RR=2.13 95%CI 1.74 to 2.60) and the secondary outcome such as HBV-DNA negative conversion, HBeAg negative conversion, ALT normalization, HBV-DNA variation, complete response and HBsAg negative conversion, etc. Conclusion As the current evidence shows, ADF+M therapy is superior to ADF therapy for chronic hepatitis B. The significant difference can even be observed at the end of the treatment for six months. 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.