【摘要】 目的 分析慢性乙肝患者血清生化、血常规、血清病毒载量及乙型肝炎标志物与肝组织炎症分级、纤维化分期的相关性,以找到有较好相关性的临床指标；通过肝活检证实临床诊断与病理诊断的符合情况,探讨肝活检的重要性及价值。方法 对2007年6月—2009年8月在传染科行肝穿刺活检的359例慢性乙型肝炎患者的血清丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)、总胆红素(TB)、白蛋白(ALB)、球蛋白(GLB)等指标,白细胞(WBC)、血小板(PLT)等指标,凝血酶原时间(PT),血清HBV DNA定量及乙肝标志物的不同状态与肝穿病理分级、分期的相关性进行分析；统计慢性乙肝患者临床诊断与病理诊断的符合情况。结果 肝组织炎症分级及纤维化分期之间有一定相关性(Plt;0.05)；血清ALT、AST、ALB、GLB、PT有助于判断肝组织炎症程度(Plt;0.05)；ALB、GLB、WBC、PLT、PT对肝组织纤维化程度的评估有意义(Plt;0.05)；HBV DNA复制水平与肝组织炎症及纤维化无关(Pgt;0.05),但存在负相关的趋势；纤维化程度高的患者HBeAg阴性组较HBeAg阳性组更多(Plt;0.05)。慢性乙型肝炎患者临床与病理诊断总符合率为56.3％。结论 动态监测慢性乙肝患者肝功能、血常规、凝血常规在一定程度上有助于判断疾病的程度,但要确诊肝组织炎症分级及纤维化分期,肝组织病理活检是必需的。
ObjectivesTo systematically review the risk factors of hepatocellular carcinoma (HCC) in patients with hepatic B surface antigen (HBsAg).MethodsScopus, EMbase, PubMed, and The Cochrane Library databases were systematically searched for relevant studies on HCC after HBsAg seroclearance from inception to October 31st, 2017. Two reviewers independently screened literature, extracted the data, and evaluated the risk of bias in the included studies. Meta-analysis was then conducted using R 3.5.3 software.ResultsA total of 28 studies involving 105 411 patients were included. Among 105 411 patients with chronic hepatitis B (CHB), 7 656 patients occurred spontaneously HBsAg seroclearance, while 1 248 patients had HBsAg seroclearance after interferon or nucleoside analogue therapy. The rate of HBsAg seroclearance was 6.77%. Meta-analysis showed that risk factors for HCC after serum HBsAg conversion included cirrhosis (OR=6.43, 95%CI 3.56 to 11.60, P<0.001), male (OR=2.72, 95%CI 1.66 to 4.46,P<0.001), and age ≥50 years at HBsAg seroclearance (OR=3.71, 95%CI 2.17 to 6.35,P<0.001).ConclusionsPatients with CHB after HBsAg seroclearance are still at risk of developing HCC. Therefore, periodic surveillance is recommended, especially for male patients, patients with cirrhosis, and patients who experience HBsAg seroclearance when over 50.
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 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 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.
Objective To evaluate the effectiveness and safety of foscarnet sodium in the treatment of chronic hepatitis B. Methods We searched MEDLINE, EMbase, The Cochrane Library and CNKI from 1978 to June 2006. Randomized controlled trials of foscarnet sodium versus other drugs or no drugs in the treatment of chronic hepatitis B were identified. The quality of the included trials was evaluated by two reviewers independently. Meta-analysis was done using The Cochrane Collaboration’s RevMan 4.2.7. Results Seven studies (337 patients) were included; one compared foscarnet sodium versus interferon, and the other six compared foscarnet sodium versus no drugs. All the included studies were graded in terms of the quality of randomization, allocation concealment and blinding. All 7 studies were graded as level C. The meta-analysis showed that: ① foscarnet sodium was not significantly different from interferon in clinical efficacy, liver function, negative-conversion rate of virological markers and side effects. ② compared with the no drugs group, the negative-conversion rate of virological markers was significantly higher for the foscarnet sodium group, HBeAg (RR 6.20, 95%CI 1.76 to 21.79) and HBV-DNA (RR 4.13, 95%CI 1.32 to 12.86); but there were no significant differences in clinical efficacy, liver function and side effects. Conclusions Available evidence shows that: in the treatment of chronic hepatitis B the effectiveness and safety of foscarnet sodium are not significantly different from interferon, but only one trial is included in this review, so the evidence is weak. Compared with no drugs, foscarnet sodium significantly improves the negative-conversion rate of virological markers, but the evidence is insufficient to show whether foscarnet sodium could improve clinical efficacy and liver function, as well as reduce side effects.
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.
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 investigate the needs for health education in chronic hepatitis B patients, in order to provide a theoretical basis for taking pertinent nursing intervention. MethodsBetween July and December 2011, self-made questionnaires on the needs for health education were used to investigate 70 in-patients with chronic hepatitis B. Meanwhile, factors associated with the needs of health education such as age, education, and the course of the disease were also analyzed. ResultsThe differences in the needs of health education were statistically significant among patients with different cultures, ages, and courses of disease (P<0.01). The needs of health education were correlated with culture, age and courses of disease. ConclusionThere are some deficiencies in the health education for chronic hepatitis B patients. In clinical practice, health education should be multidimensional and continuous based on the age, education degree and the course of the disease.
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.