不同基因型HBV感染患者血清Lp(a)检测及其临床意义分析

目的 探讨乙型肝炎病毒(hepatitis B virus,HBV)感染患者不同基因型与健康人血清脂蛋白(a)[lipoprotein (a),LP(a)]水平相关性的临床意义.方法 分别取HBV感染患者A基因型35例,B基因型57例,C基因型56例,D基因型52例和健康对照64例血清,采用全自动生化分析仪对其脂蛋白(a)进行检测.结果 A,B,C,D四个基因型HBV感染患者的Lp(a)均低于健康对照组(P＜0.05).而且不同基因型HBV感染患者的最终治疗转归率和治愈率不同.结论 HBV能抑制脂蛋白(a)的表达,且其血清中表达水平与乙肝的基因型相关.     

松果菊苷对乙肝病毒复制和抗原表达的影响

以HBV基因转染的HepG2.2.15细胞为体外模型,研究松果菊苷对乙肝病毒(HBV)复制和抗原表达的影响,采用ELISA法测定细胞上清乙肝表面抗原(HBsAg)和E抗原(HBeAg)水平;采用荧光定量PCR法检测HBV DNA水平。以HBV转基因小鼠为体内模型,研究松果菊苷对HBV复制的影响,首先采用荧光定量PCR法检测转基因小鼠肝组织HBV DNA水平,采用ELISA法检测小鼠血清HBsAg和HBeAg水平;同时检测血清转氨酶水平和肝组织病理变化;然后将HBV表达阳性的转基因小鼠随机分为5组:对照组、拉米夫定(50 mg·kg^-1)组和松果菊苷高、中、低剂量(50,25,12.5 mg·kg^-1)组。每天灌胃给药1次,连续给药30 d。第31天分离小鼠血清检测HBV DNA,HBsAg和HBeAg水平;提取肝组织DNA测定其HBV DNA水平,同时作肝组织病理检查。结果表明:松果菊苷在50,100 mg·L^-1作用HepG2.2.15细胞6 d后能显著抑制HBsAg和HBeAg表达,其最高抑制率分别为42.68%,46.29%;同时在100 mg·L^-1对HBV DNA具有抑制作用。此外,松果菊苷在50 mg·kg^-1剂量时能显著抑制HBV转基因小鼠HBsAg与HBeAg表达,其抑制率分别为42.82%,29.12%,同时对转基因小鼠血清HBV DNA水平有显著抑制作用。提示松果菊苷对HBV复制和抗原表达具有较强抑制作用。     

Peg-interferon improves liver histology in patients with HBeAg-positive chronic hepatitis B: no additional benefit of combination with lamivudine.

BACKGROUND: The effect of pegylated interferon or its combination with lamivudine on liver histology of patients with chronic hepatitis B (CHB) is unknown. In a double-blinded, randomized, multi-center study we assessed histological changes in 110 hepatitis B e-antigen (HBeAg)-positive CHB patients treated for 52 weeks with Pegylated interferon alpha-2b (PEG-IFN) in combination with either lamivudine or placebo. Liver biopsies were taken before and at the end of treatment. All biopsies were blinded and scored according to the Ishak system. RESULTS: Necroinflammatory score improved (defined as a decrease of at least two points) in 25 patients (48%) of the PEG-IFN/lamivudine combination therapy group and in 31 patients (53%) of the PEG-IFN monotherapy group. The fibrosis score improved (decrease of at least 1 point) in 17 patients (33%) of the combination therapy group vs. 13 patients (22%) of the PEG-IFN monotherapy group (P=0.23). Responders (n=42), defined as serum HBeAg negative at the end of therapy, showed a larger decline in necroinflammatory score than non-responders (mean decline 2.3 and 1.2 points, respectively, P=0.02). Among patients receiving PEG-IFN monotherapy necroinflammation improved more frequently in responders (78% of responders vs. 43% of non-responders, P=0.01) and in patients who showed normalization of ALT (76% of patients with normal ALT vs. 40% of patients with abnormal ALT, P=0.01). Fibrosis score in the PEG-IFN monotherapy group improved more often in responders (39%) than in non-responders (15%, P=0.04). In the PEG-IFN/lamivudine combination therapy group, we found no significant association between virological and biochemical endpoints and histological improvement. CONCLUSIONS: Treatment with PEG-IFN therapy improves liver necroinflammation in HBeAg-positive CHB patients, particularly in responders to therapy. PEG-IFN also improves fibrosis in responders. Addition of lamivudine to PEG-IFN did not further improve the histological outcome.     

白细胞介素-27的生物学功能及其抗病毒作用的研究进展

白细胞介素-27(IL-27)是IL-6/IL-12细胞因子家族成员之一,由EBI3和p28两个亚基构成异源二聚体,主要来源于树突状细胞(DCs)的分泌.IL-27受体(IL-27R)由WSX-1与gpl30共同组成,多种细胞中均有IL-27R的表达.IL-27对免疫细胞尤其Th1细胞、Th2细胞、Th17细胞、调节性T细胞(Treg)的发育、分化和功能都发挥着不可或缺的作用,它具有免疫促进和免疫抑制双重特点.IL-27的抗病毒作用一直是近年研究的热点,它在抗HIV的研究中较多,对HBV的抗病毒作用也得到了证实.因而IL-27在抗病毒复制中发挥重要作用.     

Possible contribution of prior hepatitis B virus infection to the development of hepatocellular carcinoma

BACKGROUND: The prevalence of prior hepatitis B virus (HBV) infection in hepatocellular carcinoma (HCC) patients and its role in hepatocarcinogenesis are not clear. The aim of the present study is to clarify the importance of prior HBV infection in development of HCC. METHODS: Of 1288 consecutive HCC patients between January 1999 and October 2002, 1008 patients were enrolled. To determine the influence of prior HBV infection in hepatitis B surface antigen (HBsAg)-negative HCC, the prevalence of antibody to hepatitis B core antigen (anti-HBc) was examined according to age, and the clinical features were compared between the anti-HBc positive and the negative groups. RESULTS: The proportion of HBsAg-negative HCC patients, HCC patients with antibody to hepatitis C virus (anti-HCV; C-HCC) and HCC patients negative for both HBsAg and anti-HCV (nBnC-HCC), increased with age. The anti-HBc-positive rates in C-HCC patients also increased with age. Those rates in nBnC-HCC patients were >50% in all age groups. Furthermore, it was found that the anti-HBc-positive rates of these patients were higher than those of corresponding control patients. Tumor size and a positive rate for vessel involvement both in C-HCC and nBnC-HCC patients were larger and higher, respectively, in anti-HBc-positive patients compared with anti-HBc-negative patients, although the difference in nBnC-HCC did not reach statistical significance because of the small numbers. These tumor characteristics were similar to those of B-HCC patients. CONCLUSION: A possible contribution of prior HBV infection to the development of HCC is indicated.     

Novel reporter system to monitor early stages of the hepatitis B virus life cycle

A recombinant hepatitis B virus (HBV) expressing NanoLuc (NL) (HBV/NL) was produced by cotransfecting a plasmid containing a 1.2‐fold HBV genome carrying the NL gene with a plasmid bearing a packaging‐defective 1.2‐fold HBV genome into a human hepatoma cell line, HepG2. We found that NL activity in HBV/NL‐infected primary hepatocytes or sodium taurocholate cotransporting polypeptide‐transduced human hepatocyte‐derived cell lines increased linearly for several days after infection and was concordant with HBV RNA levels in the cells. Treatment of the virus‐infected cells with HBV inhibitors reduced NL activity in a dose‐dependent manner. Detection of HBV/NL infection, monitored by NL activity, was highly sensitive and less expensive than detection using the conventional method to evaluate HBV infection. In addition, because we also studied host factors, this system is applicable not only for studying the HBV life cycle, but also for exploring agent(s) that regulate HBV proliferation.     

合肥市乙型病毒性肝炎感染孕妇KAP调查分析

目的 了解合肥市乙肝感染孕妇母婴阻断知识、信念、行为(KAP)状况,并对其影响因素进行分析,为开展乙肝预防健康教育提供依据。方法 自行设计问卷,在合肥市四个区随机抽取200名乙肝感染孕妇,回收有效问卷169份。采用t检验、logistic回归分析对乙肝感染孕妇KAP得分的影响因素进行分析。结果 乙肝感染孕妇KAP得分总体较低,平均得分为(5.20±2.24)分,及格率为47.31%。分析显示影响乙肝感染孕妇KAP的因素包括学历、居住地、被感染时间等,大专以下学历、居住地在农村的孕妇、母亲不知道自己是否乙型肝炎病毒感染者的孕妇及被感染时间短的孕妇KAP得分较低。结论 公共卫生服务机构应根据乙肝感染孕妇的特征,针对性开展多种形式的健康教育,有效提高乙肝感染孕妇KAP水平。     

Upregulated in Hepatitis B virus-associated hepatocellular carcinoma cells,miR-331-3p promotes proliferation of hepatocellular carcinoma cells by targeting ING5

Hepatitis B virus (HBV) is a major risk factor for development and progression of hepatocellular carcinoma (HCC). It has been reported that viral infection can interfere with cellular microRNA (miRNA) expression and participate in the pathogenesis of oncogenicity. Our miRNAs array data indicated that miR-331-3p expression in HCC cell lines increased, but the relationship between miR-331-3p expression and HBV activity is unclear. Here, we observed elevated expression of miR-331-3p in different HCC cell lines expressing HBV. HBV, especially HBx, promotes miR-331-3p expression by enhancing its promoter activity. Using a miRNA target prediction database miRBase, we identified ING5 to be a novel target gene of miR-331-3p. miR-331-3p could inhibit ING5 expression by directly targeting its 3′-untranslated region (3′-UTR). As predicted, HBV was confirmed to repress ING5 at both mRNA and protein levels by promoting miR-331-3p expression. Our result indicated that miR-331-3p expression promotes proliferation of SMMC7721 cells by inhibiting ING5. ING5 overexpression promoted cell apoptosis in HCC cell lines. We also found ING5 expression was decreased in tumor tissue of HCC patient with HBV infection compared to its expression in para-carcinoma tissues. Conclusion: These results showed that miR-331-3p is upregulated by HBV and promotes proliferation of HCC cells though repression of ING5 expression. These data provide new insights for understanding the mechanisms of HBV-related HCC pathogenesis.