白细胞介素28B基因多态性在慢性HBV感染及其治疗中的作用

影响HBV感染/清除及抗病毒疗效的因素极为复杂,如宿主、病毒、环境等。近年来研究证明白细胞介素(IL)28B基因多态性与HCV清除及抗病毒治疗高度相关,国内外许多学者开始关注IL-28B基因变异在慢性乙型肝炎(CHB)中的作用,其中rs12979860、rs12980275、rs8099917 3个位点成为研究热点。总结了IL-28B基因多态性在HBV感染/清除及CHB患者干扰素治疗中的作用,虽然尚无定论,但目前认为IL-28B基因多态性可能在CHB领域中具有重要的潜在临床价值。     

聚乙二醇干扰素α对慢性乙型肝炎患者治疗应答相关因素的研究进展

聚乙二醇干扰素(PEG-IFN)α治疗慢性乙型肝炎(CHB)应答受宿主遗传背景、免疫状态、病毒基因型、病毒载量等多重因素的影响。概述了宿主白细胞介素(IL)28B基因多态性、基线干扰素诱导蛋白10、IL-17A、IL-10、肿瘤坏死因子α水平、病毒载量及基因型、治疗12和24周HBs Ag、HBe Ag血清水平变化为实现HBs Ag、HBe Ag消失及血清学转换、持久病毒学应答的重要预测因素。对近年来关于CHB患者PEG-IFNα治疗应答相关因素研究作一综述。     

促进细胞免疫学应答——慢性乙型肝炎中医药治疗的机制

<正>慢性乙型肝炎(Chronic hepatitis B,CHB)是世界范围的重大传染病,其发生发展受病毒因素(如病毒基因型、病毒变异、病毒复制等)与机体因素(如生物遗传特征、免疫状态、细胞凋亡、细胞坏死等)[1]两方面因素及其相互作用的影响。持续乙型肝炎病毒(Hepatitis B Virus,HBV)复制和宿主抗HBV免疫功能低下是CHB两个重要的临床特征。HBV感染后形成对HBV特异性免疫耐受,导致病毒持续复制不能被清除是HBV感染慢性化、疾病迁延不愈的     

HBV感染免疫学应答的新进展和新观点

乙型病毒性肝炎由HBV感染引起,分为急性HBV感染和慢性HBV感染,慢性乙型肝炎(CHB)为多数亚太地区及中国肝病患者的常见表现。宿主免疫应答与病毒和病毒成分共同作用,导致CHB疾病进展,会经历3个不同时期:免疫耐受期、免疫清除期和免疫活动。全面了解CHB的免疫机制有助于乙型肝炎的抗病毒治疗。本文就HBV感染过程中的免疫分隔化、免疫耐受、Toll样受体及共刺激分子等免疫学机制的一些新进展进行综述。     

慢性乙型肝炎患者HBeAg血清学转换的影响因素

慢性乙型肝炎(CHB)患者血清HBeAg血清学转换在CHB自然史或抗病毒治疗过程中具有重要的意义。本文将重点讨论影响HBeAg血清学转换的因素,如患者ALT水平、病毒基因型、HBV DNA水平、病毒变异和宿主免疫状态等。     

阿德福韦酯治疗HBeAg阳性慢性乙型肝炎患者的生化学应答预测因素分析

阿德福韦酯(ADV)对HBV野生株和拉米夫定耐药变异株均有活性,且耐受性好,不易出现耐药[1].但临床中ADV治疗慢性乙型肝炎(CHB)时,有的疗效较好,有的疗效欠佳,而影响疗效的因素主要包括宿主及病毒.TNF-α是具有广泛生物活性的细胞因子,其单核苷酸多态性反映了不同种族和个体之间的遗传差异[2];而HBV基因型是否影响ADV疗效,相关研究也未得出较一致的结论.为此,本研究同时分析宿主和病毒因素,探讨ADV治疗HBeAg阳性CHB患者48周生化学应答的预测因素,以期提高疗效.     

慢性乙型肝炎的免疫治疗进展

近年来,核苷(酸)类似物和干扰素(IFN)等抗病毒药物已广泛应用于慢性乙型肝炎(CHB)治疗,并取得了一定疗效.现有的抗病毒药物虽可显著抑制HBV复制,并部分恢复宿主的特异性免疫功能,但作用并不持久.慢性HBV感染患者要清除肝内HBV及感染肝细胞,必须依靠有效的特异性抗病毒免疫功能.     

恩替卡韦联合李可肝系培元固本散治疗慢性乙型肝炎的临床观察

正慢性乙型肝炎(CHB)由乙型肝炎病毒(HBV)感染引起,其中15%~40%可以转变为肝硬化及肝癌。抗病毒治疗已被医学界公认为治疗CHB的重要方法。目前,国内外研究认为在HBV持续感染过程中,宿主免疫应答异常是其主要的发病机制,合理调节宿主免疫应答,可以促进HBV持续感染患者对病毒的清除。李可为甘肃省灵石县中医院主任医师,致力于中医临床50余年,崇尚仲景学说,用药擅长融寒温于一炉,以重剂救治重危急诊,     

乙肝病毒基因型对武汉地区慢性乙型肝炎患者干扰素α-2b疗效的影响

目的:探讨武汉地区慢性乙型肝炎(CHB)患者HBV基因型对干扰素α-2b疗效的影响。方法:以患者年龄、性别、基线指标进行匹配,按照基因分型结果分组,比较干扰素治疗48周时的应答情况。结果:在治疗48周结束时,基因B型HBV感染的患者完全应答率和HBeAg阴转率分别为43.8%(28/64)和68.2%(15/22),显著高于C型患者的完全应答率[22.2%(10/45)]和HBeAg阴转率[28.6%(4/14)]。结论:CHB患者HBV的基因型可影响干扰素α-2b的治疗效果,基因B型在治疗48周时应答情况优于基因C型。     

慢性乙型肝炎患者抗病毒治疗过程中的免疫应答特点

宿主的免疫应答是一把双刃剑,参与慢性HBV感染的肝损伤和病毒控制,核苷和核苷酸类药物及干扰素抗病毒治疗可以通过调节宿主免疫应答影响预后。简要论述了宿主免疫应答在慢性HBV感染中的作用及其在抗病毒治疗过程中的特点,指出宿主免疫功能重建在持久HBV感染控制中的重要性。     

To B or not to B

Recent data from mouse models suggest that some phenotypes of X-linked lymphoproliferative disease (XLP) result from impaired T:B-cell interactions.Hislop and colleagues now provide evidence that this may contribute to abnormal responses to Epstein-Barr virus (EBV) in XLP.     

Group B streptococcal polyarthritis complicating hemophilia B

We report a case of polyarticular group B streptococcal infection in an HIV-negative 46-year-old alcoholic with factor IX deficiency. Septic arthritis occurs infrequently in the hemophilic population despite their chronic joint disease; indications for diagnostic arthrocentesis in these individuals are discussed. The group B streptococcus often behaves as an opportunist in adults.     

B protein of factor XIII: differentiation between free B and complexed B

Plasma factor XIII is a complex of A and B proteins noncovalently linked in a tetramer, A2B2, Enzyme-linked immunosorbent assays (ELISA) were developed to measure the separate factor XIII proteins and the complex. All of the A protein in plasma is in the zymogen complex. The B assay measures the total amount of B protein in plasma (both free B and complexed B). This was confirmed by nondenaturing gel electrophoresis and immunoblotting, which showed two bands for B in plasma with this antibody. Two assays were developed to measure A2B2 complex specifically. One assay used a monoclonal antibody to B to bind antigen and measured B protein in the zymogen complex only and hence the concentration of the complex. The specificity of this antibody was also shown by immunoblotting. In the second assay, the capture antibody was to B and the tag antibody was to A. These two assays gave identical results for the concentration of A2B2 (0.07 mumol/L, 21.6 micrograms/mL in normal plasma). Thus, for the first time, differentiation and quantitation of free B and complexed B in plasma was possible. The assays were used to measure factor XIII proteins in plasma from normal controls, homozygous-deficient factor XIII patients, and their heterozygous relatives. The normal concentration of A in plasma is 0.13 to 0.16 mumol/L (approximately 11 micrograms/mL), all of which is in A2B2. The total B concentration is 0.26 to 0.28 mumol/L (approximately 21 micrograms/mL), half of which is complexed. The free B concentration is 0.13 mumol/L (approximately 10 micrograms/mL). Homozygous-deficient patients have essentially no A protein, but their free B concentration is 0.11 mumol/L. Heterozygotes have decreased A2B2, but their free B is 0.11 mumol/L. These results indicate that the concentration of free B is remarkably constant and does not depend on the concentration of A2 or A2B2.     

B safe, B sorted: results of a hepatitis B vaccination outreach programme

The risk of hepatitis B among men having sex with men (MSM) is high, with core antibody rates ranging from 5% to 81%. We describe an outreach, hepatitis B vaccination programme aiming to raise awareness of hepatitis B and increase vaccination uptake. The 13-week programme used an ultra rapid vaccination schedule. Follow-up was defined as complete if the client was core antibody positive, had adequate surface antibody levels following prior vaccination or received three vaccine doses. One hundred and fifty clients were screened for hepatitis B and syphilis. Three cases of untreated syphilis (early latent) and one case of e-antigen-positive hepatitis B were detected. With the aid of text-message reminders, a vaccination completion rate of 76.6% was achieved, with 82.5% completing follow-up. In conclusion, this programme succeeded in reaching MSM not routinely accessing services. Text messaging was an acceptable and effective method of follow-up, resulting in high vaccination completion rates.     

Hepatitis B virus DNA prediction rules for hepatitis B e antigen-negative chronic hepatitis B

After hepatitis B e antigen (HBeAg) seroconversion, hepatitis B may become inactive or progress to HBeAg-negative hepatitis with persistent or intermittent alanine aminotransferase (ALT) elevation. The aim of this study was to prospectively identify factors predictive of the clinical course in HBeAg-negative chronic hepatitis B (CHB). Patients were stratified by ALT and HBeAg status and followed every 3 months for up to 5 years. Kaplan-Meier and Cox regression analysis using the change from normal ALT to elevated ALT as endpoints were performed to determine factors associated with ALT elevation/normalization. Seventy-four HBeAg-negative and 32 HBeAg-positive patients were prospectively evaluated. For HBeAg-negative patients, hepatitis B virus (HBV) DNA was predictive of future ALT. Only 1 patient with normal ALT and an HBV DNA value lower than 10,000 copies/mL developed an elevated ALT within the subsequent year, whereas 67% with an HBV DNA value greater than 100,000 copies/mL had a rise in ALT above normal within 1 year. Patients with a previous history of ALT elevation and longer follow-up at all levels of HBV DNA were more likely to experience ALT elevations. For HBeAg-negative patients with elevated ALT and all HBeAg-positive patients, HBV DNA did not predict future ALT. Other viral and host factors were not predictive of future ALT. CONCLUSION: HBeAg-negative CHB has a fluctuating course. HBV DNA values lower than 10,000 copies/mL predict persistently normal ALT for at least 1 year. Patients with HBV DNA values between 10,000 and 100,000 copies/mL can safely be followed at 6 monthly intervals, whereas HBV DNA values greater than 100,000 copies/mL are highly predictive of future ALT elevation and should prompt regular follow-up.     

Subgenotype reclassification of genotype B hepatitis B virus

ABSTRACT: BACKGROUND: Nine subgenotypes from genotype B have been identified for hepatitis B virus (HBV). However, these subgenotypes were less conclusive as they were often designated based on a few representative strains. In addition, subgenotype B6 was designated twice for viruses of different origin. METHODS: All complete genome sequences of genotype B HBV were phylogenetically analyzed. Sequence divergences between different potential subgenotypes were also assessed. RESULTS: Both phylogenetic and sequence divergence analyses supported the designation of subgenotypes B1, B2, B4, and B6 (from Arctic). However, sequence divergences between previously designated B3, B5, B7, B8, B9 and another B6 (from China) were mostly less than 4%. In addition, subgenotype B3 did not form a monophyly. CONCLUSION: Current evidence failed to classify original B5, B7, B8, B9, and B6 (from China) as subgenotypes. Instead, they could be considered as a quasi-subgenotype B3 of Southeast Asian and Chinese origin. In addition, previously designated B6 (from Arctic) should be renamed as B5 for continuous numbering. This novel classification is well supported by both the phylogeny and sequence divergence of > 4%.     

Prevalence of hepatitis B virus genotype B in Vietnamese patients with chronic hepatitis B

Purpose  Hepatitis B virus (HBV) genotypes can affect treatment response to interferon-based therapy and disease outcomes in patients with chronic hepatitis B (CHB). Little data exist to characterize HBV genotypes in Vietnamese, one of the largest minority groups in the United States and also one with one of the highest CHB and liver cancer disease burdens. The goal of this study was to compare the distribution of HBV genotypes in Vietnamese and Chinese patients. Methods  We performed a cross-sectional study of 567 consecutive patients of Vietnamese (n = 478) or Chinese (n = 89) descent, with HBV genotype mutation analysis performed between 7/2,005 and 6/2,008 at a community gastroenterology clinic and a university-affiliated liver clinic in the United States. Results  There were no significant differences between the Vietnamese and Chinese groups in mean age (45 and 44 years), gender (58% and 61% male), HBeAg status (64% and 65% negative), median alanine aminotransferase (33 and 41 U/L), and log₁₀ HBV DNA (4.9 and 5.0 log₁₀ IU/ml), or the prevalence of precore/basic core promoter mutations (72% and 71%), respectively. Vietnamese patients had a much higher prevalence of HBV genotype B and a lower prevalence of genotype C than Chinese patients: 74% and 25% vs. 55% and 43% (P = 0.001). Conclusions  Chinese patients with CHB often carry either B or C genotype. Vietnamese patients with CHB mostly have HBV genotype B. Additional studies are needed to further characterize the clinical significance of HBV genotype in the natural history and treatment outcomes of CHB in Vietnamese patients.