慢性乙型肝炎的抗病毒治疗

慢性乙型病毒性肝炎(CHB)一直是一个全球性健康问题，全球大约3．5亿人感染乙肝病毒(HBV)。在慢性HBV感染的病程中，约15％～40％将产生并发症，如重症肝炎、肝硬化、肝功能衰竭及肝细胞肝癌(HCC)。目前，CHB的治疗目的仅在于抑制乙型肝炎病毒(HBV)的复制，缓解肝脏病变，本综述总结α-干扰素和拉米夫定在治疗慢性乙肝有效性和安全性的资料，不同临床状态下的治疗策略和未来的治病方向。     

乙型肝炎病毒感染的抗病毒治疗

乙型肝炎病毒 (ＨＢＶ)感染的抗病毒治疗在 2 0世纪的最后 10年内取得了重大突破 ,α 干扰素 (ＩＦＮ α)及核苷类似物的临床应用 ,改善了ＨＢＶ相关肝脏疾病的自然病史和预后 ,近年来已在抗病毒治疗领域积累了初步的经验 ,并对今后的研究方向有了新的认识。1　抗病毒治疗的研究现状1.1　ＩＦＮ α　人们对抗病毒治疗的研究始于ＩＦＮ α的单药应用。超过 10年的治疗研究证实 ,ＩＦＮ α是慢性乙肝治疗的有效药物 ,其抗病毒的机制包括激活体内特异和非特异杀伤细胞 ,促进病毒抗原和Ｉ型主要组织相容性 (抗原 )复合物的表达 ,增强机体的免疫…     

慢性乙型肝炎抗病毒治疗的现状及进展

目前慢性乙型病毒性肝炎(chronic hepatitis B,CHB)的治疗包括聚乙二醇化干扰素(pegylated interferon,PEG-IFN)和核苷(酸)类似物[nucleos(t)ide analogs,NAs]。基于IFN的治疗时间是有限的,但只有20%~30%的患者实现血清学反应和持续的治疗后反应。NAs因其长期疗效有限导致治疗期延长,并且长期服用NAs可出现耐药突变体。很多研究结合PEG-IFN的免疫调节特性以及NAs的直接抗病毒活性,试图提高CHB患者的疗效。联合治疗虽然提高了患者的治疗中应答率,但并未改善治疗后反应。因此,目前迫切需要探索新的治疗策略。     

慢性乙型肝炎抗病毒治疗方法探讨

目的：寻找治疗慢性乙型肝炎的有效方法,做到因病而治,因人而治的优化治疗,改善患者预后,提高患者生活质量。方法选择2001年至2009年朔州市人民医院收治的慢性乙型肝炎和乙肝肝硬化患者568例,将这些患者随机分为5个不同的治疗组,分别选择不同抗病毒治疗方案,观察5组抗乙型肝炎病毒疗效。结果不同的抗病毒治疗方案有不同的效果,随着抗病毒治疗时间的延长,各项观察指标均有所好转。结论临床医师应根据患者的个体差异选择不同的抗病毒治疗方案,延长抗病毒治疗时间,以更好地抑制乙型肝炎病毒复制,达到改善患者预后、提高生活质量的目的。     

未经抗病毒治疗的乙型肝炎病人的乙肝病毒YMDD变异分析

目的探讨未经抗病毒治疗的慢性乙型肝炎患者中HBV多聚酶YMDD变异情况及与乙肝血清标志物等之间的相关性。方法在进行HBV-DNA定量检测基础上,根据HBV-DNA含量不同随机选取89例未经抗病毒治疗的慢性乙型肝炎患者,同时进行YMDD变异及乙肝三系检测。结果89例未经抗病毒治疗的慢性乙型肝炎患者YMDD变异率达13.5%,YM-DD变异株以YIDD为主,占12.4%,YVDD占1.1%,并且其变异主要发生在HBeAg阳性患者中,HBeAg阳性变异株占10.1%,HBeAb阳性占3.4%。结论未经抗病毒治疗的乙肝患者中仍存在较高的YMDD变异率,变异者中以YIDD变异株为主,且主要发生在HBeAg阳性患者当中。     

慢性乙型肝炎抗病毒治疗

我国乙型肝炎病毒（hepatitis B virus,HBV）感染者众多,严重危害广大人民的健康和生命安全,也给国家及家庭造成巨大经济负担。随着抗乙肝病毒药物的不断出现和在临床的广泛应用,如何科学合理地应用抗病毒药物,     

乙型肝炎肝硬化的抗病毒治疗

据世界卫生组织（WHO）报道，全球60亿人口中约1／2的人生活在乙型肝炎病毒（HBV）高流行区。全球约有20亿人感染了HBV，其中6．9亿人在中国；全球有乙型肝炎病毒表面抗原（HBsAg）携带者3．5亿人，其中1／3在中国；全世界每年有75万人死于HBV感染引起的疾病，其中28万人来自中国，其中25％～40％最终将死于肝硬化和肝癌。在全球前十位疾病死因中，慢性乙型肝炎（简称乙肝）占第7位，每年因慢性乙肝死亡者约为75万例。乙肝肝硬化患者发生肝细胞肝癌的五年累计危险度在亚洲为17％，在欧洲和北美为10％，五年肝病相关性死亡率在亚洲为14％，欧洲为15％。     

近郊孕妇乙型肝炎病毒感染情况分析

目的了解怀孕妇女乙型肝炎(下称乙肝)病毒感染情况。方法采用酶联免疫吸附试验检测乙肝病毒(HBV)标志物。结果 225例怀孕妇女HBV感染者14例,乙肝病毒表面抗原(HBsAg)阳性、乙肝病毒e抗原(HBeAg)阳性、乙肝病毒核心抗体(抗-HBc)阳性9例,乙肝病毒e抗体(HBsAg)阳性、抗-HBe阳性、抗-HBc阳性5例,有免疫力者80例。结论围生期检查HBV标志物是降低新生儿感染率的当务之急。     

乙型肝炎病毒母婴阻断的抗病毒治疗研究进展

母婴传播是我国乙型肝炎病毒主要传播途径之一,虽经积极的主、被动联合免疫治疗,但仍有部分婴儿感染乙型肝炎病毒。目前孕妇抗病毒治疗结合新生儿主、被动联合免疫是阻断乙型肝炎病毒母婴传播的有效方法,但抗病毒治疗的有效性及安全性越来越受到关注,本文对抗病毒治疗的耐药性、肝功能异常情况、停药时机选择等研究进展作一综述。     

Genetic variability of hepatitis B virus and response to antiviral therapy

Hepatitis B virus (HBV) infection is a global health issue. Effective and individualized treatment of chronic hepatitis B to prevent progression to end-stage liver diseases and hepatocellular carcinoma is needed. HBV can be classified into eight genotypes (A-H) on the basis of genome sequence divergence. In addition, several naturally occurring HBV mutants have also been identified. The epidemiology of HBV genotypes and their implications for response to antiviral therapy have become increasingly recognized. Recent studies suggested that responses to standard interferon treatment in patients with genotype A or B are better than those with genotype C or D; however, conflicting results exist regarding the response to pegylated interferon. The influence of dose and duration on interferon-based therapy remains to be clarified. In addition to genotype, naturally occurring mutations such as precore and core promoter mutations have also attracted much attention, because they have been shown to affect the disease progression of HBV-related chronic liver disease and possibly the response to antiviral therapy. Here, we review the differences in antiviral theraputic response among HBV genotypes and discuss the role of precore or core promoter mutations in response to antiviral therapy.     

乙肝病毒表面抗原阳性产妇所生婴儿乙型肝炎疫苗无/弱应答情况及影响因素分析

  目的   探讨乙型肝炎（乙肝）病毒表面抗原（HBsAg）阳性母亲所生婴儿对乙肝疫苗无/弱应答发生情况以及影响因素。  方法   对2018—2021年在广州市南沙区HBsAg阳性母亲所生的全部婴儿进行追踪随访,对随访成功的婴儿检测外周血乙肝病毒血清标志物,并采用结构化问卷收集相关的可能影响婴儿乙肝疫苗无/弱应答的因素。  结果   在婴儿7～12月龄进行电话召回,共招募随访640对HBsAg阳性产妇及所生婴儿,2名（0.31%）婴儿感染乙肝病毒,婴儿对乙肝疫苗无/弱应答发生率为2.81%（18/640）,其中无应答发生率为0.31%（2/640）,弱应答发生率为2.50%（16/640）。 因素分析发现,HBsAg阳性产妇所生婴儿对乙肝疫苗无/弱应答与强应答组在母亲婚姻状况、文化程度、是否为HBeAg阳性、孕期HBV DNA情况、分娩方式、分娩胎龄、出生体重、婴儿性别、是否12 h内接种首剂乙肝疫苗以及乙肝免疫球蛋白方面差异均无统计学意义（P>0.05）。 HBeAg阳性或孕期HBV DNA高水平母亲,47.65%（81/170）孕期进行了抗病毒治疗,其所生婴儿12 h内接种首剂乙肝疫苗、乙肝免疫球蛋白的比例略高于HBeAg阴性或孕期HBV DNA低水平母亲所生婴儿,两组婴儿乙肝疫苗无/弱应答发生率差异无统计学意义（P>0.05）。  结论   随着消除乙肝母婴传播工作的逐步推进,HBsAg阳性产妇所生婴儿发生母婴传播、乙肝疫苗无/弱应答较以往研究明显降低。 今后应进一步强化首剂乙肝疫苗、乙肝免疫球蛋白接种时限,及对孕期HBV DNA高水平或HBeAg阳性孕妇知情告知后进行抗病毒治疗。     

乙型肝炎病毒基因型与恩替卡韦抗病毒疗效关系

目的探讨乙型肝炎病毒（HBV）基因型与恩替卡韦抗病毒治疗疗效的关系。方法应用聚合酶链反应（PCR）-微板核酸分子杂交-酶联免疫吸附测定（ELISA）法检测103例慢性乙型肝炎（CHB）患者HBV的基因型,给予恩替卡韦（O．5mg／d）抗病毒治疗48周;治疗前、治疗后分别检测肝功能、乙型肝炎5项和HBVDNA定量,同时注意药物不良反应。结果103例CHB患者中感染B基因型者34例,感染C基因型者69例。治疗48周,感染B基因型和C基因型患者丙氨酸转氨酶（ALT）复常、HBVDNA转阴、乙型肝炎病毒e抗原（HBeAg）消失和HBeAg／乙型肝炎病毒e抗体（HBeAb）血清转换差异均无统计学意义（P〉0．05）。结论HBV基因型不影响恩替卡韦抗病毒疗效。     

大三阳孕妇产婴疫苗免疫分析

目的了解大三阳孕妇所生婴儿6年后乙肝疫苗免疫情况。方法大三阳孕妇所生婴儿出生后、1个月和6个月注射乙肝疫苗;随访6年后用ELISA法检查乙肝两对半。结果未接种乙肝疫苗的大三阳孕妇新生儿6年后乙肝表面抗原阳性率90%(9/10),乙肝表面抗体阳性率10%(1/10);接种乙肝疫苗的大三阳孕妇新生儿6年后乙肝表面抗原阳性率5%(1/20),乙肝表面抗体阳性率80%(16/20)。结论新生儿接种乙肝疫苗后大大降低了乙肝表面抗原阳性率。     

HBV感染者孕妇所生婴儿HBV血清学标志研究

目的为了预防HBV的母婴传播。方法对HBV感染孕妇在不同孕期进行被动免疫干预后,检测新生儿的HBV感染情况。结果新生儿抗HBs阳性94／124例,抗HBc阳性42／124例,抗Hbe阳性9／124例,HBSAg阳性7倒;在单纯的抗HBs阳性中被动免疫组68／75例,在单纯的抗HBc阳性事被动免疫组13／23例。结论对HBV感染孕妇进行产前注射抗HBs高效免疫球蛋白被动免疫预防HBV母婴传播,是一个比较好的阻断母婴传播的方法。     

Hepatitis B virus genotypes and response to antiviral therapy

Hepatitis B virus (HBV) infection is an important health problem worldwide. The virus has been classified according to 8 genotypes (A-H) based on sequence divergence. Most genotypes have specific geographic distributions; genotypes A and D are prevalent in Western Europe and North America, and genotypes B and C are prevalent in East Asia and Oceania. Currently accepted treatment for chronic hepatitis B includes interferon alpha, or the nucleoside/nucleotide analogues lamivudine and adefovir. The impact of HBV genotypes on response to antiviral therapy has been studied. HBV genotypes D and C are associated with a lower rate of favorable response to interferon alpha therapy than genotypes A and B, respectively. A study in Germany suggested that the rate of resistance to lamivudine was higher in patients with HBV genotype A infection than in patients with genotype D infection. No difference in the risk of lamivudine resistance is found between patients with genotype B and patients with genotype C. In patients with genotype C infection, however, virological response is worse during lamivudine therapy, and is also less durable after the discontinuation of therapy than in patients with genotype B infection. Determining the genotype could be helpful for predicting the outcome of antiviral therapy in patients with chronic hepatitis B.     

Influence of hepatitis B virus genotypes on the response to antiviral therapies

Hepatitis B virus (HBV) has been classified into eight genotypes (A-H) based on genome sequence divergence. Genotypes of HBV have distinct geographical distributions, and two genotypes account for most HBV worldwide. Hepatitis B e antigen expression lasts longer and liver disease is more severe with graver outcomes in carriers of genotype C than B in Asia. Accumulating lines of evidence indicate a better response to interferon and lamivudine in patients with chronic hepatitis B who are infected with genotype B rather than C. The therapeutic response may differ, however, in patients infected with HBV of the same genotype. For example, the response to lamivudine is poorer in patients infected with subtype Ba, which contains a recombination with genotype C, than in those with subtype Bj without such a recombination. Influence of genotypes on therapeutic response needs to be examined in patients infected with the other genotypes, particularly in those with genotype A or D infection.     

HBV相关中和抗体在慢性乙型肝炎抗病毒治疗中的研究进展

HBV感染不仅是一项重要的全球性公共卫生问题,也是我国正在面临的一项重要挑战。虽然现在已有针对HBV的疫苗并且其接种普及率也在逐年提高,但仍然有很多的乙型肝炎患者亟待治疗。中和抗体作为HIV一项重要的治疗方法同样在HBV的治疗研究领域被寄予厚望。目前针对HBV相关中和抗体的研究主要包括G12、Bc1.187、H017、...     

Discontinuation of antiviral therapy in chronic hepatitis B patients

Nucleos(t)ide analogs (NUC) are the first-line therapy for patients with chronic hepatitis B (CHB) recommended by most current guidelines. NUC therapy decreases progression of liver disease, reduces the risk of liver-related complications, and improves the quality of life of patients with CHB. Although indefinite or long-term NUC therapy is usually recommended, this strategy raises several concerns, such as side-effects, adherence, costs, and patient willingness to stop therapy. Recent data showed the feasibility, efficacy, and safety of stopping antiviral therapy in carefully selected CHB patients, leading to its incorporation in international guidelines. Patients who discontinue NUC have a higher likelihood of hepatitis B surface antigen (HBsAg) loss compared to patients who continue on therapy. Recommendations pertaining endpoints allowing safety discontinuation of NUC therapy differ among international guidelines. For hepatitis B e antigen (HBeAg)-positive patients, durable HBeAg seroconversion is considered an acceptable treatment endpoint. For HBeAg-negative patients, some guidelines propose undetectability hepatitis B virus DNA for at least 2 or 3 years, while others consider HBsAg loss as the only acceptable endpoint. CHB patients who stop therapy should remain under strict clinical and laboratorial follow-up protocols to detect and manage relapses in a timely manner. No reliable predictor of relapse has been consistently identified to date, although quantitative HBsAg has been increasingly studied as a reliable biomarker to predict safe NUC discontinuation.