国产基因工程干扰素α1治疗慢性乙型肝炎的临床研究

２２５例慢性乙型肝炎分三组治疗，Ａ和Ｂ组７４例配对随机用干扰素α１及安慰剂双盲对照观察，Ｃ组１５１例为干扰素α１４０微克连用三个月，ＨＢｅＡｇ、ＨＢＶ－ＤＮＡ、ＨＢｅＡｇ和ＨＢＶ－ＤＮＡ双转阴率及抗ＨＢｅ转阳率分别为４０．５％、５７．１％、３９．３％及２９．７％，与对照组差异有非常显著性（Ｐ＜０．０１）。扩大治疗组结果与Ａ组相似，均明显优于对照组。治疗组随访半年和一年ＨＢｅＡｇ及ＨＢＶ－ＤＮＡ转阴率与治疗结束时相似，表明有较持久的效果。     

拉米夫定治疗HBeAg阴性的慢性HBV感染近期临床观察

观察和评价拉米夫定治疗ＨＢｅＡｇ阴性慢性ＨＢＶ感染的近期疗效。ＨＢｅＡｇ阴性／ＨＢＶ ＤＮＡ阳性的慢性ＨＢｖ感染者２６例（包括１１例乙肝肝硬化），ＨＢｅＡｇ阳性／ＨＢＶ　ＤＮＡ阳性的慢性ＨＢＶ感染者３０例（包括１０例乙肝肝硬化），均以拉米夫定治疗６个月后进行疗效评价，并继续观察５－１６个月。两组的ＡＬＴ／ＡＳＴ复常率分别为８４．７％／８８．５％和８６．７％／８６．７％（Ｐ＞０．０５），肝硬化患者Ｃｈｉｌｄ－Ｐｕｇｈ积分均明显下降，ＨＢＶ　ＤＮＡ全部阴转。ＨＢｅＡｇ阳性组３例发生ＹＭＤＤ变异，ＨＢｅＡｇ阴性组无１例变异。拉米夫定对于ＨＢｅＡｇ阴性／ＨＢＶ　ＤＮＡ阳性者，同样是十分安全有效的抗病毒治疗药物。ＨＢｅＡｇ阴性者的耐药发生率可能低于ＨＢｅＡｇ阳性者。     

拉米夫定、治肝灵冲剂联合治疗慢性乙型肝炎近期疗效研究

研究单用拉米夫定（３－ＴＣ）及联合应用中药治肝灵冲剂对慢性乙型肝炎（ＣＨＢ）的治疗作用，探讨两者联合治疗的近期疗效和安全性。５０例ＣＨＢ患者随机分为Ａ，Ｂ两组，Ａ组采用３－ＴＣ和治肝灵冲剂联合治疗；Ｂ组单用３—ＴＣ，疗程均为６个月，治疗前、治疗２周、４周、８周、１２周、１６周，２０周、２６周分别检测ＨＢＶ标志、肝功能，血清学指标，肾功能，并记录治疗期间临床和实验室检查发生的一切不良事件。治疗２６周后Ａ组血清ＨＢｅＡｇ转阴率６４．０％（１６／２５）．明显高于Ｂ组１６．０％（４／２５）Ｐ＜０．０１． Ａ组与Ｂ组分别有４例（１６．０％），２例（８．０％）实现ＨＢｅＡｇ血清转换。Ｐ＞０．０５。转阴患者未发现ＨＢＶ前Ｃ区变异株。Ａ组和Ｂ组ＨＢＶＤＮＡ转阴例数分别为２４（９６．０％）和２３（９２．０％）Ｐ＞０．０５。治疗结束时Ａ组和Ｂ组ＡＬＴ的复常率分别为８８．０％（２２／２５）、６４．０％（１６／２５），Ｐ＜０．０５。采用３－ＴＣ与治肝灵冲剂联合治疗ＣＨＢ，短期疗效明显优于单一用药组，且副作用少，是安全、有效的治疗ＣＨＢ的方案。     

甲基班蝥胺治疗慢性乙型肝炎的临床研究

应用甲基斑蝥胺治疗慢性乙型肝炎（下称乙肝）５２例。结果ＨＢｓＡｇ阴转１３例，占２５．０％；ＨＢｅＡｇ阴转３５例，占６７．３％；抗ＨＢ ｅ阳转１９例，占３６．５％，以ＰＣＲ技术检查血清和外周血单核细胞中的ＨＢＶ－ＤＮＡ，治疗后阴转分别为３３．３％（１０／３０例）和６５．７％（２３／３５例）。与对照组相比上述５项结果均有显著性差异（Ｐ〈０．０１）。部分病例经过６￣１２个月的随访，疗效基本保持不变。显示     

抗HCV阳性慢性肝病患者HBV感染及前C／C区基因变异

探讨ＨＢＶ基因变异在ＨＢｓＡｇ阴性抗ＨＣＶ阳性慢性肝病中的意义。方法用巢式聚合酶链反应（ＰＣＲ）与限制片段长度多态性相结合，对５６例慢性肝病患者６例ＨＢｓＡｇ阴性抗ＨＣＶ阳性（Ａ组）．１９例ＨＢｓＡｇ阳性抗ＨＣＶ阳性（Ｂ组）及３１例单独ＨＢＶ成染（Ｃ组）进行前Ｃ区密码２８终止变异（Ａ８３）和Ｃ区密码９７异亮氨酸亮氨酸变异（Ｌ９７）分析。结果Ａ组和Ｂ组Ａ８３和Ｌ９７变异检出率分别为３３％和４２％显著低于Ｃ组８１％（Ｐ值＜０．００１）：而Ａ组和Ｂ组间无统计学差异（Ｐ值＞０．０５）。结论ＨＢＶ和ＨＣＶ双重感染ＨＢｓＡｇ阴性与Ａ８３和Ｌ９７变异无相关。     

LAK细胞治疗慢性乙,丙型肝炎疗效及免疫机制研究

报道应用自体ＬＡＫ细胞回输治疗１１０例慢性乙型肝炎（乙肝）和２０例慢性丙型肝炎（丙肝）的结果。疗程结束时慢性乙肝治疗组ＨＢｅＡｇ阴转率、抗－ＨＢｅ阳转率和ＨＢｖＤＮＡ阴转率分别为４６，４％、３５．５％和４８．２％，与对照组相比明显提高（Ｐ均〈０．００５）；２ｏ例慢性丙肝经治疗后抗－ＨＣＶ阴转２例（１０％），ＨＣＶＲＮＡ阴转４例（２０％），而对照组维持不变。进而对ＬＡＫ治疗的免疫机制进行探讨，结果发现ＬＡＫ治疗后ＣＡＨ患者ＣＤ＋４阳性率、ＣＤ＋４／ｃＤ＋８比值均增高（Ｐ＜０．０５），外周血单个核细胞膜白细胞介素－２受体（ｍＩＬ－２Ｒ）和血清中可溶性白细胞介素－２受体（ｓＩＬ－２Ｒ）的水平也明显升高（Ｐ＜０．０１）。     

无症状HBsAg携带者血清标志物的动态观察

本文对临床诊断的３９３例无症状ＨＢｓＡｇ携带者按病理改变分为正常组、无症状携带者组、不典型肝炎组、慢迁肝组、慢活肝组，并分别观察血清标志物的变化３６￣４２个月。发现慢迁肝组ＨＢｅＡｇ、ＨＢＶ－ＤＮＡ阳性率降低（Ｐ〈０．０１），慢活肝组ＨＢｅＡｇ阳性率降低（Ｐ〈０．０５），二组的ＨＢｓＡｇ滴度以波动多见，其余各组ＨＢｓＡｇ阳性率降低（Ｐ〉０．０５），抗ＨＢｅ阳性率增加（Ｐ〉０．０５）。提示，无症状Ｈ     

自体与异体LAK细胞治疗慢性肝炎130例

目的对ＬＡＫ细胞治疗慢性肝炎作客观估价．方法治疗与对照组均口服维生素，肌注肝炎灵．治疗Ａ组加回输自体ＬＡＫ细胞，每周２次，６周为１个疗程；Ｂ组每周输注异体ＬＡＫ细胞悬液１次，５次为１疗程．结果ＬＡＫ细胞治疗慢性肝炎能使部分患者ＨＢｅＡｇ及ＨＢＶＤＮＡ阴转．治疗结束时ＨＢｅＡｇ阴转率Ａ组为４７５％，Ｂ组为５８０％；而对照组Ｃ为１５０％（Ｐ＜００５）．ＨＢＶＤＮＡ阴转率Ａ组为４５０％，Ｂ组为６６０％，而对照组Ｃ为１１８％，（Ｐ＜００５％）．结论ＬＡＫ细胞治疗对ＨＢＶ复制有明显抑制作用．异体ＬＡＫ组的ＨＢｅＡｇ及ＨＢＶＤＮＡ阴转率高于自体ＬＡＫ组．     

PCR直接法检测HBsAg阴性肝病的价值

目的研究ＨＢｓＡｇ阴性肝病患者和自然人群中乙肝病毒（ＨＢＶ）携带者。方法采用ＤＮＡＰＣＲ直接法测定急、慢性肝炎，肝硬变和单项ＡＬＴ增高者共２３１例ＨＢｓＡｇ阴性患者中ＨＢＶＤＮＡ，２４０例ＨＢＶ标志阴性的自然人群对照。结果检出率在患者组和对照组分别为３３．７％（７８／２３１）和１１．５％（２８／２４０），Ｐ＜０．０１。单项ＡＬＴ增高组最高，达６６．７％（１０／１５），其他依次为慢肝组（ＣＨ）４１．９％（１３／３１）、肝硬变组（ＬＣ）３０．７％（５２／１６９）和急肝组１８．７％（３／１０）。单项ＡＬＴ增高组与ＬＣ、急肝组有显著差异（Ｐ＜０．０１）。结论在ＨＢｓＡｇ阴性的肝病患者和自然人群中均有ＨＢＶ携带者     

丁咪替丁治疗慢性乙型肝炎

７０例慢性乙型肝炎患者经服西咪替丁治疗，总疗程６个月。其中ＡＬＴ复常率８２．９％，ＨＢｓＡｇ阴转率１７．１％，ＨＢｅＡｇ阴转率６０％明显优于同期对照（Ｐ〈０．０５）。提示Ｃｉｍ能抑制ＨＢＶ复制，从而使部分患者临床和肝功能均改善。     

Chronic hepatitis B

Opinion statement Interferon alpha, lamivudine, and adefovir are the three drugs currently approved for the treatment of chronic hepatitis B virus (HBV). There are pros and cons associated with the use of each drug. Individualization of therapy, based upon factors such as patient comorbidities, response to prior therapies, and stage of disease, is recommended. Patients with abnormal liver enzymes, indices of active viral replication (HBV DNA positive ± hepatitis B early antigen [HB_eAg] positive) or evidence of necroinflammatory activity on liver biopsy, and compensated liver disease are potential candidates for treatment with interferon, lamivudine, or adefovir. Patients with abnormal liver enzymes, indices of active viral replication (HBV DNA positive ± HB_eAg positive), and decompensated liver disease are candidates for treatment with lamivudine or adefovir. Consideration of liver transplantation should occur concurrently. Interferon alpha treatment results in hepatitis B surface antigen [HB_eAg] loss and sustained suppression of HBV DNA replication in 30% to 40% of treated patients. Loss of HBsAg occurs in nearly 10% of patients and a higher than expected frequency of HBsAg loss occurs long-term. The main limitation of therapy is the side effects and the need for parenteral administration. Additionally, interferon therapy is not applicable to all patient groups. Lamivudine achieves HB_eAg seroconversion in 15% to 20% of patients treated for 12 months, but (HBsAg) loss is rare. Reduction in HBV DNA to undetectable levels (by hybridization assay) during treatment is nearly universal, and histologic improvement is seen in about 55% of patients. The main limitation of lamivudine therapy is the development of drug resistance, which occurs in 20% of patients after 12 months and increases with duration of therapy (55% at 3 years). Adefovir achieves HB_eAg seroconversion in 12% of patients treated for 12 months, but HBsAg loss is rare. An average 3.5 log reduction in HBV DNA levels is and histologic improvement occurs in 50% to 60% of patients. It is effective against both wild-type and lamivudine-resistant HBV. The risk of drug resistance is low and estimated to be approximately 2% to 3% after 2 years of treatment. Several new antiviral agents are currently under evaluation in clinical trials. In addition, there are two drugs (tenofovir and emtricitabine) that have been approved for HIV infection and that have anti-HBV activity. In the future, combination therapy for chronic HBV infection can be anticipated. Utilization of two or more anti-HBV drugs would be predicted to enhance efficacy and reduce the likelihood of emergence of drug resistance.     

Chronic hepatitis B

Opinion statement  

Chronic hepatitis B infection

The management of chronic hepatitis B virus (HBV) infection requires understanding the natural history of the disease as well as the risks, benefits, and limitations of the therapeutic options. This article covers the principles governing when to start antiviral therapy, discusses recent advances using hepatitis B surface antigen quantification to better define various phases of infection, describes the use of HBV core, precore, and viral genotyping as well as host IL28B genotyping to predict response to interferon therapy, and reports on the management of HBV in 3 special populations (pregnancy, postliver transplantation, and in the setting of chemotherapy or immunosuppression).     

B Cell-mediated Humoral Immunity in Chronic Hepatitis B Infection

B cell-mediated humoral immunity plays a vital role in viral infections, including chronic hepatitis B virus (HBV) infection, which remains a critical global public health issue. Despite hepatitis B surface antigen-specific antibodies are essential to eliminate viral infections, the reduced immune functional capacity of B cells was identified, which was also correlated with chronic hepatitis B (CHB) progression. In addition to B cells, T follicular helper (Tfh) cells, which assist B cells to produce antibodies, might also be involved in the process of anti-HBV-specific antibody production. Here, we provide a comprehensive review of the role of various subsets of B cells and Tfh cells during CHB progression and discuss current novel treatment strategies aimed at restoring humoral immunity. Understanding the mechanism of dysregulated B cells and Tfh cells will facilitate the ultimate functional cure of CHB patients.     

Chronic hepatitis B: treatment alert

Abstract: Chronic hepatitis B (CHB) is a serious global health concern, particularly in the Asia‐Pacific region. New information on the clinical management of CHB is emerging rapidly, requiring that physicians be alerted to updated treatment recommendations. The ACT‐HBV Asia‐Pacific Steering Committee members, composed of experts in hepatitis B from throughout the Asia‐Pacific region, reviewed and discussed new clinical data as reported in the literature or presented at recent international congresses, and recommended that physicians be alerted to updated treatment recommendations. Hepatitis B e antigen (HBeAg)‐positive patients with HBV DNA levels of ≥20 000 IU/ml (≥10⁵ copies/ml) and elevated alanine aminotransferase levels should be considered for treatment. It is suggested that HBV DNA≥2000 IU/ml (≥10⁴ copies/ml) is the more appropriate threshold for the treatment of HBeAg‐negative patients. Lamivudine, adefovir dipivoxil, interferon α‐2b, thymosin α‐1, and, most recently, entecavir, and pegylated interferon α‐2a are licensed for the management of CHB. The treatment recommendations from the 2005 Asian‐Pacific Consensus Statement on the Management of Chronic Hepatitis B have been updated to incorporate these new therapeutic options. A summary of treatment recommendations for special patient populations is also included.