IFN-α2b联合胸腺肽治疗慢性乙型肝炎临床观察

我们自 1999年 5月以来 ,用ＩＦＮ α2ｂ(天津华立达生物工程有限公司生产 )与胸腺肽 (浙江省医学科学院制药厂生产 )联合治疗慢性乙型肝炎 5 2例 ,取得较理想疗效 ,现报道如下。资料与方法10 2例均为我院住院及门诊患者 ,临床诊断符合 1995年第5届全国传染病与寄生虫病会议诊断标准。治疗组 5 2例 ,男40例 ,女 12例 ,年龄 16～ 49岁 ,平均 2 9.6岁 ,病程 6个月～ 15年 ,平均 3 .5年。对照组 5 0例 ,男 37例 ,女 13例 ,年龄 18～ 40岁 ,平均 2 5 .5岁。病程 6个月～ 12年 ,平均 2 .2年。两组病例均为慢性乙型肝炎轻度或中度 ,在性别、年龄、…     

干扰素联合胸腺肽治疗慢性乙型肝炎长期随访研究

目的 评价a干扰素(IFN-a）联合胸腺肽治疗慢性乙型肝炎（CHB）的近、远期疗效和安全性,探讨两进行联合治疗的协同作用。方法 215例HBV DNA及HBeAg阳性的CHB患者随机分为甲、乙两组,甲组采用IFN-a和胸腺肽联合治疗,乙组单用IFN-a,疗程均为6个月。治疗结束后随访24个月。观察两组肝功能和乙型肝炎病毒标志（HB-VM及HBV DNA）的变化情况和不良反应。结果 治疗结束时,两组临床症状均明显改善。甲组中81例（63.3%）ALT恢复正常,而乙组仅43例（49.4%）正常,两组有显著性差异;甲组有70%HBV DNA阴转,59.4%HBeAg阴转,56.3%为近期完全应答（ALT复常,HBV DNA及HBeAg均阴转）,乙组分别为63.2%,48.3%和46.0%,两组无显著性差异。治疗结束后24个月,甲组有66.4%ALT恢复正常,68.8%HBV DNA阴转,66.4%HBeAg阴转,64.1%为持续完全应答;而乙组则分别为28.7%,36.8%,37.9%和26.4%,两组有非常显著性差异。治疗结束时有生化学和（或）病毒学应答的病例,随访期间甲组有23.5%ALT又异常,24.4%HBV DNA再转阳,14.5%HBeAg再转阳,乙组则分别为48.8%,47.3%和35.7%,乙组生化学和病毒学复发率显著高于甲组,具有非常显著性差异。治疗结束时无应答的病例中,随访期间甲组有48.9%ALT复常,52.6%HBV DNA阴转,38.5%HBeAg阴转,而乙组分别为6.8%,9.4%和13.3%,甲组的生化学和病毒学滞后应答率显著高于乙组,两组具有非常显著性差异。治疗过程中,甲组出现与IFN-a治疗相关的初期不良反应。结论 IFN-a与胸腺肽联合治疗CHB具有明显的协同作用,可明显改善肝功能,抗病毒效果好,明显优于单用IFN-a组,大大提高了IFN-a的远期疗效,使复发率明显降低,是CHB患者安全、有效的治疗方法。     

苦参素联合干扰素治疗慢性乙型肝炎患者49例疗效观察

2003年7月-2004年7月,我院应用国产基因工程干扰素（IFNα-2a）联合苦参素治疗慢性乙型肝炎患者49例,取得一定疗效,现报告如下。     

慢性乙型肝炎的联合抗病毒治疗

全球约有3.5亿人感染乙型肝炎病毒(HBV).目前抗HBV的主要药物有干扰素(IFN)、拉米夫定(LAM)和阿德福韦(ADV)等,现就有关药物的联合治疗作一简述.     

胸腺肽α1联合拉米夫定治疗慢性乙型肝炎

目的　探讨胸腺肽α1(Tα1)和拉米夫定 (LAM )联合治疗慢性乙型肝炎的长期疗效和安全性。方法　按随机对照原则选择 80例HBVDNA、HBeAg阳性的慢性乙型肝炎患者 ,按 1∶1随机分配进入单一接受拉米夫定治疗组 (LAM组 )和拉米夫定联合治疗组 (LAM +Tα1组 )。结果　治疗5 2周时 ,LAM +Tα1组HBeAg血清转换率 (5 1.4 % ,18/35 )明显高于LAM组 (5 .4 % ,2 /37) ,P <0 .0 1。停药 1年后 ,持续的HBeAg血清转换率分别为 4 2 .9% (15 /35 )和 8.1% (3/37) ,P <0 .0 1。治疗过程中 ,两组HBVDNA定量明显下降 ,联合治疗组下降更显著 ,治疗后 ,两组的丙氨酸转氨酶(ALT)复常率基本一致 ,达 77.1% (2 7/35 )和 6 7.6 % (2 5 /37) ,但停药后LAM组仅有 18.9%持续正常 ,明显低于联合治疗组。治疗 5 2周 ,联合治疗组完全应答率 (42 .9% )明显高于LAM组 (8.1% ) ,停药后 1年 ,持续应答率分别为 6 0 .0 % (2 1/35 )和 18.9% (7/37) ,P <0 .0 1。治疗过程中LAM +Tα1组未发现HBV前C区变异株。LAM组有 10例 (2 7.0 % )发生YMDD变异株 ,联合组仅有 1例。治疗后肝组织炎症坏死程度明显地改善 ,肝纤维化程度降低 ,HBsAg、HBcAg的表达明显减少 ,治疗过程无明显的不良反应。结论　Tα1与LAM联合治疗慢性乙型肝炎 ,不良反应少 ,疗效优     

苦参素联合西维尔治疗慢性乙型肝炎

我们1999年6月-2001年9月应用苦参素联合西维尔治疗慢性乙型肝炎(简称慢乙肝),并设干扰素对照组进行观察。 1 临床资料 1.1 一般资料慢乙肝病例共102人,其中男性78人,女性24人,年龄17～67岁,平均37.2岁,均有大三阳(HBsAg、HBeAg、HBcAb),HBV DNA阳性,ALT高于正常2～4倍,SB低于34mmol/L,病程3～15年,无甲型肝炎病毒、丙型肝炎病毒合并或重叠感染,无严重心、肾、脑并发症及糖尿病、甲亢,随机分为2组。2组患者年龄、性别、病情及病程均具可比性(P>0.05)。治疗组应用博尔泰力(氧化苦参碱)400mg,肌肉注射,     

胸腺肽α1联合干扰素治疗慢性乙型肝炎临床分析

目的研究胸腺肽α1联合干扰素对慢性乙型肝炎（CHB）的治疗作用。方法经临床诊断为CHB（轻、中度）并乙肝病毒复制指标阳性患者68例，随机分为2组，胸腺肽α1加干扰素组和单用干扰素组，疗程6个月。结果联合治疗组肝功能复常与对照组差异无显著性。病毒复制指标阴转率差异有显著性（P〈0．05）。结论胸腺肽α1、干扰素为治疗乙型肝炎较为有效的药物，两者合用有相加或协同作用，为治疗CHB较为理想的方案。     

慢性乙型肝炎抗病毒治疗的进展

由于乙肝病毒(HBV)是肝炎发生和发展的基础．因此清除病毒是慢性乙型肝炎治疗的关键。消除病毒的策略有2种：清除感染了HBV的肝细胞和抑制(或杀灭)病毒本身。     

乙型肝炎疫苗混合胸腺肽联合免疫球蛋白治疗慢性乙型肝炎36例

我国慢性HBV携带者众多，因其具有较强的传染性及演变为慢性肝炎甚至肝硬化的危险，无论是携带者还是医师，都在积极寻找病毒转阴的方法。我们于2004年6月至9月使用人乙型肝炎免疫球蛋白、乙型肝炎疫苗混合胸腺肽对36例HBV携带者进行治疗，现将治疗结果报道如下。     

拉米夫定联合乙型肝炎疫苗治疗慢性乙型肝炎的疗效观察

由于乙型肝炎病毒(HBV)复制过程较为复杂，单一应用抗HBV药物欠理想，选用两种或两种以上具有抗病毒，免疫调节或免疫增强剂药物联合治疗很有必要。拉米夫定联合干扰素被公认对抑制HBV复制有肯定疗效，但疗程长，价格贵，多数病人因经济受限而不能采用。我们1997—03始在临床上应用拉米夫定联合乙型肝炎疫苗(以下简称乙肝疫苗)治疗慢性乙型肝炎(以下简称慢性乙肝)，并与同期单用干扰素的病例对照比较，取得较好的疗效，现总结报告如下。     

Combination Therapy for Chronic Hepatitis B: Current Indications

Hepatitis B infection remains a major public health problem globally and in the United States, with significant use of healthcare resources. Several therapeutic agents active against viral and host targets are currently available for its treatment. The success of combination therapy in HIV infection, which has similarities to hepatitis B in both therapeutic targets and treatment options, stimulated studies on the efficacy and safety of various combinations of available drugs in the treatment of hepatitis B infection. In this review, we analyze the current role of combination therapy in chronic hepatitis B infection.     

拉米夫定和泛昔洛韦联合治疗慢性乙型肝炎

背景现有的抗病毒药物单用均难以完全清除乙型肝炎病毒(HBV)感染。体外研究证明,拉米夫定(LMD)和Penciclovir[泛昔洛韦(FCV)的活性代谢物]联合应用对HBV复制具有相加或协同抑制作用。目的研究LMD和FCV联合疗法对慢性乙型肝炎感染的疗效。方法21例慢性乙型肝炎患者在联合治疗前曾接受6个月以上的LMD治疗,但均未取得改善。所有患者均为血清乙型肝炎表面抗原(HBsAg)阳性,具有高水平HBVDNA和丙氨酸转氨酶(ALT),17例乙型肝炎e抗原(HBeAg)阳性。12例HBeAg阳性患者的诊断得到组织学证实。联合用药方案为治疗期LMD100mgqd+FCV500mgtid口服4个月;随访期(5～10个月)单用LMD,剂量同前。结果21例患者的血清HBVDNA水平在治疗前为1×10819±0.58copies/ml,治疗期末为1×104.55±1.18copies/ml,随访期为1×105.25±1.82copies/ml(P＜0.01);ALT水平从联合治疗前的225U/L±110U/L降至治疗期末的79U/L±50U/L和随访期的81U/L±48U/L(P＜0.01)。17例HBeAg阳性患者中,8例(47.1％)发生HBeAg/抗HBe血清转换;与此同时,血清ALT均正常化,HBVDNA降至1×104copies/ml以下(P＜0.01)。4例HBeAg阴性患者中,3例HBVDNA降至1×104copies/ml以下,ALT同时降至正常或明显降低。共有2例患者在随访期复发,其中1例HBeAg再次转为阳性,但HBVDNA和ALT均低于治疗前水平。10例接受肝活检复查的患者中,分别有8例(80％)和4例(40％)肝脏炎症活动度和纤维化程度得到改善(P＜0.05),无一例病变加重。结论LMD和FCV有协同或相加性抗HBV作用,可作为慢性乙型肝炎可供选择的治疗方法。     

Efficacy of Entecavir and Adefovir Combination Therapy for Patients with Lamivudine- and Entecavir-Resistant Chronic Hepatitis B

Background  

The optimal treatment of patients with chronic hepatitis B (CHB) who develop resistance to both lamivudine (LMV) and entecavir (ETV) after sequential monotherapy of LMV and ETV remains little known.     

Combination Therapy in Liver Transplant Recipients with Hepatitis B Virus Without Hepatitis B Immune Globulin

Introduction: Conventional therapy to prevent HBV recurrence in liver transplant (LTx) recipients consists of Hepatitis B Immune Globulin (HBIg). The aim of this review is to investigate the safety and efficacy of converting HBIg and LAM therapy to ADV and LAM therapy. Methods: A retrospective review involving all liver transplant patients with HBV maintained on HBIg and LAM therapy. Results collected included: gender, age, HBV serological and DNA status (COBAS AmpliScreen PCR-based testing). Serologic testing was done every three months. Patients were followed for drug reactions, therapy compliance, and immune suppression compliance. A cost benefit analysis was done for drug comparisons using United States currency values. Results: Patient demographics included: Male (n=6), Female (n=4), mean age 44 years (range 33 to 65). The mean length of follow up since therapy conversion (from HBIg and LMV to ADV and LMV) was 21 months (range 16 to 25 months). Serological status at time of conversion revealed that DNA status remained negative in all patients, HBsAg negative in 10/10, HB eAg (+) (5/10) and HBeAb (+)(5/10). None of the patients experienced an increase in transaminases while on dual ADV and LAM therapy. All patients were maintained on immune suppression monotherapy (tacrolimus) at 7–9 ng/mL. All patients reported compliance with the dual therapy and that they experienced no drug related side effects. Mean yearly costs for ADV and LAM was 7,235.00 United States dollars (range 6,550.00 to 8,225.00); while mean monthly costs for HBIg and LAM; 9225.00 (range 7205.00 to 12005.00). Conclusion: The above results demonstrate beneficial effects of ADV and LAM in place of the current standard of HBIg and LAM therapy. Safety and short term results show nucleoside therapy is adequate at preventing HBV viral recurrence. Lastly, the economic benefit for ADV and LAM vastly outweighed the HBIg and LAM group.     

Current Trend in Antiviral Therapy for Chronic Hepatitis B

Since active hepatitis B virus (HBV) replication is the key driver of hepatic necroinflammation and disease progression, the treatment aim of chronic hepatitis B (CHB) is to suppress HBV replication permanently to prevent hepatic decompensation, liver cirrhosis and/or hepatocellular carcinoma and prolong survival. Currently, pegylated interferon (Peg-IFN), entecavir (ETV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) are the first-line drugs of choice. Peg-IFN therapy has been used rarely due to its subcutaneous injection and significant side effect profile. Once daily oral ETV, TDF and TAF can suppress HBV DNA profoundly but have no direct action on cccDNA of the HBV-infected hepatocytes, hence continuing long-term therapy is usually needed to maintain HBV suppression, but the ultimate goal of HBsAg loss was rarely achieved (10 year 2%). In addition, long-term NUC therapy comes with several concerns such as increasing cost, medication adherence and loss-to-follow-up. Studies, mainly from Taiwan, have shown that finite NUCs therapy of two to three years in HBeAg-negative patients is feasible, safe and has a great benefit of much increasing HBsAg loss rate up to 30%/5 year. These have led an emerging paradigm shift to finite NUC therapy in HBeAg-negative patients globally. However, off-NUC relapse with hepatitis B flares may occur and have a risk of decompensation or even life-threatening outcomes. Therefore, proper monitoring, assessment, and retreatment decisions are crucial to ensure safety. Ideally, retreatment should be not too late to ensure safety and also not too early to allow further immune response for further HBsAg decline toward HBsAg loss. Assessment using combined HBsAg/ALT kinetics during hepatitis flare is better than biochemical markers alone to make a right retreatment decision. The strategy of finite NUC therapy has set a benchmark of high HBsAg loss rate to be achieved by the new anti-HBV drugs which are under preclinical or early phase study.     

慢性乙型肝炎拉米夫定治疗后的HBeAg早期血清转换

目的:分析拉米夫定与中成药五灵丸治疗慢性乙型肝炎的临床疗效。方法:对25例成人慢性乙型肝炎患者进行为期1年的拉米夫定的开放性临床治疗,头3个月加用五灵丸。治疗期间定期进行血清ALT、HBeAg、抗-HBe及HBV DNA检测,停药后随访半年。结果:治疗期间共有12例患者(48％)发生HBeAg转阴,并出现抗-HBe;在HBeAg血清转换后的2～4w,8例患者抗-HBe随后消失;在治疗的头3个月随着HBV DNA水平下降及消失(<420copies/ml),所有患者ALT水平逐渐降至正常。结论:治疗头3个月是应用拉米夫定治疗患者HBeAg发生血清转移的关键。这种早期转换的可能解释之一是慢性乙肝患者存在对拉米夫定特别敏感的亚型或种群。