干扰素联合核苷（酸）类似物治疗慢性乙型肝炎的疗效观察

目的观察干扰素（IFN）与核苷（酸）类似物联合治疗慢性乙型肝炎的疗效。方法选择慢性乙型肝炎病例207例,分别予聚乙二醇干扰素（PEG-IFNα-2a或IFNα-2b）治疗52周,随访24周,其中146例（A组）初始24周联合核苷（酸）类似物治疗（59例联合拉米夫定,56例联合阿德福韦酯,31例联合恩替卡韦）,另61例单用IFN治疗（B组）。结果 A、B组治疗结束时HBV DNA阴转率分别为86.3%（126/146）、65.6%（40/61）;ALT复常率87.7%（128/146）、76.5%（39/61）;HBeAg阴转率分别为69.3%（70/101）、40%（10/25）;HBsAg阴转率分别为30.1%（44/146）、16.4%（10/61）;抗-HBs阳转率分别为26.7%（39/146）、11.5%（7/61）,差异均有统计学意义（P〈0.05）。结论 IFN联合核苷（酸）类似物治疗慢性乙型肝炎的疗效优于单用IFN组。     

干扰素联合胸腺肽治疗慢性乙型肝炎临床疗效观察

慢性乙型病毒肝炎是我国的常见病、多发病,是引起肝硬化、肝癌的最主要原因。1资料与方法1·1一般资料本组66例系本院2000年~2003年的住院患者,ALT均异常,HBsAg( )、HBeAg( )、抗-HBc( )。治疗组36例,男26例,女10例,平均24岁;对照组30例,男性21例,女性9例平均年龄34岁,两组的年     

核苷类药物治疗慢性乙型肝炎的新进展

据WHO统计,全球有近20亿人被乙型肝炎病毒(HBV)感染,其中约有3.5亿人为HBV慢性感染者,中国占1/3。每年约有120万HBV感染患者死于HBV相关疾病,所以寻找有效的治疗乙型肝炎药物成为当务之急。慢性乙型肝炎的关键治疗是抗HBV治疗,核苷类药物可以直接抑制HBV复制,它包括嘧啶类的拉米夫定、恩曲他滨、克拉夫定,以及嘌呤类的阿德福韦酯、恩替卡韦等。目前核苷类药物发展迅速,为此就目前进入临床和正在研发的部分核苷类药物的研究进展作一综述。1嘧啶类核苷类似物1.1拉米夫定(lamivudine,LAM)拉米夫定是目前应用范围最广的核苷类抗HBV药…     

聚乙二醇干扰素α-2a联合核苷(酸)类似物治疗慢性乙型肝炎研讨会纪要

2010年9月,<中华传染病杂志>、<中华肝脏病杂志>、<中国病毒病杂志>联合组织召开了"聚乙二醇干扰素α-2a联合核苷(酸)类似物治疗慢性乙型肝炎研讨会".根据目前国内外聚乙二醇干扰素α-2a联合治疗的研究结果,与会专家对联合治疗的目标、策略等进行了认真讨论,并形成<聚乙二醇干扰素α-2a联合核苷(酸)类似物治疗慢性乙型肝炎研讨会纪要>,供读者参考,并将在今后的实践中不断完善和更新.     

干扰素在治疗慢性乙型肝炎中的应用

干扰素的发现及应用是抗病毒治疗的一个里程碑，“迄今为止，没有任何一项科学发现象干扰素这样对病毒性肝炎的治疗产生如此重大的影响”（引自2007年美国肝病年会宣传手册）。干扰素作用广泛，具有其抗病毒、抗增殖、抗肘瘤以及免疫调节活性。根据其受体不同可将干扰素分为I型（α和β）和Ⅱ型（γ），用于治疗慢性乙型肝炎的主要是干扰素α。1995年聚乙二醇化干扰素（PEG-IFN）研制威功，其优越的药代动力学和药效学特性给慢性乙型肝炎的治疗带来重大进展。[第一段]     

聚乙二醇干扰素α治疗HBeAg阴性慢性乙型肝炎的应答指导治疗策略及停药时机

我国HBeAg阴性慢性乙型肝炎(CHB)占CHB患者的30％ ～ 40％,且有增长趋势[1];以基因B、C型为主.HBeAg阴性CHB患者ALT持续或反复异常,肝组织学检查肝脏病变较重,病情缓解比例低,发生肝硬化、临床失代偿和肝细胞肝癌(HCC)概率高;对当前治疗的应答率低、复发率高.     

聚乙二醇干扰素初始联合核苷(酸)类似物治疗慢性乙型肝炎的疗效观察

[目的]观察聚乙二醇干扰素初始联合核苷(酸)类似物治疗e抗原阳性慢性乙型肝炎(CHB)患者的疗效。[方法]对60例慢乙肝治疗患者进行研究,A组患者(n=29)使用聚乙二醇干扰素α-2a(Peg-IFNα-2a)联合阿德福韦酯治疗48周,B组患者(n=31)使用Peg-IFNα-2a联合阿德福韦酯及拉米夫定治疗48周。观察治疗过程中12、24、48周时患者ALT复常率、HBV-DNA应答率、HBeAg、HBsAg的转阴率和转换率。[结果]2组治疗结束时ALT复常率分别为82.8%(24/29)、83.9%(26/31),HBV-DNA应答率分别为86.2%(25/29)、90.3%(28/31),HBeAg血清学转换率分别为34.5%(10/29)、35.5%(11/31),HBsAg血清学转换率6.9%(2/29)、6.5%(2/31),差异无统计学意义(P0.05)。[结论]Peg-IFNα-2a联合阿德福韦酯及拉米夫定治疗慢乙肝未显示疗效优势,初始全程Peg-IFNα-2a联合阿德福韦酯抗病毒治疗,可以提高病毒抑制的速度和血清学转换率。     

核苷(酸)类似物联合干扰素治疗HBeAg阳性慢性乙型肝炎120周的疗效随访

目的 观察核苷(酸)类似物联合干扰素延长疗程至96周治疗HBeAg阳性慢性乙型肝炎,随访24周的疗效. 方法 135例HBeAg阳性慢性乙型肝炎患者,90例接受核苷(酸)类似物联合干扰素治疗(联合治疗组),45例接受单一核苷(酸)类似物治疗(对照组).分别在治疗12、24、48、72、96周及随访24周时进行生物化学、病毒学、血清学评估.应答疗效比较采用x2检验. 结果 135例患者纳入分析.联合治疗组90例完成96周疗程后,17例(占18.9％)患者发生HBsAg血清学转换,37例(占41.1％)患者发生HBeAg血清学转换;对照组无患者发生HBsAg血清学转换,15例(占33.3％)患者发生HBeAg血清学转换,联合治疗组HBsAg血清学转换明显高于对照组,x2=8.08,P＜ 0.01,差异有统计学意义.两组患者HBeAg血清学转换差异无统计学意义.出现HBsAg血清转换＜ 30岁为64.7％ (11/17),30 ～ 40岁为9.7％(6/62),＞40岁11例中无一例出现HBsAg血清转换,＜ 30岁患者HBsAg血清转换率明显高于其他年龄组,x2值分别是12.62和4.24,P值均＜0.05,差异有统计学意义. 结论 核苷(酸)类似物联合干扰素延长疗程治疗HBeAg阳性慢性乙型肝炎能提高HBsAg血清学转换,年龄＜30岁者出现HBsAg血清学转换比例最高.     

干扰素治疗慢性乙型肝炎的疗效预测及影响因素

IFNα是目前国际公认的治疗CHB的有效药物之一。CHB患者在IFNα治疗6～12个月后,ALT复常率为34%～45%,HBeAg消失和(或)抗-HBe出现率为15%～37%,HBV DNA阴转率(<105拷贝/ml)为37%,HBsAg阴转率为1%～8%。导致CHB患者在IFN治疗后取得持续性应答、部分应答或者无应答的原因是临床和基础研究非常关心的问题,现就IFN疗效的预测和影响因素作简要综述。     

干扰素联用苦参素治疗慢性乙型肝炎的疗效观察

目的观察干扰素联用苦参素治疗慢性乙型肝炎的疗效。方法设置观察组和对照组，观察组用塞诺金（a2b干扰素）和博尔泰力联用，对照组单用干扰素。结果治疗6个月和1年后复查，观察组HBV-DNA及HBeAg阴转率均明显高于对照组（P〈0．01）。结论提示干扰素联用苦参素治疗慢性乙型肝炎有协同作用，值得在临床推广使用。     

Lamivudine and alpha interferon combination treatment of patients with chronic hepatitis B infection: a randomised trial

BACKGROUND, AIM, AND METHODS: Alpha interferon is the generally approved therapy for HBe antigen positive patients with chronic hepatitis B, but its efficacy is limited. Lamivudine is a new oral nucleoside analogue which potently inhibits hepatitis B virus (HBV) DNA replication. To investigate the possibility of an additive effect of interferon-lamivudine combination therapy compared with interferon or lamivudine monotherapy, we conducted a randomised controlled trial in 230 predominantly Caucasian patients with hepatitis B e antigen (HBeAg) and HBV DNA positive chronic hepatitis B. Previously untreated patients were randomised to receive: combination therapy of lamivudine 100 mg daily with alpha interferon 10 million units three times weekly for 16 weeks after pretreatment with lamivudine for eight weeks (n=75); alpha interferon 10 million units three times weekly for 16 weeks (n=69); or lamivudine 100 mg daily for 52 weeks (n=82). The primary efficacy end point was the HBeAg seroconversion rate at week 52 (loss of HBeAg, development of antibodies to HBeAg and undetectable HBV DNA). RESULTS: The HBeAg seroconversion rate at week 52 was 29% for the combination therapy, 19% for interferon monotherapy, and 18% for lamivudine monotherapy (p=0.12 and p=0.10, respectively, for comparison of the combination therapy with interferon or lamivudine monotherapy). The HBeAg seroconversion rates at week 52 for the combination therapy and lamivudine monotherapy were significantly different in the per protocol analysis (36% (20/56) v 19% (13/70), respectively; p=0.02). The effect of combining lamivudine and interferon appeared to be most useful in patients with moderately elevated alanine aminotransferase levels at baseline. Adverse events with the combination therapy were similar to interferon monotherapy; patients receiving lamivudine monotherapy had significantly fewer adverse events. CONCLUSIONS: HBeAg seroconversion rates at one year were similar for lamivudine monotherapy (52 weeks) and standard alpha interferon therapy (16 weeks). The combination of lamivudine and interferon appeared to increase the HBeAg seroconversion rate, particularly in patients with moderately elevated baseline aminotransferase levels. The potential benefit of combining lamivudine and interferon should be investigated further in studies with different regimens of combination therapy.     

多次抗病毒治疗无效的慢性乙型肝炎患者停用抗病毒药物后的联合治疗

目的 对于干扰素治疗无效、核苷类似物耐药后停用抗病毒药物治疗的慢性乙型肝炎患者,探讨其停药的后果及再联合应用核苷类似物长期治疗的必要性.方法 先后用干扰素α-2b、核苷类似物抗病毒治疗均无效的42例慢性乙型肝炎患者,其自动停用抗病毒药物一段时间后,再联用拉米夫定(100 mg/d)(或替比夫定600 mg/d、恩替卡韦...     

拉米夫定联合干扰素α治疗慢性乙型肝炎疗效观察

目的研究拉米夫定联合干扰素α对慢性乙型肝炎病人的疗效。方法对1999~2001年深圳市东湖医院慢性乙型肝炎病人87例,随机分为2组,观察组36例,用拉米夫定(100mg/d)联合干扰素α(每次5mU)隔日1次肌注,26周后单用拉米夫啶至104周。对照组51例,单用拉米夫啶100mg/d,疗程104周,并评估疗效。结果两组HBVDNA转阴率差异无显著性(P=0.24),联合治疗组的HBeAg/抗-HBe血清转换率高于拉米夫定组(38.9%对17.6%,P=0.03)。联合治疗组的HBVYMDD变异率较低(22.2%对43.1%,P=0.04)。结论联合治疗的2年疗效优于单用拉米夫定,且能减少病毒YMDD变异。     

六味五灵片联合替比夫定治疗慢性乙型肝炎肝纤维化疗效分析

目的：观察六味五灵片联合替比夫定（ LdT）治疗慢性乙型肝炎（ CHB）肝纤维化的临床疗效。方法：将120例CHB肝纤维化患者随机分为观察组和对照组。观察组（64例）患者口服六味五灵片和LdT,对照组（56例）患者单用LdT,疗程均为24周。比较两组患者治疗前后的临床症状、肝功能及肝纤维化指标变化情况。结果：治疗24周后,观察组患者ALT、 AST、 TBil分别为（25.4±16.3） U/L、（28.4±15.9） U/L、（22.8±10.7）μmol/L,均明显低于对照组（44.7±19.6） U/L、（40.1±17.1） U/L、（35.2±11.5）μmol/L ,差异有显著性意义（ P＜0.05）。治疗后两组患者肝纤维化指标均显著下降,且观察组下降幅度优于对照组（P＜0.05）。结论：六味五灵片联合LdT能够明显改善CHB肝纤维化患者的肝功能,促进HBV DNA转阴,同时还能显著降低患者的血清肝纤维化指标,提高临床疗效。     

慢性乙型肝炎联合抗病毒治疗研究进展

抗病毒治疗是慢性乙型肝炎治疗的重要手段。目前单一药物的疗效不令人满意,越来越多的研究数据表明药物联合抗病毒治疗,包括干扰素α和核苷（酸）类似物联合治疗以及两种核苷（酸）类似物联合治疗可以减少耐药发生、提高抗病毒疗效,因而联合抗病毒治疗可能是控制乙肝的有效策略。     

Virological efficacy of combination therapy with corticosteroid and nucleoside analogue for severe acute exacerbation of chronic hepatitis B

The short‐term prognosis of patients with severe acute exacerbation of chronic hepatitis B (CHB) leading to acute liver failure is extremely poor. We have reported the efficacy of corticosteroid in combination with nucleoside analogue in the early stages, but virological efficacy has not been documented. Our aim was to elucidate the virological efficacy of this approach. Thirteen patients defined as severe acute exacerbation of CHB by our uniform criteria were prospectively examined for virological responses to treatment. Nucleoside analogue and sufficient dose of corticosteroids were introduced as soon as possible after the diagnosis of severe disease. Of the 13 patients, 7 (54%) survived, 5 (38%) died and 1 (8%) received liver transplantation. The decline of HBV DNA was significant between the first 2 weeks (P = 0.02) and 4 weeks (P < 0.01). Mean reduction in HBV DNA during the first 2 weeks was 1.7 ± 0.9 log copies per mL in overall patients, 2.1 ± 0.8 in survived patients and 1.2 ± 0.9 in dead/transplanted patients. The decline of HBV DNA was significant between the first 2 weeks (P = 0.03) and 4 weeks (P = 0.02) in survived patients, but not in dead/transplanted patients. Our study shows that corticosteroid treatment in combination with nucleotide analogue has sufficient virological effect against severe acute exacerbation of CHB, and a rapid decline of HBV DNA is conspicuous in survived patients.     

Effect of nucleoside analog‐interferon sequential therapy on patients with acute exacerbation of chronic hepatitis B

Aim: Nucleoside analog (NA)‐interferon (IFN) sequential therapy may enable the long‐term control of chronic hepatitis B (CHB) and the withdrawal of the nucleoside analog. We evaluated the efficacy of NA‐IFN sequential therapy for acute exacerbation of CHB. Methods: A total of 12 patients with acute exacerbation of CHB, nine of whom were positive for hepatitis B e antigen (HBeAg), were enrolled in this study. All the patients were treated with lamivudine 100 mg/day alone for 20 weeks, then with both IFN‐α 6 megaunits three times per week and lamivudine for 4 weeks, and lastly, with IFN‐α alone for 20 weeks. Patients whose serum alanine aminotransferase (ALT) level was normalized, whose serum hepatitis B virus (HBV) DNA level decreased to less than 5 log copies/mL, and HBeAg level was absent 24 weeks after the end of treatment were defined as having sustained virological response (SVR). The other patients were defined as having no response (NR). Results: Four out of nine (44.4%) HBeAg‐positive and all three HBeAg‐negative patients achieved SVR. The levels of serum alanine aminotransferase (ALT), HBV DNA and HBV core‐related antigen were similar between SVR and NR patients at baseline. Three of four patients (75.0%) whose serum HBeAg became negative at the end of treatment achieved SVR, while one of five (20.0%) whose serum HBeAg remained positive achieved SVR. Conclusion: NA‐IFN sequential therapy for patients with acute exacerbation of CHB enables the withdrawal of treatment and is particularly effective for patients whose serum HBeAg has become undetectable by the end of the IFN treatment.     

Sequential combination therapy of HBe antigen-negative/virus-DNA-positive chronic hepatitis B with famciclovir or lamivudine and interferon-alpha-2a.

BACKGROUND/AIMS: Hepatitis B e antigen-negative/hepatitis B virus (HBV) DNA-positive chronic hepatitis B (CHBe-) exhibits a high relapse rate on monotherapy with lamivudine or interferon-alpha (IFN-alpha). We investigated, whether sequential therapy with famciclovir or lamivudine followed by combination with IFN-alpha-2a improves durable virologic response in CHBe- characterized by mutation analysis of the HBV precore genome region. METHODS: Fourteen patients were treated with famciclovir (n=3) or lamivudine for 4 weeks to reduce the viral load, and subsequently with the combination of the nucleoside analogue and IFN-alpha-2a until 16 weeks beyond the loss of serum HBV-DNA. RESULTS: Median duration of therapy was 29.0 weeks (range 20.6-48.3 weeks). Serum HBV-DNA was undetectable and alanine aminotransferase had normalized in all patients at the end of treatment. Seven (50%) patients maintained a sustained response 12 months after end of treatment. Only two of them had been infected by HBV with the G1896A mutation. Most patients (5/7) with the G1896A mutation relapsed within 4 months after therapy. CONCLUSION: Sequential combination therapy can induce sustained virologic response in a subgroup of CHBe-, but most with the G1896A precore mutant HBV relapse. Trials of CHBe- should be based on characterization of HBV mutants.