Interferon therapy for chronic hepatitis B

This article summarizes the results obtained with interferon alfa and pegylated interferon alfa, as monotherapy and in combination with lamivudine, in the treatment of chronic hepatitis B.     

慢性乙型肝炎的干扰素治疗

慢性乙型肝炎已成为全球一个严重的健康问题.HBV慢性感染者可发展为肝硬化、失代偿肝病以及肝细胞肝癌.抗病毒治疗是慢性乙型肝炎最关键的治疗方法,持续抑制或清除HBV可改善肝脏炎症及纤维化,降低HBV相关并发症.目前公认有效的抗HBV药物主要包括干扰素和核苷酸类似物.     

Interferon combination therapy for HIV/hepatitis C virus coinfection

IFN-α has been the cornerstone of chronic hepatitis C virus (HCV) treatment for over a decade. Yet, rates of sustained virologic response of HCV infection to interferon-based therapy, particularly in difficult-to-treat populations, have been disappointingly low. This is particularly true in HIV/HCV coinfection, in which less than a third of patients typically respond to therapy. New HCV protease inhibitors, most of which will need to be administered with pegylated interferon, are in development, but comprehensive, long-term data for their use in coinfected patients is not yet available. Understanding the basis of this population's poor response to interferon-based therapy is crucial to future exploration of new therapeutic options, immunotherapy and prognosis in HIV/HCV-coinfected population.     

Interferon/long-term lamivudine combination therapy in anti-HBe positive chronic hepatitis B patients

BACKGROUND: Monotherapy with a single antiviral agent is insufficient in controlling hepatitis B virus infection in the majority of patients with anti-HBe positive chronic hepatitis B. Interferon/long-term lamivudine combination therapy was evaluated to determine if this strategy would improve treatment efficacy and reduce the emergence of lamivudine resistance. METHODS: In total, 36 consecutive anti-HBe positive patients were treated with interferon (3 MU subcutaneously three times weekly) and lamivudine (100 mg orally once a day) for 12 months. After completion of the combined treatment, all patients continued to receive lamivudine monotherapy indefinitely. RESULTS: Overall, 35 patients (97%) showed virological response at 12 months. Four patients (11%) cleared HBsAg and developed anti-HBs. During the follow-up time, after the discontinuation of interferon, of 30 +/- 12 months (range: 7-57 months), 13 patients (36%) exhibited breakthrough infection. The cumulative rates of breakthrough infection at the end of 1, 2, 3 and 4 years of treatment were 0%, 14%, 32%, and 59%, respectively. CONCLUSIONS: Combination therapy appears to be effective and may also delay the selection of lamivudine-resistant variants. However, controlled trials are definitely warranted to clarify the potential benefits of combination antiviral treatment over monotherapy.     

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。     

Interferon and lamivudine combination therapy versus lamivudine monotherapy for hepatitis B e antigen-negative hepatitis B treatment: a meta-analysis of randomized controlled trials

BACKGROUND:It has been demonstrated that only a minority of patients with hepatitis B e antigen(HBeAg)-negative chronic hepatitis B(CHB) obtain a sustained response after either interferon(IFN) or nucleos(t)ide analogue monotherapy.Therefore,combination therapy of drugs with synergistic antiviral effects was proposed to have a sustained response in these patients.We compared the effect and safety of lamivudine monotherapy and its combination with IFN including conventional interferon(CON-IFN) and pegylated interferon(PEG-IFN) for HBeAg-negative CHB patients.DATA SOURCES:A group of three independent reviewers identified 9 eligible randomized controlled trials through electronic searches(MEDLINE,OVID,EMBASE,the Cochrane Library Clinical Trials Registry,and the Chinese Medical Database),manual searches,and contact with experts.Sustained virological and biochemical responses were defined as primary efficacy measures.We performed quantitative meta-analyses to assess differences between CON-IFN plus lamivudine combination and lamivudine monotherapy groups.RESULTS:No greater sustained virological and biochemical rates were found in patients receiving CON-IFN/lamivudine combination therapy [29.1% vs.26.7%,odds ratio(OR)=0.98,95% confidence interval(CI) 0.65-1.50,P=0.94,and 41.8% vs.40.3%,OR=1.13,95% CI 0.78-1.65,P=0.51,respectively],though a reduced YMDD mutation rate was achieved in the combination group [8.39% vs.30.0%,OR=0.16,95% CI 0.076-0.33,P0.001].However,data from one PEG-IFN trial showed greater sustained virological and biochemical rates in patients receiving combination therapy [response rate 19.5% vs.6.6%,OR=3.42,95% CI 1.71-6.84,P0.001 and 60.0% vs.44.2%,OR=1.88,95% CI 1.23-2.85,P=0.003,respectively].CONCLUSIONS:Addition of CON-IFN to lamivudine did not improve treatment efficacy but suppressed YMDD mutation by lamivudine.Combination of PEG-IFN and lamivudine might increase the sustained response,and further clinical trials are needed for confirmation.     

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.     

双环醇在慢性乙型肝炎联合治疗中的应用

目前普遍认为,HBV病毒水平是慢性乙型肝炎病程转归的决定因素,因此抗病毒治疗正成为慢性乙型肝炎治疗的主流趋势;同时,病理生理机制研究目前还不能完全清楚地揭示肝脏炎症触发后的确切变化过程,传统的非特异性抗炎治疗逐渐被边缘化。干扰素和核苷（酸）类似物的应用使得血清病毒标志物和HBVDNA水平有了改善,但在慢性乙型肝炎的治疗方面,仍然存在缺憾：现有抗病毒药物,无论干扰素类或核苷（酸）类似物类,对HBV的控制均不能达到令人满意的效果;     

Interferon therapy for chronic hepatitis C

Interferon alone is currently the treatment of choice for chronic hepatitis C. The optimal treatment regimen continues to be defined and refined by clinical studies. The variability of the response to interferon seems to be influenced by several factors, including liver histology, viral genotype, level of viraemia, number of predominant quasispecies, and perhaps the type of interferon and treatment regimen. It is therefore quite likely that, in the future, treatment regimens will be tailored to the individual patient in order to maximize the likelihood of a beneficial outcome. It is also likely that the increasing availability of sensitive, quantitative, and affordable assays of hepatitis C viral levels will allow physicians to assess treatment response quite differently from the way we do so today. This will change our philosophy such that we will begin to view and treat chronic hepatitis C as an infection, instead of simply as a liver disease.     

拉米夫定联合胸腺肽加乙肝疫苗治疗慢性乙型肝炎的临床观察

目的观察拉米夫定联合胸腺肽加乙肝疫苗治疗慢性乙型肝炎的临床效果。方法100例未曾接受过抗病毒治疗的慢性乙型肝炎患者随机分为治疗组和对照组,治疗组50例,给予拉米夫定100mg,每日一次口服,同时乙肝疫苗10μg皮下注射,每两周一次,胸腺肽20mg肌肉注射,隔日一次,共计26周,随后继续使用拉米夫定和乙肝疫苗26周,总疗程52周;对照组给予拉米夫定100mg·d-1,疗程52周。结果治疗结束时治疗组ALT下降、HBeAg/抗-HBe血清转换率明显高于对照组,差异有显著性(P<0·01),但HBVDNA下降差异无显著性(P<0·01),停药后随访6月、12月,治疗组ALT及HBVDNA下降、HBeAg/抗-HBe血清转换率明显高于对照组比,差异有显著性(P<0·01)。治疗组的完全应答率与对照组比,差异有高度显著性(P<0·01)。结论拉米夫定联合胸腺肽加乙肝疫苗能明显提高临床疗效及HBeAg/抗-HBe血清转换率及HBVDNA阴转率,且无明显毒性反应。     

核苷的亲脂性磷酸酰胺酯β-LPA体外抗乙型肝炎病毒的作用

目的:探讨β-LPA体外抗乙型肝炎病毒(hepatitis B virus,HBV)的作用. 方法:通过β-LPA干预培养HepG2.2.2.15细胞,ELISA法检测上清HBsAg和HBeAg,32p标记HBV DNA为探针,Southern blot法检测细 胞内的HBV DNA,再以计算机图像处理进行定量分析,得出50%抑制的药物浓度(ED50),以MTT法检测不同浓度药物的细胞毒性,求出50%细胞抑制的药物浓度(ID50).结果:β-LPA体外明显抑制HBV DNA的复制,并呈浓度依赖性.ED50为0.01 μmol/L,β-LPA 细胞毒性实验显示ID50为50 μmol/L.低浓度的β-LPA对上清HBsAg,HBeAg无明显影响,高浓度时有显著的抑制作用.结论:β-LPA具有明显的体外抑制病毒DNA复制作用,且细胞毒性小.