干扰素联合利巴韦林治疗不同病毒基因型慢性丙型肝炎患者的疗效

目的 观察干扰素联合利巴韦林治疗不同病毒基因型慢性丙型肝炎的疗效.方法 选择120例慢性丙型肝炎患者,采用特异性探针杂交法进行丙型肝炎病毒基因分型,根据基因分型结果将患者分为丙型肝炎病毒1b型感染的长效干扰素组(皮下注射聚乙二醇干扰素α-2a,180 μg/次,1次/周)和非1b型感染的普通干扰素组(皮下注射普通干扰素α-2b,5 mIU/次,隔日1次),2组患者均口服利巴韦林.治疗前后和随访中检测患者血浆丙型肝炎病毒RNA和ALT水平作为疗效评价的指标.比较治疗结束后2组患者肝功能异常率的差异.结果 长效干扰素组与普通干扰素组获得持续病毒学应答者分别为30例(46.2％)和41例(74.5％),组间比较差异有统计学意义(P＜0.05).长效干扰素组肝功能异常者10例(15.4％),普通干扰素组有8例(14.5％),2组患者肝功能异常率比较差异无统计学意义(x2=0.01,P＞0.05).结论 聚乙二醇干扰素α-2a联合利巴韦林治疗丙型肝炎病毒1b型感染患者的疗效不理想,丙型肝炎病毒基因型主要影响治疗的难易程度.     

干扰素α个体化治疗HBeAg阳性慢性乙型肝炎患者的疗效观察

目的观察干扰素α(IFNα)个体化治疗HBeAg阳性慢性乙型肝炎患者的临床应答和远期疗效。方法对53例HBeAg阳性慢性乙型肝炎患者,治疗前行肝穿刺病理检查确诊,给予注射用重组人IFNα-1b,50μg、隔日1次、皮下注射。每隔3个月检测血清HBV DNA定量和HBeAg、HBsAg,定量降低者进行延长治疗。治疗结束后于3个月、6个月、1年、3年、5年、7年进行随访。结果 53例HBeAg阳性慢性乙型肝炎接受不同疗程(24～100周)的IFNα-1b,治疗结束时,近期应答者34例,应答率64.15%,疗程48～100周。其中完全应答者24例(45.28%),部分应答者10例(18.87%),无应答者19例(35.85%)。三组患者之间年龄和IFNα疗程的差异有统计学意义(P=0.011,P=0.000)。完全应答者中2例患者在疗程68、80周结束时HBsAg阴转(3.77%)。随访期间完全应答组1年内复发1例。部分应答组复发8例:分别在6个月、1年和3年复发3例、4例、1例。结论 IFNα个体化治疗HBeAg阳性慢性乙型肝炎患者,疗程长、年龄小者近期应答率高,完全应答者远期复发率低。     

Hepatitis C virus-specific cytotoxic T cell response restoration after treatment-induced hepatitis C virus control

Hepatitis C virus(HCV)-specific cytotoxic T cell(CTL) response plays a major role in viral control during spontaneous infection resolution. These cells develop an exhausted and pro-apoptotic status during chronic onset, being unable to get rid of HCV. The role of this response in contributing to sustained viral response(SVR) after anti-HCV is controversial. Recent studies show that after successful interferon-based anti-HCV treatment, HCV traces are still detectable and this correlates with a peak of HCV-specific CTL response activation, probably responsible for maintaining SVR by subsequent complete HCV clearing. Moreover, SVR patients’ serum is still able to induce HCV infection in na?ve chimpanzees, suggesting that the infection could be under the control of the immune system after a successful treatment, being transmissible in absence of this adaptive response. At least theoretically, treatmentinduced viral load decrease could allow an effective HCV-specific CTL response reestablishment. This effect has been recently described with anti-HCV interferonfree regimes, based on direct-acting antivirals. Nevertheless, this is to some extent controversial with interferon-based therapies, due to the detrimental immunoregulatory α-interferon effect on T cells. Moreover, HCV-specific CTL response features during anti-HCV treatment could be a predictive factor of SVR that could have clinical implications in patient management. In this review, the recent knowledge about the role of HCV-specific CTL response in the development of SVR after anti-HCV treatment is discussed.     

细胞毒性T淋巴细胞对慢性乙型肝炎干扰素α抗病毒疗效的预测

目的 研究细胞毒性T淋巴细胞(CTL)是否可以作为慢性乙型肝炎干扰素抗病毒疗效的预测因素.方法 以穿孔素阳性淋巴细胞标记细胞毒性T细胞;分析125例注射干扰素治疗患者持续应答组及无应答组干扰素治疗前血清转氨酶、肝组织炎症分级、HBVDNA载量、肝组织纤维化程度分级,肝组织穿孔素阳性淋巴细胞数与干扰素疗效的相关性.结果 仅血清HBVDNA＜ 106拷贝/ml时,持续应答组及无应答组肝组织穿孔素阳性淋巴细胞数差异有统计学意义(P＜0.05).结论 血清HBVDNA＜ 106拷贝/ml时,肝组织穿孔素阳性淋巴细胞数可以作为慢性乙型肝炎干扰素抗病毒疗效预测因素.     

α干扰素治疗HBeAg阳性慢性乙型肝炎疗效的荟萃分析

目的评价α干扰素治疗HBeAg阳性慢性乙肝病毒感染儿童的长期疗效及安全性。方法检索PubMed和CHKD期刊全文数据库,并追查所有纳入研究的参考文献,进行荟萃分析。纳入用英文或中文发表的比较α干扰素与非抗病毒药物（安慰剂或空白对照）治疗HBeAg阳性慢性乙肝病毒感染儿童的随机对照试验。结果共纳入10个随机对照试验,包括542个HBsAg和HBeAg阳性的慢性乙型肝炎患儿。结果显示,随访6个月～2年,α干扰素组HBeAg转阴率高于对照组[31．1％vs12．4％,OR3．17,95％CI（2．00,5．02）,P〈0．00001],HBV—DNA转阴率高于对照组[33．9％vs16．2％,OR2．59,95％CI（1．70,3．96）,P〈0．0001],HBsAg转阴率高于对照组[5．5％vs1．2％,OR3．44,95％CI（1．20,9．89）,P=0．02],丙氨酸氢基转移酶（ALT）复常率高于对照组[43．0％vs27．7％,OR1．99,95％CI（1．16,3．42）,P=0．01],HBeAg血清学转换率高于对照组[30．4％vs12．8％,OR2．90,95％CI（1．56,5．39）,P=0．0008],两组差异均有统计学意义,但HBsAg血清学转换率与对照组相比[1．9％vs0,95％CI（0．42,18．13）,P=0．29],差异无统计学意义。结论对HBeAg阳性的慢性乙肝病毒感染患儿,α干扰素可能有使HBeAg转阴、HBV-DNA转阴、HBsAg转阴、ALT复常及HBeAg血清学转换的效应,但未能实现HBsAg血清学转换。受原研究质量和不同研究干预措施差异的影响,α干扰素的效应尚需更多高质量足够样本量的随机对照试验予以证实。     

博尔泰力（苦参素）治疗慢性乙型肝炎临床疗效观察

目的：探讨博尔泰力治疗慢性乙肝的合理剂量及远期疗效。方法：博尔泰力注射液I组（400mg)治疗慢性乙肝74例,Ⅱ组（600mg)治疗慢性乙肝90例,与α－干扰素（IFN－α）治疗的慢性乙肝75例比较并随访1年。结果：博尔泰力I组HBeAg阴转率32．4％,HBV－DNA阴转率37．8％;II组分别为36．7％和40．0％;IFN－α组分别为41．3％和44．0％（P＞0．05）。1年后随访博尔泰力I组二项阴转率分别为36．1％和27．9％;II组二项阴转率分别为38．5％和29．5％;IFN－α组二项阴转率分别为42．4％和42．4％（P＞0．05）,结论：博尔泰力注射液治疗Ⅰ,Ⅱ组对慢 性乙肝远期疗效均良好,可与干扰素媲美,有望成为治疗慢性乙肝的有效药物。     

IFN-α抑制HUVECs以及荷人肝癌裸小鼠血管生成的实验研究

目的: 检测IFN-α体内外对人脐静脉血管内皮细胞（HUVECs）的抑制作用，探讨IFN-α抑制肝癌血管生成的机制。方法： 运用细胞增殖抑制试验、MTT试验、管样结构形成试验、移动抑制试验以及裸鼠体内移植瘤生长和血管密度测定探讨IFN-α对HUVECs的抑制作用。结果： IFN-α对HUVECs的细胞增殖、移动和管样结构形成试验有明显的抑制作用，体内实验提示试验组移植瘤直径明显小于对照组，微血管密度（MVD）亦明显低于对照组。结论： IFN-α可以通过抑制肿瘤的血管新生，起到抑制肿瘤生长的作用。     

Systemic lupus erythematosus arising during interferon-alpha therapy for cryoglobulinemic vasculitis associated with hepatitis C

We present the case of a 53-year-old woman who developed systemic lupus erythematosus (SLE) after being treated with interferon-alpha (IFN-) for cryoglobulinemic vasculitis associated with hepatitis C virus (HCV) infection. Her cryoglobulinemic vasculitis resolved rapidly with IFN- treatment. However, after 10 months of IFN- therapy, she developed a photosensitive malar rash, oral ulcers, arthralgias, lymphopenia, and anti-SSA autoantibodies. She was diagnosed with SLE induced by IFN- therapy. IFN- was discontinued, she was treated with a short course of prednisone and hydroxychloroquine, and she improved rapidly. This is the first report of IFN--induced SLE complicating treatment of cryoglobulinemic vasculitis associated with HCV infection. The development of SLE during therapy with IFN- could be due to direct immunomodulation by IFN-, and review of experimental data and prior case reports suggests a pathogenic role for IFN- in SLE.No financial support or conflict of interest to declare     

The activation of intracellular tyrosine kinases by interferon-alpha (IFNα) correlates with its antiproliferative activity in B-lymphoid cell lines, but not in B-cell chronic lymphocytic leukemia patients

 The response to interferon-alpha (IFNα) treatment in leukemias of the B-cell lineage shows a marked heterogeneity. A distinct subset of patients with B-CLL responds to treatment with IFNα, while the drug has no therapeutic effect in the majority of patients. The mechanism of this phenomenon is poorly understood. The cellular events induced by this cytokine mediated by a number of specific signaling events. Therefore, we studied the effect of recombinant IFNα on tyrosine phosphorylation and proliferation of cytosolic proteins in human cell lines and in freshly isolated B-CLL cells in order to test the potential value of these events as a pretreatment test for IFNα in CLL. In human lymphoid cell lines, IFNα induced tyrosine phosphorylation of multiple cytosolic proteins in a time- and concentration-dependent manner. This effect correlated with its growth-inhibitory effect in almost all cell lines. In marked contrast, in freshly isolated B-CLL cells IFNα seemed to have both stimulatory and inhibitory effects on proliferation, but it consistently stimulated tyrosine phosphorylation. Moreover, the clinical response of B-CLL to IFNα did not correlate with the activation of tyrosine kinases nor with the inhibition of cell growth in vitro. Therefore, the assessment of IFNα-induced tyrosine phosphorylation of cytosolic phosphoproteins does not allow to predict the treatment response to IFNα in CLL patients. Received: March 24, 1999 / Accepted: July 19, 1999