慢性丙型肝炎患者抗干扰素中和抗体检测及其意义

４０例慢性丙型肝炎分为两组接受重组α干扰素治疗。用细胞变抑制法测定治疗前、治疗中和治疗后病人血清抗干扰素中和抗体。结果显示，接受干扰素αｌ治疗的病人中和抗体产生率为７．７％，显著高于干扰素α－２ｂ治疗的病人。     

聚乙二醇干扰素治疗慢性丙型肝炎疗效及其影响因素

丙型肝炎病毒(HCV)是引起输血后肝炎和散发性非甲非乙型肝炎的主要病原，其中20％～30％的患者可进展为肝硬化甚至肝癌，对人类危害极大。10多年来，干扰素α曾被选择性地用于治疗慢性丙型肝炎(简称慢丙肝)，它对于改善患者肝功能、预防肝纤维化乃至HCV相关的肝癌具有重要意义，然而只有10％～15％的患者1能治疗成功。近年，聚乙二醇干扰素(PEG-IFN)已被用于慢性肝病和肝硬化治疗的临床研究，     

干扰素中和抗体对干扰素治疗慢性乙型肝炎效果的影响

在慢性病毒性肝炎治疗中,正广泛应用干扰素,并取得了较好的疗效,但仍有相当部分患者无应答,影响干扰素抗病毒疗效的因素很多,干扰素抗体的作用也是因素之一.在干扰素治疗慢性病毒性肝炎的过程中,干扰素能刺激机体产生干扰素中和抗体,为了探讨中和抗体的产生率及其临床意义,我们采用中和生物法检测了接受干扰素治疗的慢性乙型肝炎患者血清干扰素中和抗体,探讨了干扰素中和抗体对干扰素疗效的影响.     

聚乙二醇化干扰素α-2α治疗慢性丙型肝炎的疗效与安全性

聚乙二醇化干扰素α-2α(PEG—IFNα-2α，派罗欣，罗氏)，改变了干扰素(IFN)的药代动力学。其血清半衰期增加了大约10倍，同时增加了药物的药理学活性。一次注射可维持有效的抑制病毒的血药浓度长达7d，从而提高临床疗效。国外多项临床对照研究已经证实，PEG—IFNα-2α治疗慢性丙型肝炎的疗效明显优于IFNα-2α，能显著提高患者的持续病毒学应答。     

老年慢性丙型肝炎患者抗病毒治疗的疗效及安全性

目的探讨聚乙二醇干扰素α-2a联合利巴韦林治疗老年慢性丙型肝炎患者的临床疗效及安全性。方法回顾性分析慢性丙型肝炎患者共77例,年龄≥55岁患者36例为观察组,年龄<55岁患者41例为对照组。给予聚乙二醇干扰素α-2a联合利巴韦林抗病毒治疗,观察病毒学应答、生化学应答及不良反应情况。结果观察组患者快速病毒学应答(RVR)、早期病毒学应答(EVR)、治疗结束时病毒学应答(ETVR)、第12、24、48周时持续病毒学应答(SVR12、SVR24、SVR48)分别为80.6%、93.5%、96.7%、80.6%、80.6%、64%;对照组患者RVR、EVR、ETVR、SVR12、SVR24、SVR48分别为85%、92.5%、92.5%、90%、85%、87.5%,两组SVR48相比差异有统计学意义(P<0.05)。不良反应中,乏力发生率观察组为94.4%,对照组为73.2%,两组相比差异有统计学意义(P<0.05);精神症状发生率观察组为30.6%,对照组为12.2%,两组相比差异有统计学意义(P<0.05)。生化学应答及其他不良反应发生率无统计学差异(P>0.05)。结论老年慢性丙型肝炎患者,使用常规剂量的聚乙二醇干扰素及利巴韦林,在控制基础病基础上,只要能够积极预防,早期发现,及时治疗,多数患者能够坚持完成治疗,仍可获得较高的有效率和较好的耐受性。     

干扰素中和抗体对慢性乙型肝炎抗病毒应答的影响

目的观察干扰素中和抗体(NA)对重组α干扰索(rIFN-α)治疗慢性乙型肝炎时病毒学应答的影响。方法181例经肝穿刺活检证实的慢必乙型肝炎患者，给予rIFN-α 1b治疗，每次5MU，每周3次，疗程6～37个月(中位数10个月），疗程中每1～3个月以抗病毒生物中和法检测NA、以聚合酶链反应荧光定量测定HVV DNA、以Abbott EIA试剂检测乙型肝炎e抗原。结果NA产生率为33.7％。阳性者治疗结束时完全应答率显著低于阴性者(27.9％对45.0％，x^2=4.979，P=0.026)，NA出现时间对疗效无显著影响，但NA出现时已获部分应答者(35例)完全应答率显著高于未获部分应答者(26例)(45．7％对3．8％，x^2=11．009，P=0.001)，NA出现时血清HBV DNA水平低于20pg／ml且近3个月下降幅度超过60％者(16例)完全应答率显著高于NA出观时血清HBV DNA水平高于20pg／ml或虽低于20Pg／ml但近3个月下降幅度不足60％者(45例)(56．3％对20．0％，x^2=7.457，P=0．006)。结论NA可削弱或抵消rIFN-α抗HBV应答，NA出现时已获部分应答者及血清HBV DNA水平低于20pg／ml且近3个月下降幅度超过60％者完全应答率较高。     

长效干扰素治疗慢性丙型肝炎的研究进展

α-干扰素是治疗慢性丙型肝炎的基本药物,但是应用α-干扰素单一疗法的治疗终末病毒应答率只有30％左右,持续病毒应答率仅约10％。α-干扰素和利巴韦林联合治疗可使治疗终末病毒应答率提高至50％左右,但持续病毒应答率也仅约为40％[1]。增加干扰素剂量或给药次数可使治疗期间的HCV RNA阴转率有所提高,但停药、减量或减少     

α—干扰素治疗慢性肝炎中和抗体产生影响因素的探讨

目的：探讨可能影响α-干扰素（INF－α）中和抗体（NA）产生的有关因素,方法：采用抗病毒中和生物测定法（ANB）检测116例INF－α治疗的慢性病毒性肝炎患者血清中的NA。结果：INF－α治疗前ALT（基础ALT）高水平组NA阳性率明显低于基础ALT低水平组（P＜0．05）,病毒阴率则高于后者（P＜0．05）。而乙型肝炎与丙肝炎、男性与女性、年龄高低三者各NA阳性率也分别有所不同,但均无统计学差异（P＞0．05）。结论NA的产生与患者感染病毒类型（乙或丙肝病毒)万籁 别差异及年龄高低无明显关系,但与基础ALT水平的高低有关,基础ALT高水平者NA产生率较,IFN低效好,此有助于IFN治疗的临床病例选择。     

聚乙二醇干扰素与普通干扰素治疗慢性丙型肝炎的疗效比较及其影响因素分析

<正>丙型肝炎病毒(HCV)感染具有隐匿性,无论是急性还是慢性HCV感染都缺乏明显的症状和体征,急性HCV感染慢性化比率高达50%~85%[1],如不及时治疗,慢性感染可致肝脏炎症坏死和纤维化,进而发展为肝硬化、肝癌,将严重危害患者的生命健康和生活质量,使治疗成本大幅上升,给社会造成沉重的负担。慢性丙型肝炎(CHC)主要应用干扰素联合利巴韦林(RBV)治疗。我们回顾性分析了339例接受抗病毒治疗     

Development of anti-interferon antibodies and breakthrough hepatitis during treatment for HCV infection in haemophiliacs

The development of anti-interferon antibodies may lead to treatment failure during interferon therapy. We have studied the development of such antibodies in a group of 39 haemophiliacs receiving interferon-α2a for chronic hepatitis C virus (HCV) infection.   Anti-interferon antibodies developed in five (13%) patients and were associated with 'breakthrough hepatitis' in three cases. There was an association between the development of anti-interferon antibodies and infection with HCV genotype 3a ( P = 0 .01). This study suggests that the development of anti-interferon antibodies may lead to treatment failure in a proportion of haemophiliacs with HCV infection. The association with genotype 3a has not previously been reported. Monitoring for the development of breakthrough hepatitis due to anti-interferon antibodies may provide the opportunity to develop strategies to overcome their effects.     

Virus‐neutralizing antibodies to hepatitis C virus

For a long time, the lack of an appropriate cell culture system has hampered the study of neutralizing antibody responses against hepatitis C virus (HCV). However, the last decade has seen the development of several model systems that have significantly advanced our understanding of viral entry and antibody neutralization. Studies of acutely infected patients suggest that a strong and early production of neutralizing antibodies may contribute to control the virus during the acute phase of HCV infection and facilitate viral elimination by cellular immune responses. It also emerges that the early antibody response mainly targets hypervariable region 1 (HVR1) of the envelope glycoprotein E2. This host response can lead to viral escape from neutralization by rapid amino acid changes in this hypervariable region. In contrast, cross‐reactive neutralizing antibodies seem to appear later during HCV infection, and several mechanisms contribute to reduce their accessibility to their cognate epitopes. These include the masking of major conserved neutralizing epitopes by HVR1, specific N‐linked glycans and the lipid moiety of the viral particle. Other potential mechanisms of evasion from the neutralizing antibody response include a modulation by high‐density lipoproteins and interfering antibodies as well as the capacity of the virus to be transferred by cell‐to‐cell contacts. Finally, the recent identification of several highly conserved neutralizing epitopes provides some opportunities for the design and development of vaccine candidates that elicit a protective humoral immune response.     

Ischemic colitis during interferon-alpha treatment for chronic active hepatitis C

Between 1991 and 1994, at Hoshigaoka Koseinenkin Hospital, we treated 280 patients with chronic hepatitis C with interferon (IFN), and ischemic colitis occurred in two patients (0.7%) during the treatment. Melena appeared in case 1 in the 2nd month after the initiation of IFN-alpha treatment, and in case 2 in the 6th month. In both patients, longitudinal ulcerations in the descending colon were revealed by urgent colonoscopy, and these resolved within 2 weeks after discontinuation of the IFN treatment. It appears that ischemic colitis was associated with the IFN treatment, suggesting that attention should be paid to this possible complication.     

Neutralizing antibodies to recombinant alpha-interferon and response to therapy in chronic hepatitis C virus infection

ABSTRACT— Forty-seven patients with chronic hepatitis C were treated with recombinant interferon alpha-2a (rIFNα2a) given subcutaneously in a standard dose of 3 MU thrice weekly for 12 months. Stored baseline sera and monthly samples during treatment were assayed for anti-interferon neutralizing antibodies using the antiviral neutralization bioassay against 5 IU of rIFNα2a. During therapy, 15 of 47 patients (31.9%) developed detectable levels of neutralizing antibodies within 2–8 months after starting treatment. After 12 months of therapy, 26 of 32 antibody-negative patients (81.3%) showed normalization or marked reduction of ALT levels compared to 4 of 15 (26.6%) who developed anti-IFN neutralizing antibodies (p = 0.0009). Four patients demonstrated antiviral response during treatment even in the presence of low levels or late occurrence of neutralizing antibodies. Six of the seven patients who had disease reactivation after an initial response developed high titers of neutralizing antibodies. Our results suggest that reactivation of chronic hepatitis C before completion of therapy seems to be an obvious consequence of anti-IFN neutralizing antibody formation.     

Human leucocyte interferon-alpha in the treatment of chronic hepatitis C

AIM: To assess the efficacy of different schedules of human leucocyte interferon alpha in chronic hepatitis C. PATIENTS AND METHODS: A total of 213 naive patients with chronic hepatitis C were treated with 4 different schedules of human leucocyte interferon alpha. Sustained response was defined as persistently normal alanine amino transferase values with negative serum hepatitis C virus-RNA up to 12 months after therapy withdrawal. RESULTS: Rates of sustained response were 16% with 3 MU tiw for 6 months, 33% with 6 MU tiw for 5 months after a priming dose of 9 MU tiw for a month, 32% with 3 MU tiw for 12 months and 20% with 3 MU daily for 6 months. The major factors affecting the response rate were age and the hepatitis C virus genotype, as a sustained response was significantly higher in patients under 45 years and infected by hepatitis C virus types other than hepatitis C virus-1. Treatment was well tolerated and side-effects and drop-out events were similar to those described with other types of alpha-interferons. CONCLUSIONS: Human leucocyte interferon alpha appears to be equivalent to recombinant interferon-alpha in the treatment of chronic hepatitis C.     

Efficacy of interferon-alpha treatment in Japanese children with chronic hepatitis C

BACKGROUND: We investigated the efficacy of natural interferon (IFN)-alpha treatment in 34 Japanese children with chronic hepatitis C. METHODS: Thirty-four children completed 6 months of therapy with natural IFN-alpha and were followed for 12 months or longer. We examined the serum hepatitis C virus (HCV) RNA titer and liver histology before, during, and after IFN treatment. RESULTS: At 6 months after the cessation of IFN-alpha treatment, 16 patients (47%) had normal serum alanine aminotransferase concentration and no detectable serum HCV RNA. There were no major side-effects, excluding some influenza-like symptoms during the IFN-alpha treatment. Most genotype 2a patients had a complete response (80%). Moreover, patients who had a low HCV RNA titer (<102 copies/mL) after 1 month of IFN-alpha treatment became complete responders at 6 months after the cessation of treatment. Histological improvement was observed in almost all patients after IFN-alpha treatment. CONCLUSION: Interferon-alpha treatment is safe and effective for children with chronic hepatitis C and has no serious side-effects. A HCV RNA concentration of <102 copies/mL after 1 month of IFN-alpha treatment and genotype 2a may be useful predictors of long-term IFN efficacy.     

HCV基因型对慢性丙型肝炎干扰素疗效的影响

目的 探讨HCV基因型对慢性丙型肝炎的干扰素（IFN）治疗效果的影响。方法 采用随机、开放和对照的多中心临床试验设计。208例受试者按1：1随机分到聚乙二醇干扰素α—2a(Peg-IFN）组和IFN-α-2a组。在治疗之前，用Simmonds基因分型法酶切分型，在治疗24周结束和完成24周的随访后检测患者的ALT和HCV RNA，以HCV RNA的阴转率作为主要评价指标，经ITT人群的统计学分析。结果 202例患者确定了HCV基因型，基因1型158例（78.2%），非基因1型44例（21.8%），治疗结束病毒应答率（ETVR）和持续病毒应答率（SVR）基因1型患者分别为53.8%和25.3%，非基因1型患者分别为61.4%和43.2%，SVR两组患者差异有显著性，x^2=5.313,P=0.021。Peg IFN组基因1型和非1型患者的ETVR分别为76.8%和81.0%，SVR分别为35.4%和66.7%，SVR两组患者差异有显著性，x^2=6.735,P=0.01。病毒复发率基因1型和非基因1型患者分别为55.6%和23.5%，差异有显著性，x^2=5.496,P=0.02.IFN-α-2a组，ETVR和SVR基因1型患者分别为29.0%和14.5%，非基因1型患者分别43.5%和21.7%，差异无显著性。病毒复发率基因1型患者为72.7%，非基因1型患者为50.0%，差异无显著性。结论 IFN对基因1型丙型肝炎患者的疗效低于非基因1型，HCV基因型主要影响IFN对慢性丙型肝炎的持续应答，也与药物和IFN的疗程相关。     

Pioglitazone in chronic hepatitis C not responding to pegylated interferon-alpha and ribavirin

BACKGROUND/AIMS: Insulin resistance reduces the response to interferon alfa-based therapy of chronic hepatitis C patients. It has been speculated that improvement of insulin sensitivity might increase the chances of responding to treatment of such individuals. METHODS: We started a multicenter clinical trial of retreatment of chronic hepatitis C patients, who had failed to respond to the pegylated interferon alfa/ribavirin combination, with a triple therapy consisting in these same antivirals plus an insulin-sensitizer (pioglitazone) (The INSPIRED-HCV study). RESULTS: None of the first five patients fulfilling the inclusion criteria and included in the trial achieved a satisfactory virological response after 12 weeks of retreatment, despite the fact that in at least three of them the insulin resistance score improved. As a result, the study was terminated. CONCLUSIONS: Different schedules are warranted to improve insulin sensitivity prior to attempting retreatment of chronic hepatitis C patients with insulin resistance.     

聚乙二醇干扰素治疗慢性丙型肝炎诱发糖尿病酮症1例及文献回顾

目前,聚乙二醇干扰素联合利巴韦林已成为治疗慢性丙型肝炎的标准方案。本文报道1例男性慢性丙型肝炎患者,在使用标准治疗24周时,出现了1型糖尿病及酮症。