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转载 口服疗法治疗丙型肝炎前景光明

贺新春 副主任医师 湖南省人民医院 感染科
2013-09-24 591人已读
贺新春 副主任医师
湖南省人民医院
Investigational Oral Regimen for Hepatitis C Shows Promise
口服疗法治疗丙型肝炎前景光明

Aug. 27, 2013 — In a study of an all-oral drug regimen, a majority of volunteers with liver damage due to hepatitis C virus (HCV) infection were cured following a six-month course of therapy that combined an experimental drug, sofosbuvir, with the licensed antiviral drug ribavirin. The results showed that the regimen was highly effective in clearing the virus and well tolerated in a group of patients who historically have had unfavorable prognoses.湖南省人民医院感染科贺新春

2013827消息:在一项全口服药物治疗方案的研究中,因丙肝病毒(HCV)感染而肝损伤的志愿者,在经过6个月的一次疗程(一种实验性药物sofosbuvir与已上市的抗病毒药利巴韦林联合给药)后,大多数都得到了治愈。这些结果表明,该方案可高度有效地清除丙肝病毒,且对一群具有不良预后史的患者具有良好耐受。

Scientists from the National Institute of Allergy and Infectious Diseases (NIAID) and the NIH Clinical Center, parts of the National Institutes of Health, led the Phase II trial. The findings appear in the Aug. 28 issue of the Journal of the American Medical Association (JAMA).
美国国立卫生研究院(NIH)下属的国立过敏和传染病研究所(NIAID)NIH临床中心的科学家,领导了这项2期试验。研究结果发表在828发行的《美国医学会杂志(JAMA)上。
More than 3 million Americans have chronic HCV infection, a condition that is a major cause of cirrhosis (liver tissue scarring) and liver cancer, and a leading reason for liver transplantation. Deaths from HCV-related liver disease number about 15,000 every year. Standard treatment for HCV can last up to a year and usually involves weekly injections of pegylated interferon-alpha given with the oral drug ribavirin and an HCV protease inhibitor. Side effects from this treatment can be severe, notably from interferon-alpha, and can include depression, flu-like symptoms and anemia.
超过300万美国人患有慢性HCV感染,该疾病是导致肝硬化(肝组织疤痕)和肝癌的主要元凶,也是导致肝移植的第一元凶。每年约15000人死于HCV相关的肝病。HCV的标准疗法可能需要持续长达一年,通常涉及每周一次注射聚乙二醇α-干扰素及口服利巴韦林与一种HCV蛋白酶抑制剂。该治疗产生的副作用可能非常严重,特别是α-干扰素产生的副作用,并有可能包括抑郁流感样症状和贫血在内的副作用。
"There is a pressing need for hepatitis C virus treatments that are less burdensome to the patient, have fewer side effects and take less time to complete. Building on previous work, this trial provides compelling evidence that interferon-free regimens can be safe and effective," said NIAID Director and study co-author Anthony S. Fauci, M.D.
NIAID
主任、共同研究作者Anthony S. Fauci医学博士说:迫切需要那些病人负担较轻、副作用较少且疗程较短的丙肝病毒疗法。基于之前的工作,该试验提供了令人信服的证据,证明无干扰素方案可能安全有效。
The current study involved 60 volunteers with genotype-1 HCV, which tends to be less responsive to interferon-based treatment. Fifty of the 60 participants were African-American.
目前的研究涉及60名患有基因型-1 HCV志愿者,他们往往对干扰素为基础的治疗反应不灵敏。其中50名参与者为非裔美国人。
"While African-Americans make up about 13 percent of the U.S. population, they represent more than 22 percent of people with chronic HCV infection and, compared to whites, have lower cure rates with traditional HCV therapy," said NIAID researcher Shyam Kottilil, M.D., Ph.D., the principal investigator of the trial. "Several recently completed trials testing interferon-free regimens have yielded promising results, but most volunteers in those studies were white."
该试验首席研究员、NIAID研究员Shyam Kottilil(M.D.Ph.D学位)表示:虽然非裔美国人占美国人口的约13%,但他们却占慢性HCV感染人群的22%多,使用传统HCV疗法治疗,其治愈率要低于白人患者。最近完成的几项试验测试了无干扰素方案,结果令人满意,但这些研究中的大多数志愿者都是白人。
The new study also differs from many previous trials because it enrolled people with severe liver damage as well as those with mild or moderately scarred livers.


与许多以往试验相比,这项新研究的另外不同在于其招募了严重肝损伤患者及轻度或中度肝疤痕患者。

The study was divided into two parts. The first part enrolled 10 people with mild or moderate liver fibrosis. Volunteers received oral ribavirin at a dosage based on their weight along with the experimental drug sofosbuvir, also in pill form, taken daily for six months. Gilead Sciences, Inc., of Foster City, Calif., manufactures sofosbuvir and supplied it to the study physicians.
这项研究分为两部分。第一部分招募了10例轻度或中度肝纤维化患者。志愿者口服接受利巴韦林,剂量基于其体重进行调节,同时服用一种实验性药物sofosbuvir(也是片剂),每日一次,服用6个月。由位于加州福斯特市的吉利德科学公司生产sofosbuvir并提供给研究医生。
Nine volunteers completed the course of therapy. Virus was undetectable in all nine volunteers 12 weeks after the end of therapy and continued undetectable when they were tested again 24 weeks after finishing therapy. HCV does not integrate itself into human DNA. If the virus cannot be detected for a period of 12 weeks after stopping therapy, the patient is considered cured, Dr. Kottilil said.
9名志愿者完成了该疗程。在治疗结束后12周,所有9名志愿者体内都检测不到该病毒,进而在治疗结束的24周后再次进行检测,仍检测不出。HCV本身并不会与人DNA发生结合。Kottilil博士表示,如在治疗停止后12周,无法检出该病毒,则可认为该患者得到了治愈。
The second part of the trial enrolled 50 volunteers, 13 of whom had liver damage rated as serious. Twenty-five received ribavirin based on their weight, and 25 received a low dose (600 milligrams per day). All received sofosbuvir.
试验的第二部分招募了50名志愿者,其中13人被定为严重肝损伤患者。其中25名接受剂量基于其体重进行调节的利巴韦林,而另25名则接受低剂量利巴韦林(600mg每日)。所有志愿者都接受sofosbuvir
"Because ribavirin can cause serious side effects, including anemia, we wanted to compare response rates in patients taking low-dose ribavirin with results from patients on a weight-based dosage," said Dr. Kottilil.
Kottilil
博士表示:由于利巴韦林可能会导致包括贫血在内的严重副作用,所以我们希望将服用低剂量利巴韦林患者的有效率与服用剂量基于体重调节的患者的结果进行比较。
At four, 12 and 24 weeks after the end of treatment, volunteers were tested for the presence of HCV. HCV levels were undetectable in 24 of the volunteers in the weight-based arm when treatment ended. Of those, 17 continued to have undetectable virus levels 24 weeks later and were considered cured of infection. In the low-dose arm, three volunteers dropped out of the study. Of the remaining 22, all responded to the treatment, but only 12 were considered cured at 24 weeks after the end of treatment.
分别在治疗结束后的41224周检测HCV。基于体重组在治疗结束时,有24名志愿者检测不到HCV水平。其中17名在随后第24周仍未检出病毒水平,进而可认为感染得到治愈。在低剂量组,有3名志愿者退出了研究。其余22名都对治疗产生反应,但在治疗结束后第24周,只有12名被认为得到治愈。
"We saw an overall cure rate of about 70 percent using regimens that did not include interferon," said Dr. Kottilil. "This is an encouraging result, especially considering the proportion of volunteers who had characteristics -- such as being male, having HCV genotype-1 infection, being African-American and having advanced liver damage -- that are recognized as predictors of poor response to treatment."
Kottilil
博士表示:我们看到,使用不含干扰素的方案,其总治愈率约70%。该结果令人鼓舞,特别是考虑到相当大比例志愿者具有如下特征:如男性、患有HCV基因型-1感染、非裔美国人及患有晚期肝损伤,这些特征被认为是治疗反应差的预测指标。
Additional trials are underway to further determine if regimens without interferon or ribavirin can help people with chronic HCV infection, particularly those who have both HIV and HCV infections, said Dr. Kottilil. These trials include two studies in which volunteers with or without HIV infection take a combination of HCV drugs (but no interferon or ribavirin) for periods of three months or less. Information about these trials is available at clinicaltrials.gov using the identifiers NCT01805882 and NCT01878799.


Kottilil博士表示,为确定不含干扰素或利巴韦林的治疗方案对慢性HCV感染患者,特别是同时感染HIVHCV的患者是否有效,目前正在进行其他试验。这些试验包括两个研究,在研究中,患有HIV感染或无HIV感染的志愿者服用多种HCV药物(但不含干扰素或利巴韦林),疗程为3个月或3个月不到。请登陆clinicaltrials.gov并使用识别号NCT01805882 NCT01878799获取这些试验的信息。

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贺新春 副主任医师

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