影响2.57亿人的疾病需要更好的治疗

StephenW

Cure for Hepatitis B Pushed
Disease affecting 257 million people needs better treatment

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    by Ed Susman, Contributing Writer, MedPage Today
    April 10, 2019

    This article is a collaboration between MedPage Today® and: Medpage Today

VIENNA – The International Liver Conference kicked off here today with a push to find a cure – not just maintenance treatment – for the one quarter billion people living with hepatitis B virus (HBV) infection, but researchers said that finding a cure could be elusive, and it certainly won't come quickly.

"I think we are still at least 3 years away from starting a Phase III clinical trial that would probably include a combination therapy," said Massimo Levrero, PhD, a member of the governing body of the International Coalition to Eliminate HBV (ICE-HBV) and director of the Cancer Research Centre of Lyon in France.

Levrero, one of several participants in a press conference at the start of the 5-day annual meeting of the European Association for the Study of the Liver, told MedPage Today that there are numerous drug treatment candidates being tested to attack various structures of the virus, but he compared HBV to HIV rather than hepatitis C virus – for which an 8-week functional cure is now available.

"Hepatitis B is very different than hepatitis C, and it is very difficult to eradicate, as is HIV," he said.

While HIV eradication is very rare – with only two known and verified cures worldwide, hepatitis B has been cured by various methods – but in less than 10% of cases, said Peter Revill, PhD, senior medical scientist at the Victorian Infectious Diseases Reference Laboratory in Melbourne, Australia. At the press conference, Revill suggested that as many as one million people in the world have been cured of hepatitis B – but there are an estimated 257 million people living with hepatitis B infection.

Revill said that more than 887,000 deaths are caused by the virus every year. Chronic HBV causes almost 40% of cases of hepatocellular carcinoma, which is the second leading cause of cancer-related mortality worldwide. The most affected areas of the world for hepatitis B infection are Africa and Asia, but the disease is found throughout the world.

He noted that antivirals can suppress the virus but do not affect the risk of causing liver cancer. Levrero said that when people have to take drugs for long periods of time – sometimes decades in the case of HBV treatment – there is a waning of compliance, which makes the need for a cure more imperative.

The ICE-HBV initiative was the subject of a think tank discussion as well as the press briefing; the conference was expected to attract 8,000 physicians, researchers, scientists, and allied healthcare professionals. Along with its presentation, the strategy was published simultaneously online in The Lancet Gastroenterology & Hepatology.

'Global Public Health Challenge'

"Chronic HBV infection is a global public health challenge on the same scale as tuberculosis, HIV, and malaria," Revill and colleagues said. "ICE-HBV is a coalition of experts dedicated to accelerating the discovery of a cure for chronic hepatitis B. Following extensive consultation with more than 50 scientists from across the globe, as well as key stakeholders including people affected by HBV, we have identified gaps in our current knowledge and new strategies and tools that are required to achieve HBV cure."

"We believe that research must focus on the discovery of interventional strategies that will permanently reduce the number of productively infected cells or permanently silence the covalently closed circular DNA in those cells, and that will stimulate HBV-specific host immune responses which mimic spontaneous resolution of HBV infection," the team continued. "There is also a pressing need for the establishment of repositories of standardized HBV reagents and protocols that can be accessed by all HBV researchers throughout the world."

Revill noted that although vaccination against HBV is effective, vaccination cannot eradicate the disease in people who are already infected: "Once chronic infection is established, patients are exposed to significant risk of liver disease including chronic hepatitis, cirrhosis, and hepatocellular carcinoma," he said. "The natural history of chronic HBV infection usually consists of up to five stages, which differ in the level of viral replication, viral antigen expression, and inflammatory activity in the liver."

The investigators concluded: "The time for development and implementation of a safe, affordable, widely available cure for chronic hepatitis B virus infection is now. HBV research funding has for too long been woefully inadequate; this must be addressed. ICE-HBV seeks to achieve its goals by fostering collaborative partnerships with researchers (both within the HBV field and outside), clinicians, the pharmaceutical industry, and a range of stakeholders, including communities affected by chronic hepatitis B; we invite these groups to join forces with ICE-HBV in a global effort to discover, develop, test, and implement HBV cure strategies, to help ensure that the WHO goal of HBV elimination as a public health threat by 2030 is achieved."

The research was supported by the Australian Academy of Science, France Recherche (ANRS), and the Peter Doherty Institute for Infection and Immunity, and supported in part by the intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases.

Revill disclosed relevant relationships with Gilead Sciences; Levrero reported relevant relationships with Bristol-Myers Squibb, ContraVir, Galapagos, Arbutus, Gilead, Janssen, Roche, and MSD.

StephenW

治疗乙型肝炎
影响2.57亿人的疾病需要更好的治疗

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作者：艾德苏斯曼，特约撰稿人，MedPage Today
2019年4月10日

本文是MedPageToday®与Medpage Today的合作

维也纳 - 国际肝脏会议今天在这里拉开帷幕，推动为25亿乙型肝炎病毒（HBV）感染者中的一个找到一种治疗方法，而不仅仅是维持治疗，但研究表明寻找治疗方法可能是难以捉摸的，它肯定不会很快到来。

“我认为我们距离开始可能包括联合治疗的III期临床试验还有至少3年的时间，”国际消除HBV联盟（ICE-HBV）管理机构成员Massimo Levrero博士说。和法国里昂癌症研究中心主任。

Levrero是欧洲肝脏研究协会为期5天的年会开始时的新闻发布会的几位参与者之一，他告诉MedPage Today，有许多药物治疗候选人正在接受测试以攻击各种病毒结构但他将HBV与艾滋病病毒进行了比较，而不是丙型肝炎病毒 - 现在已有8周的功能性治疗方法。

他说：“乙型肝炎与丙型肝炎非常不同，艾滋病毒也很难根除。”

虽然艾滋病毒的根除非常罕见 - 世界上只有两种已知和经过验证的治疗方法，乙型肝炎已通过各种方法治愈 - 但只有不到10％的病例，维多利亚传染病参考实验室的高级医学博士Peter Revill博士说。在澳大利亚墨尔本。在新闻发布会上，Revill表示世界上有多达一百万人已经治愈乙型肝炎 - 但估计有2.57亿人患有乙型肝炎感染。

Revill说，每年有超过88.7万人死于这种病毒。慢性HBV引起近40％的肝细胞癌病例，这是全球癌症相关死亡的第二大原因。世界上受感染最严重的乙型肝炎感染地区是非洲和亚洲，但这种疾病遍布全世界。

他指出，抗病毒药物可以抑制病毒，但不会影响导致肝癌的风险。 Levrero说，当人们不得不长期吸毒 - 在HBV治疗的情况下有时需要数十年 - 但是依从性逐渐消失，这使得治疗的必要性变得更加迫切。

ICE-HBV倡议是智囊团讨论和新闻发布会的主题;该会议预计将吸引8,000名医生，研究人员，科学家和专职医疗保健专业人士。除了介绍之外，该策略还在“柳叶刀胃肠病学和肝脏病学”网站上同时发布。

'全球公共卫生挑战'

“慢性HBV感染是与结核病，艾滋病毒和疟疾同等规模的全球公共卫生挑战，”Revill及其同事说。 “ICE-HBV是一个致力于加速发现慢性乙型肝炎治疗方法的专家联盟。在与来自全球的50多位科学家以及包括受HBV影响的人等主要利益相关者进行更广泛的磋商之后，我们发现了差距在我们目前的知识和实现HBV治愈所需的新策略和工具中。“

“我们认为，研究必须集中在发现介入策略，这些策略将永久性地减少有效感染细胞的数量或残留沉默这些细胞中共价闭合的环状DNA，并且这将刺激HBV特异性宿主免疫反应，模仿自发消化HBV感染，“该团队继续说道。 “迫切需要建立标准化HBV试剂和方案的储存库，全世界所有HBV研究人员都可以使用这些储存库。”

Revill指出，尽管接种HBV疫苗是有效的，但疫苗接种不能根除已经感染的人的疾病：“一旦确定慢性感染，患者就会面临肝病的重大风险，包括慢性肝炎，肝硬化和肝细胞癌，”他“慢性HBV感染的自然病史通常包括多达五个阶段，其病毒复制水平，病毒抗原表达和肝脏炎症活动不同。”
研究人员得出结论：“现在是制定和实施安全，负担得起，广泛可用的慢性乙型肝炎病毒感染治疗方法的时候了。长期以来，HBV的研究资金严重不足;必须加以解决.ICE-HBV寻求通过促进与研究人员（包括HBV领域和外部），临床医生，制药行业以及一系列利益相关者（包括受慢性乙型肝炎影响的社区）的合作伙伴关系来实现其目标;我们邀请这些团体与ICE-HBV合作全球努力发现，开发，测试和实施HBV治疗策略，以帮助确保实现世卫组织到2030年消除HBV作为公共卫生威胁的目标。“

该研究得到了澳大利亚科学院，法国Recherche（ANRS）和Peter Doherty感染和免疫研究所的支持，部分得到了国家糖尿病，消化和肾脏疾病研究所的校内研究计划的支持。

Revill透露与Gilead Sciences的相关关系; Levrero报告了与Bristol-Myers Squibb，ContraVir，Galapagos，Arbutus，Gilead，Janssen，Roche和MSD的相关关系。

    主要资源
    柳叶刀胃肠病学和肝脏病学
    来源参考文献：Revill P等，“治疗乙型肝炎的全球科学策略”Lancet Gastroenterol Hepatol 2019; DOI：10.1016 / S2468-1253（19）30119-0。