忘记表面抗体，如果您有检测不到病毒载量及HBsAg，你可能会

StephenW

Forget Surface Antibodies, If You Have Both Undetectable Viral Load and HBsAg, You Might Be Functionally “Cured”
Posted on March 23, 2016 | 2 Comments
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Dr. Robert Gish

Dr. Robert Gish

By Christine Kukka

For decades, people living with chronic hepatitis B were told they would be “cured” only when they lost the hepatitis B surface antigen (HBsAg) and developed surface antibodies. It represented the holy grail of recovery that everyone hoped for, but very few achieved.

Today, experts are redefining what constitutes a “functional cure” from chronic hepatitis B and taking the surface antibody out of the equation.

Researchers, including expert Dr. Robert Gish, suggest if people have an undetectable viral load (HBV DNA), undetectable HBsAg, and no signs of liver damage, they may be “functionally cured,” even if they haven’t developed surface antibodies. The cure is called “functional” because the only cure for hepatitis B is when the immune system controls or suppresses the virus.

People with chronic hepatitis usually experience several infection stages, starting with a high viral load (called immune-tolerant or immune-trained) during childhood and early adulthood, followed by years and even decades of “active” hepatitis B where the immune system tries to clear the infection, indicated by elevated liver enzyme tests.

In some lucky people, the “active” phase successfully eradicates HBsAg and infected liver cells. They test negative for HBsAg, their viral load drops to undetectable levels and their liver enzyme tests (for ALT or SGPT) show no signs of liver damage. Despite their “inactive” infection, studies show two-thirds of these people will never develop surface antibodies, said Dr. Gish, medical consultant to the Hepatitis B Foundation and professor consultant of gastroenterology and hepatology at Stanford University.

But isn’t developing surface antibodies the gold standard for recovery from hepatitis B? Not any more, explained Dr. Gish. Historically, medical guidelines dictated that chronically-infected patients must generate at least 10 mIU/mL of surface antibodies to be “functionally cured.” That level was used because most adults who had a short-term or acute case of hepatitis B were able to generate lots of surface antibodies once they’ve cleared the infection, and people who were vaccinated also tended to generate high surface antibody levels.

“But we’ve learned that standard is no longer useful for patients who’ve been chronically infected,” Dr. Gish explained. “Hepatitis B surface antibodies are very specific in their mission, and we’re learning that the body may be making other types of surface antibodies that we cannot measure. Today, we’re only measuring one type of surface antibody, and for some reason we don’t know yet, it may never become positive in people who have been chronically infected and cleared HBsAg.

Dr. Gish speculates that the surface antibodies that labs measure may all bind to any HBsAg that remain following infection, so there may not be any excess of this one type of surface antibodies to measure.

It may be similar to what happens in vaccinated people who over time no longer test positive for surface antibodies. “In the old literature, people thought having lots of surface antibodies meant better protection, but now we know people who’ve been vaccinated remain protected by their immune system’s T-cell response and also ‘memory B cells’ even if their surface antibodies decline or become undetectable,” he said.

Bottom line, “immune memory” and antibodies that labs may not be able to identify remain ready to fight infection following vaccination and even after a chronic infection.

As a result of these findings, people who have gone two or more years with undetectable viral load and HBsAg, and no signs of liver damage just might be “functionally cured”, Dr. Gish suggests, even if their surface antibodies remain undetectable. “It’s clearly a new gold standard,” he added, referring to recent studies that found no hepatitis B reactivations in these “inactive” patients who were followed for up to eight years.

However, Dr. Gish cautions, it’s important to remember that once infected with hepatitis B (indicated by presence of the hepatitis B core antibody – anti-HBc), people will always retain low levels of the hepatitis B virus in their bodies — even if they develop surface antibodies. Like the chicken pox virus, the hepatitis B virus remains suppressed only as long as the immune system remains healthy enough to keep it in check. Old age, other illnesses, chemotherapy or drugs that suppress the immune system can allow a reactivation of hepatitis B in the same way that chicken pox returns as “shingles” in older adults. Unfortunately, there is no cure available that totally eradicates all hepatitis B virus from the body.

Today, chronically-infected people can look forward to a new, more accurate benchmark that represents a functional cure: clearing both HBV DNA and HBsAg, and experiencing no liver damage for two or three years. All three goals must be achieved–especially undetectable surface HBsAg–otherwise they remain at risk of reactivation, according to recent studies.

According to Dr. Gish, once patients achieve two or three years of consistently undetectable viral load (HBV DNA below 8-12 IU/mL) and HBsAg levels (below 0.05 IU/mL), they do not require frequent monitoring unless they have a history of cirrhosis or signs of liver damage.

Why has it taken so long for researchers to figure this out? Historically, researchers have focused on patients with active infections that damaged their livers and led to cancer in their search for effective treatments. For the first time, researchers are also monitoring “inactive” patients who clear both HBV DNA and HBsAg and are publishing studies about their long-term outcomes.

StephenW

忘记表面抗体，如果您有检测不到病毒载量及HBsAg，你可能会在功能上“治愈”
发表于2016年3月23日| 2评论
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罗伯特·吉什博士
罗伯特·吉什博士
恭Kukka
几十年来，患有慢性乙型肝炎的人被告知，他们将被“治愈”，只有当他们失去了乙肝表面抗原（HBsAg）和表面开发的抗体。它代表复苏的圣杯，每个人都希望的，但很少实现。
目前，专家们正在重新定义什么是慢性乙型肝炎“功能性治愈”，并采取表面抗体的方程。
研究人员，包括专家罗伯特·吉什博士建议，如果人们有一个检测不到病毒载量（HBV DNA）检测不到乙肝表面抗原和无肝损伤的迹象，他们可能会“治愈功能，”即使他们没有开发表面抗体。因为乙肝唯一的治疗是免疫系统的控制时，或抑制病毒的治疗被称为“功能性”。
患有慢性肝炎的人​​通常遇到几个感染的阶段，从一个高病毒载量（称为免疫耐受或免疫训练）童年和成年早期，随后几年甚至几十年“活动的”乙肝所在的免疫系统会尝试清除感染，升高的肝酶试验表明。
在一些幸运的人，“主动”阶段成功根除HBsAg和感染的肝细胞。他们测试乙肝表面抗原阴性，他们的病毒载量降至检测不到的水平和肝酶测试（用于ALT或SGPT）没有显示肝损伤的迹象。尽管他们“不活跃”的感染，研究显示这些人的三分之二将永远不会发展表面抗体，吉什博士，医学顾问，乙型肝炎基金会，并在斯坦福大学学和免疫学教授顾问说。
不过，这不开发表面抗体乙型肝炎恢复金本位？没有更多的解释吉什博士。在历史上，医疗准则决定了慢性感染患者必须生成表面的抗体的至少10 MIU / mL至是“功能上固化。”这水平使用，因为谁了乙型肝炎的短期或急性情况下大多数成年人能产生大量抗体，表面的，一旦他们清除了感染，谁接种了疫苗的人也往往产生较高的表面抗体水平。
“但我们已经了解到，标准已不再是谁一直在慢性感染患者的，”吉什博士解释说。 “乙肝表面抗体是自己的使命非常明确，我们正在学习，身体可能会作出其他类型的，我们不能测量表面抗体。今天，我们只测量一种类型的表面抗体，出于某种原因，我们还不知道，它可能永远不会成为谁一直在慢性感染和乙肝表面抗原清除人阳性。
基希博士推测该表面的抗体的实验室措施可能所有绑定到任何的HBsAg仍然存在以下的感染，所以可能没有任何过量的这一种类型的表面的抗体来测量。
它可以类似于在接种人谁随时间不再测试正面为表面的抗体会发生什么。 “在旧文学，人们以为有很多表面抗体，意味着更好的保护，但现在我们知道谁一直在接种疫苗仍然受到他们的免疫系统的T细胞反应的保护人，也是”记忆B细胞'，即使它们的表面抗体下降或变成检测不到，“他说。
底线，“免疫记忆”，而实验室可能无法识别抗体随时准备对抗感染接种疫苗之后，甚至慢性感染后。
由于这些发现的结果是，人们谁拥有了两个或更多年的检测不到病毒载量与HBsAg，和无肝损伤的迹象只是可能被“功能治愈”，基希博士建议，即使它们的表面的抗体仍然检测不到。 “这显然是一个新的黄金标准，”他补充说，指的是最近的研究，没有发现乙肝重新激活这些“不活动”谁患者随访长达八年。
，人民将永远保留在他们的身体对乙肝病毒水平低 - 但是，吉什博士提醒，一定要记住，一旦感染乙肝（抗HBc由乙型肝炎核心抗体的存在表示） - 是很重要的，即使他们开发的表面抗体。像水痘病毒，乙肝病毒仍然只要只能作为免疫系统保持足够健康的保持它在检查抑制。年老，其它疾病，抑制免疫系统的化学疗法或药物可允许乙型肝炎的激活中相同的方式，水痘返回如老年人“带状疱疹”。不幸的是，没有任何可用的治愈该完全根除所有B型肝炎病毒从主体。
如今，慢性感染者可以期待一个新的，更准确的基准测试，它代表一个功能治愈：既清除HBV DNA及HBsAg，体验两三年没有肝损伤。所有这三个目标必须实现，特别是检测不到乙肝表面抗原表面，否则它们保持在激活的风险，根据最近的研究。
根据基希博士，一旦患者达到两三年始终不可检测的病毒载量（HBV DNA的低于8-12国际单位/毫升）和HBsAg水平（低于0.05单位/毫升）的，它们不需要频繁的监测，除非他们有一个肝硬化的病史或肝损伤的迹象。
为什么花了这么长的时间研究人员算出这个？历史上，研究人员专注于病人受损的他们的肝脏，并导致癌症在寻找有效的治疗方法积极感染。这是第一次，研究人员也在监控“不活跃”的病人谁同时清除HBV DNA和HBsAg和对他们的长期结果发布研究。