慢性乙型肝炎：新的治疗目标应该是什么？

StephenW

Antiviral Res. 2013 Feb 4. pii: S0166-3542(13)00021-1. doi: 10.1016/j.antiviral.2013.01.006. [Epub ahead of print]
Chronic hepatitis B: What should be the goal for new therapies?
Block TM, Gish R, Guo H, Mehta A, Cuconati A, Thomas London W, Guo JT.
Source

Department of Microbiology and Immunology, Drexel University College of Medicine, 3805 Old Easton Road, Doylestown, PA 18902, United States; Institute for Hepatitis and Virus Research, Pennsylvania Biotechnology Center, 3805 Old Easton Road, Doylestown, PA 18902, United States. Electronic address: [email protected].
Abstract

Chronic hepatitis B can currently be medically managed with either pegylated interferon-alpha (pegIFN-α) or one of the five nucleos(t)ide analog Direct Acting Antivirals (DAAs) that inhibit the hepatitis B virus (HBV) DNA polymerase. While pegIFN-α is effective in approximately one-third of the treated patients, the polymerase inhibitors significantly reduce viral load in the vast majority of those treated. However, neither pegIFN-α nor nucleosi(t)de analogs are capable of reliably eliminating the virus and achieving a cure. Moreover, the interferons and polymerase inhibitors are recommended by US, European and Asian professional society practice guidelines for use in only a subset of those infected with HBV. This subset is the population with the greatest levels of circulating viral DNA and abnormal liver function. Although this is the population at the highest risk for cirrhosis and liver cancer, those who fall outside the treatment guidelines, with low levels of viral replication and normal serum ALTs, may also benefit from antiviral therapy. The questions are thus: are new classes of drugs needed to manage chronic hepatitis B? Is a cure possible? Is a cure even necessary? It is therefore important to define the meaning of a cure and determine what the goals of new therapies should be. In this article, we address those questions and propose two operational definitions of medically attainable cures. The first is a "functional cure" based on the clinical outcome, in which the patient's life expectancy becomes the same as that of an individual who has resolved his HBV infection without therapy. Because such an outcome cannot be measured over the short term, we also define an "apparent virological cure," based on the stable off-drug suppression of HBV viremia and antigenemia and the normalization of ALTs and other laboratory tests. We suggest that such a virological cure should be the goal of future therapeutics in all patients with chronic hepatitis B. The extent to which a virological cure predicts a functional cure will only be determined by long-term follow-up.

StephenW

慢性B型肝炎目前可以医疗管理，无论是聚乙二醇化干扰素-α（pegIFN-α）的核苷（酸）IDE的模拟直接作用抗病毒药物（DAAS），抑制B型肝炎病毒（HBV）DNA聚合酶之一。 pegIFN-α是有效的治疗的患者的约三分之一，聚合酶抑制剂显着减少病毒载量，在绝大多数的那些处理。然而，既不pegIFN-α也不nucleosi的（t）的去类似物的是能够可靠地消除了病毒和实现固化。此外，干扰素和聚合酶抑制剂，由美国，欧洲和亚洲的专业与HBV感染者中只有一小部分用于社会实践指导方针的建议。该子集是人口与水平最高的循环病毒DNA和肝功能异常。虽然这是在肝硬化和肝癌的风险最高的人群，那些，超出治疗指南，低水平的病毒复制和正常人血清中的低价竞标，也可能受益于抗病毒治疗。问题是这样的：新的类管理慢性乙型肝炎的药物吗？治愈的可能吗？是可以治愈甚至是必要的吗？因此，重要的是要界定的意义的一种治疗方法和确定的目标，新的治疗方法应该是什么。在这篇文章中，我们要解决这些问题，并提出了两种操作的医疗可达到治愈的定义。第一种是“功能性治愈”的临床成果的基础上，中，病人的寿命变得一样如果没有接受治疗，他的HBV感染已解决个人。因为这样的结果不能在短期内，我们还定义了一个“明显的病毒学治疗”的基础上的稳定的药物抑制HBV病毒血症和抗原和低价竞标的正常化和其他实验室检查。我们认为，这样的病毒学治疗的目标应当是未来疗法在慢性乙型肝炎患者的病毒学治愈的程度，预测功能的治疗才能确定长期的后续。

咬牙硬挺

如果乙肝病毒变得对人体无伤害，携带一辈子又如何？