以血清HBV DNA作为治疗慢性HBV评估疗效的指标

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以血清HBV DNA作为治疗慢性HBV感染过程中评估疗效的指标
文献综述和分析
2003-07-15
HEPATOLOGY, Vol. 37, No. 6, 2003




　　目前，评估治疗慢性乙肝病毒（HBV）感染的药物时都是采用肝组织学检查作为主要的疗效评估终点。但是由于序列肝活检在实际工作中受到限制，需要寻找一种在更短时间内评估疗效的替代指标。考虑到在HIV和HCV感染时病毒复制和疾病进展直接相关，所以我们希望探究一下在HBV感染时是否也存在同样的相关性。我们回顾了文献并进行分析以研究HBV DNA的绝对变化和治疗后变化与其他被认可的疾病活动性指标间的关系。总共有26项前瞻性研究符合我们的入选标准。研究中包括核苷拟似物和/或干扰素方组案和对照组。我们发现在病毒载量变化与组织学积分等级、生化学和血清学反应间存在着有统计学意义的一致联系。我们的分析提示治疗介导的HBV DNA下降可用于评估疗效。而且我们观察到定量HBV DNA比组织学检查的动力学范围更广，可以显示两种效力不相当的治疗间的差别。分析显示当HBeAg阳性病人使用核苷拟似物时这种相关性更强。总之，抗HBV治疗的目的是要持久抑制病毒。还需要进行其他的前瞻性研究来更准确地确定将病毒抑制到何种程度比较合适。

Serum HBV DNA as a Marker of Efficacy During Therapy for Chronic HBV Infection: Analysis and Review of the Literature

Currently, compounds under evaluation for treatment of chronic hepatitis B virus (HBV) infection are evaluated with liver histology as the primary end point for efficacy. However, because of practical limitations in serial liver biopsies, there is a need for alternate markers to assess efficacy over shorter periods of time. Considering the direct correlation between viral replication and disease progression during human immunodeficiency virus and hepatitis C virus infection, we explored whether such a correlation exists for HBV infection. We reviewed the literature and conducted an analysis to investigate the relationship between absolute or treatment-induced changes in HBV DNA levels and other accepted markers of disease activity. A total of 26 prospective studies met our selection criteria, including 33 evaluable treatment arms. The study treatments consisted of nucleosides and/or interferon regimens and control arms. We found statistically significant and consistent correlations between viral load level or change and histologic grading and biochemical and serologic response. Our analysis suggests that a treatment-induced reduction in HBV DNA level can be used for assessing efficacy of treatment regimens. Further, we observed that quantitative HBV DNA has a broader dynamic range than histology, allowing demonstration of differences between 2 active treatments of unequal potency. The analysis showed stronger results in studies using nucleoside regimens and in hepatitis B e antigen (HBeAg)-positive patients. In conclusion, the goal of anti-HBV therapy should be profound and durable viral suppression, as defined by very sensitive assays. Additional prospective studies are needed to precisely determine the desirable level of viremia to attain.

[此贴子已经被作者于2004-4-2 23:20:56编辑过]