评估慢性乙肝患者进行服液法治疗过程中的依从性

　　问：使用核苷类似物进行治疗的乙肝患者，通过测定药物或其代谢物的血清或尿液中的含量，目前有没有办法来确定患者的治疗没有依从性？

　　鲍尔·马丁：主任医师，纽约西乃山医院Recanati/Miller移植研究所肝病科副主任。

　　答：一般来说，目前采用的治疗乙肝的替代药物，都能很好的兼容负面影响，因此依从性的问题并没有引起人们的注意。虽然不同类似物的效用各异，但是经过一段时间的治疗，大部分患者的HBV DNA都会下降，转氨酶恢复正常。当耐药性已经成为限制长期治疗的一个主要因素，人们已经开始关心该如何预测耐药性。耐药性是指在治疗过程中，血清里面HBV DNA到达最低水平后反弹。抗病毒作用迟钝、耐药性的产生和没有依从性，将这三者区分开是很重要的。目前，对各种口服替代物的血清学测试并没有投放市场，而依从性的确定也仅仅停留在推理的水平。次反应是经过几个月的治疗后，HBV DNA水平不再下降，并应该密切关注，随后的病毒耐药性增强的可能性。使用拉米夫定治疗的患者，经过24周的治疗后，血清中HBV DNA水平大于十的四次方copies/mL，预示着64%的患者病毒变异。使用阿德福韦的患者，在进行治疗的48周之后，血清中HBV DNA大于十的三次方copies/mL，这是病毒变异的显著标志。适用替比夫定治疗，24周后，通过聚合酶链反应检测可以看到长期病毒变异反应。

　　到目前为止，使用恩替卡韦治疗，耐药性很低。但是任何的口服替代物，在服用24-48周后，血清中HBV DNA水平都没有降低，这很明显地预示着没有依从性，而不是治疗的次反应。目前，依从性只能被推断，而不能适用各种技术进行确认。

　　【名词解释】依从性：依从性是指疗养员在疗养期间对医生所制定的疗养康复计划和护理措施的执行情况,它与疗养员对自身所患疾病的认识、重视程度，对生活的态度及对医护人员的信任程度有关。完全执行医嘱的称为依从性好，反之为不好。由于医者、患者等原因造成患者依从性不好，不仅影响患者康复,甚至造成严重后果。

　　原文：

　　Is there any current method available to identify noncompliance in hepatitis B patients who are being treated with one of the nucleot(s)ide analogs by measuring serum or urine levels of the drug or its metabolite?

　　Paul Martin, MD 

　　Professor of Medicine, Associate Director of the Division of Liver Disease, Recanati/Miller Transplantation Institute, Mount Sinai Hospital, New York, NY

　　Generally, the currently approved agents for the treatment of chronic hepatitis B virus (HBV) infection are well tolerated with negligible side effects, so issues of compliance have not received much attention. Although the potency of individual agents varies, initiation of therapy results in a fall in serum HBV DNA and normalization of aminotransferases in most patients after a variable period of time. As resistance has become the major factor limiting long-term treatment response, on-treatment predictors of its emergence have been proposed. Resistance is implied by a rebound in serum HBV DNA 1 log above the nadir of its level during antiviral therapy.It is clearly important to distinguish between a "sluggish" antiviral response, development of resistance, and noncompliance. At present, testing for serum levels of the various oral agents is not commercially available, and confirmation of compliance is by inference only. A suboptimal response is implied by absence of a decline in HBV DNA levels after several months of treatment and should raise concern about an enhanced risk of subsequent viral resistance. In lamivudine-treated patients, a serum HBV DNA level > 104 copies/mL at 24 weeks of therapy predicts subsequent viral resistance in 64% of individuals. In adefovir-treated patients, a serum HBV DNA > 103 copies/mL at 48 weeks of therapy was a significant predictor of subsequent viral resistance. With telbivudine therapy, PCR (polymerase chain reaction) negativity at 24 weeks of therapy has been found to be a reliable predictor of long-term virologic response. To date, treatment of nucleoside-naive patients with entecavir has resulted in a very low rate of antiviral resistance such that predictors of resistance have not been validated. However with any of the oral agents, a complete absence of a decline in serum HBV DNA levels within 24-48 weeks of initiating antiviral therapy strongly implies noncompliance rather than a suboptimal response to treatment. For now, compliance can only be inferred rather than conclusively proven in the absence of our ability to measure therapeutic levels.