慢乙肝全程管理与个体化治疗讲述.ppt

我国专家建议Roadmap * SPEAKER NOTES The primary objective of this analysis was to determine the effects of at least three years of ETV treatment on necroinflammation and fibrosis among nucleoside-na?ve HBeAg-positive and negative patients. Thus the co-primary endpoints for this analysis were: Histologic improvement compared to baseline. Histologic improvement was defined as a greater than or equal to 2 point decrease in Knodel necroinflamatory score and no worsening of Knodell fibrosis score. Improvement in Ishak fibrosis score compared to baseline. For this endpoint, improvement was defined as a greater than or equal to 1 point decrease in Ishak fibrosis score. Ref 19 Chang TT等的研究了57例HBeAg阳性和阴性的核苷初治患者，他们接受恩替卡韦治疗至少3年，具有足够的基线与长期活检标本，基线Knodell坏死性炎症评分≥2。长期治疗期间活检中位时间为6年（3~7年）。证实这些初治患者的纤维化或肝硬化获得了实质性的改善或逆转。 * 对持续HBV DNA阳性、达不到上述治疗标准、但有以下情形之一者，亦应考虑给予抗病毒治疗 （1）对ALT大于正常上限且年龄40岁者，也应考虑抗病毒治疗 (III)。 （2）对ALT持续正常但年龄较大者（40岁），应密切随访，最好进行肝活检；如果肝组织学显示Knodell HAI ≥4，或炎症坏死≥G2，或纤维化≥S2，应积极给予抗病毒治疗[59]（II）。 （3）动态观察发现有疾病进展的证据（如脾脏增大）者，建议行肝组织学检查，必要时给予抗病毒治疗（III）。 应用NUC单药治疗的患者应在治疗12周时进行评估，与基线水平相比血清HBVDNA下降小于2log10拷贝／ｍｌ时确定为原发性治疗失败，应当改变治疗方案，如加用效力更强的药物。 This figure is a simple demonstration of what one might see utilizing these different definitions. In a primary nonresponse, as shown in the yellow line, you can see that there is less than a 1 log reduction at the end of 6-12?months. Shown in the green line is a suboptimal response and where there is a reduction in the HBV?DNA, but it does not go to low levels or to undetectability. The blue line is an example of an individual who has virologic breakthrough. First of all, there is a substantial reduction in serum HBV?DNA to very low or undetectable levels, but then over time—for example at Month?12—there is breakthrough, defined as a 1 log increase, that becomes apparent very quickly and this represents failure of therapy after it has initially been begun—what we call “virologic breakthrough.” We want to recognize this early so we can intervene with t