慢性乙型肝炎患者YMDD自然变异的临床观察

目的观察发生YMDD自然变异的慢性乙型肝炎（CHB）患者的临床特征，探讨HBVYMDD自然变异发生的可能机理，为CHB抗病毒治疗提供新思路。方法选择144例HBVDNA阳性、未经抗病毒治疗的CHB患者作为观察对象，采用PCR熔解曲线法检测其YMDD基因序列突变；同时对其进行HBVDNA定量、血清丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）和乙肝两对半等相关指标检测，并对患者性别、年龄及上述检测结果进行统计学分析。结果144例未经抗病毒治疗的CHB患者中，有30例出现YMDD自然变异，变异检出率为20．8％，其中YIDD阳性19例（占63．3％），YVDD阳性8例（占26．7％），YIDD＋YVDD同时阳性3例（占10％）。YMDD自然变异组CHB患者年龄明显小于未变异组；HBVDNA定量值在105copies／ml以上的CHB患者易发生YMDD自然变异，而HBVDNA定量低于105copies／ml的CHB患者不易发生YMDD自然变异。CHB患者的性别、HBeAg和抗一HBe状态及肝功能损害程度与YMDD自然变异无关。结论CHB患者中存在HBVYMDD自然变异，低龄和HBVDNA高值的患者易发生YMDD自然变异；自然变异与患者性别、HBeAg和抗一HBe状态及肝功能损害程度无关。

Spontaneous YMDD mutation in patients with Chronic hepatitis B

Objective To investigate the possible mechanism of spontaneous HBV YMDD mutation observing the clinical characteristics of chronic hepatitis B （CHB）and provide new ideas for antiviral therapy of CHB. Methods 144 HBV DNA positive CHB cases no antiviral therapy were observed. HBV YMDD mutations were detected by PCR melting curve method and some experimental indexes, for example, HBV DNA quantitative analysis, serum alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, and antigens/antibodies of HBV （including HBsAg, HBsAb, HBeAg, HBeAb and HBcAb）, were also determined. Statistical analysis of these experimental data and information of these cases such as age and gender were performed. Results 30 cases with spontaneous HBV YMDD mutation, of which 19 （63.3%） was YIDD positive, 8（26.7%） YVDD positive, and 3（10.0%） YIDD and YVDD positive, were found out among 144 subjects. Age of the group with spontaneous HBV YMDD mutation was significantly lower than that of those with non-mutation. The frequency of spontaneous HBV YMDD mutation was obviously high when HBV DNA are above 105 copies/ml in body. However, occurrence of spontaneous HBV YMDD mutation had nothing to do with gender, HBeAg, HBeAb or liver function damage. Conclusions There are spontaneous HBV YMDD mutation in patients with CHB, especially younger patients and patients high HBV DNA copies. And occurrence of spontaneous HBV YMDD mutation doesn＇ t correlate with gender, HBeAg, HBeAb or liver function damage.