YMDD变异患者病情进展的临床观察

Clinical observation on the patients with YMDD mutation

目的:探讨服用拉米夫定YMDD变异者病情进展相关因素,提高抗HBV的治疗效果。方法:选择接受拉米夫定治疗患者267例,平均治疗18个月后进行YMDD检测,分成YMDD(+)组、YMDD(-)组,分析两组间在治疗前1个月、平均治疗18个月后肝功能、血清学肝纤维化、HBV-DNA定量的差异。结果:YMDD(+)组与YMDD(-)组比较,治疗前YMDD(-)组HBV-DNA病毒量普遍较YMDD(+)组低;患者在治疗后YMDD(+)组转氨酶、HA、IVC明显高于YMDD(-)组(P<0.05);蛋白合成指标(TP、Alb)均低于YMDD(-)组(P<0.043);HBV-DNA阳性率明显高于YMDD(-)组。结论:拉米夫定治疗后转氨酶、肝纤维化指标升高、蛋白合成指标下降,HBV-DNA病毒增加应作为YMDD变异患者病情进展的临床指标。HBV-DNA定量较低,ALT较高抗病毒效果较好,发生变异几率较低。

Objective To explore the possible factors in affecting the prognosis of the lamivudine-treated patients with YMDD mutation and improve the efficacy of anti HBV treatment. Methods After 18 months of oral lamivudine treatment （ 100mg/d）, 267 patients with chronic hepatitis B were assigned to the YMDD（ ＋ ） group and the YMDD（- ） group based on emergence of the YMDD mutation. Their liver functions, serum fibrosis markers and HBV-DNA levels were measured before the treatment and the measurement was repeated after the treatment for 18 months to evaluate the potential factors in affecting the prognosis of the disease. Results The HBV-DNA level in the YMDD（ - ）group was generally lower than that in the YMDD（ ＋ ） group before the lamivudine treatment. After 18 months of the treatment, the levels of ALT/AST, HA, and IVC in the YMDD （ ＋ ） group were obviously higher than those in the YMDD（ - ） group （ P 〈 0. 05）, whereas the levels of TP and Alb were obviously decreased （ P 〈 0. 043） and the positive rate of HBV-DNA was markedly higher. Conclusions The elevated levels of ALT/AST, serum fibrosis markers, and HBV-DNA as well as the lower levels of TP and Alb during lamivudine treatment can be used as the clinical indexes for the prognosis of the patients with YMDD mutation. The efficacy of anti HBV treatment may be better and the mutation rate is decreased under the lower HBV-DNA level but higher ALT level.